Article

Diagnostic Value of HLA-B27 Testing in Ankylosing Spondylitis and Reiter's Syndrome

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Abstract

Typing for histocompatibility antigen (HLA)-B27 has been suggested as a clinically valuable diagnostic test for ankylosing spondylitis and Reiter's syndrome, although some decry its use for this purpose. Diagnoses can be made in most patients with these diseases on the basis of the history, physical examination, and roentgenographic findings. The B27 test cannot be used to screen an asymptomatic population to detect these diseases and should not be thought of as a routine diagnostic test. We present probability graphs derived from Bayes' theorem, which show that for certain patients the B27 test, when used properly, is of clinical value as an aid to diagnosis. Proper application of the B27 test in clinical medicine is discussed. The test result does not absolutely confirm or exclude the presence of these diseases; it merely provides a probability statement on their existence in the patient. The test is therefore most useful to physicians who understand the use of probability reasoning in clinical decision making.

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... Thus, while it is not a good test for the screening of AS in community or population due to low post-test probability (false positivity among those without clinical features of inflammatory back pain), it is a highly useful test among those with clinical features of inflammatory back pain (having high pre-test probability). 3,4 Over the years rheumatologists have evolved clinical instruments for recognizing inflammatory back pain including Calin, Berlin criteria, Assessment of Ankylosing Spondylitis (ASAS) group and the most recent Weisman criteria [discussed in refs 1, 2], and have become proficient in its recognition. Therefore, low back pain patients evaluated by rheumatologists automatically fall in the high-pre-test probability group, thus making HLA-B27 test a highly sensitive and specific diagnostic test. ...
... Realizing the importance of HLA-B27 in the diagnosis of AS, the ASAS group has recommended its use in the algorithmic approach for diagnosing these conditions. 1 The role of HLA-B27 in the diagnosis of this group of conditions has been discussed extensively elsewhere. 3,4 Under these circumstances, the reliability of the results for HLA-B27 gene screen becomes crucial. ...
... Such advance case selection to augment the number of defective hearing cases effectively alters the base rate for the deficit relative to the population at large. This artificially inflates the observed correlations and measures of sensitivity and specificity (see Griner, Mayewski, Mushlin, & Greenland, 1981, for a discussion of this problem, and Khan &Khan, 1982, andWatson &Tang, 1980, for applied examples). For this reason, subjects were not pre-selected on the basis of previous hearing tests. ...
... Such advance case selection to augment the number of defective hearing cases effectively alters the base rate for the deficit relative to the population at large. This artificially inflates the observed correlations and measures of sensitivity and specificity (see Griner, Mayewski, Mushlin, & Greenland, 1981, for a discussion of this problem, and Khan &Khan, 1982, andWatson &Tang, 1980, for applied examples). For this reason, subjects were not pre-selected on the basis of previous hearing tests. ...
Article
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Previous attempts to assess hearing loss by means of self-report survey items have shown only low to moderate correlations with actual audiometric measures, probably because these attempts used items with high face validity rather than laboratory-tested validity. Beginning with a pool of 108 items used with 384 individuals, we developed a self-report inventory (see Appendix) suitable for group testing or survey administration, which appears to have high correlation with pure-tone hearing thresholds. The inventory was then cross-validated against laboratory audiometric measures in a separate sample of 422 subjects. The resulting 12-item Hearing Screening Inventory (HSI) was shown to be reliable with an internal consistency coefficient (alpha) of 0.89 and test-retest stability coefficient of 0.88. The correlation between pure-tone hearing thresholds in the better ear and the HSI scores for the combined samples was r = 0.81. The correct classification rate for the HSI was 92.1% for a low fence of 25-dB hearing level and 93.4% for a high fence of 55-dB hearing level. A conversion equation with estimated variability is also provided for point estimates of pure-tone hearing thresholds from the HSI scores. A copy of the inventory and scoring procedure is appended to this report.
... Pathogens commonly associated with Reiter's syndrome are Shigella, Salmonella, Yersinia, Campylobacter, Amoeba and Chlamydia. 1 The estimated incidence of Reiter's syndrome is approximately 4/1000 per year. 8 The genetic predisposition to Reiter's syndrome is well established. Eighty percent of patients are positive to HLA-B27 compared to 6% of normal occasions 1,7 . ...
... Other manifestations may include fever, prodromal symptoms, rheumatology lesions, and gastrointestinal and cardiac involvement 10 . Reiter's syndrome could be incomplete when there is no evidence of enteric or urethral inflammation 8 . Clinical assessment was done by taking full history and doing careful physical examination. ...
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Objective: To study the epidemiological and clinical features of Reiter's syndrome in patients who visited the rheumatology clinic in King Hussein Medical Centre (KHMC), Jordan. Methods: A prospective study, including 43 patients with the diagnosis of Reiter's syndrome was done. Patients were assessed by taking complete history, physical examination and appropriate investigations including urinalysis and culture, stool examination and culture, synovial fluid analysis, complement fixation test for chlamydia trachomatis, complete blood count, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibodies, HLA-B27 and radiological study. Results: All patients in this study were white men, with mean age of 26.3 years. HLA-B27 was positive in 37 patients (86%). Most cases were post venereal (32 patients, 74%) while the rest were dysenteric. The clinical manifestations were arthritis in all patients (100%), urethritis in 21 patients (48%), ocular involvement in 20 patients (46%), diarrhoea in 12 patients (28%), painless oral ulcers in 11 patients (26%), skin lesions in 5 patients (12%) and constitutional symptoms in 7 patients (16%). Arthritis was mostly oligoarticular (25 patients, 58%) with asymmetrical pattern in 34 patients (78%). Large joints of lower extremity were most involved (29 patients, 68%). Rheumatoid factor and antinuclear antibodies were negative in all patients. Relapses occurred in 7 patients (16%) after a mean period of 6.2 months. Conclusion: It is concluded that the epidemiological and clinical features of Reiter's syndrome in Jordan are not different from those in the literature.
... The difference between groups regarding HLA-B27 status was to be expected, because frequencies of HLA-B27 vary sharply among the various forms of SpA and among different ethnic groups 5,30 . For example, in healthy individuals, the frequency of HLA-B27 in American blacks ranges from 2% to 4%; in Mexican mestizos it varies between 2% and 5% 31,32 ; in Colombia the percentage is under 1% 33 ; and in whites it is 8%. ...
... Serologic testing is most useful if the pretest probability is ^4096-6096, for example, a patient with unspecified arthritis, who does not recall having had EM but has a history of meningitis or neuritis of unknown etiology before onset of joint symptoms [32,33]. It cannot be emphasized too strongly that serologic results must be interpreted with caution; the physician must beware of false-negative and, more commonly, false-positive results [6]. ...
Article
A past history of clinical Lyme borreliosis and the 6-month incidence of clinical and asymptomatic Lyme borreliosis was studied prospectively in a high-risk population. In the spring, blood samples were drawn from 950 Swiss orienteers, who also answered a questionnaire. IgG anti-Borrelia burgdorferi antibodies were detected by ELISA. Positive IgG antibodies were seen in 248 (26.1%), in contrast to 3.9%–6.0% in two groups of controls (n = 101). Of the orienteers, 1.9%–3.1% had a past history of definite or probable clinical Lyme borreliosis. Six months later a second blood sample was obtained from 755 participants, 558 (73.9%) of whom were seronegative initially; 45 (8.1%) had sero converted from negative to positive. Only 1 (2.2%) developed clinical Lyme borreliosis, Among all participants, the 6-month incidence of clinical Lyme borreliosis was 0.8% (6/755) but was much higher (8.1%) for asymptomatic seroconversion (45/558). In conclusion, positive Lyme serology was common in Swiss orienteers, but clinical disease occurred infrequently.
... Devido a isso, o teste para HLA-B27 deve ser considerado especialmente nos pacientes que apresentem dor infl amatória na coluna, pois esses pacientes apresentam maior probabilidade de defi nição de um diagnóstico. 32 A doença apresenta manifestações: 1) Sistêmicas A apresentação clássica tem início com dor infl amatória na coluna, de forma insidiosa, com rigidez matinal e melhora com exercício, piorando com repouso ou inatividade. Outras manifestações das espondiloartrites soronegativas incluem astenia, fadiga, emagrecimento leve, febrícula. ...
Article
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The present article reviews the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of ankylosing spondylitis and its association with ocular changes. The authors used the PubMed (MEDLINE), LILACS, and Ophthalmology Library databases. Ankylosing spondylitis is a chronic inflammatory disease that usually affects the axial skeleton and can progress to stiffness and progressive functional limitation. Ankylosing spondylitis usually begins around the second to third decade of life, preferentially in HLA-B27-positive white males. Its etiology and pathogenesis are not completely understood, and its diagnosis is diffi cult. Clinical control and treatment are frequently satisfactory. Acute anterior uveíte is the most common extra-articular manifestation, occurring in 20%-30% of the patients with ankylosing spondylitis. Approximately half of the acute anterior uveíte cases are associated with the presence of the HLA-B27 antigen. It can be the first manifestation of an undiagnosed rheumatic disease, usually having a good prognosis and appropriate response to treatment. In conclusion, for better assessment and treatment of patients with uveitis, ophthalmologists and rheumatologists should work together.
... Finally we have no data on the frequency of HLA B-27 in our population or our patients. However, in most adult patients, AS can be diagnosed using clinical criteria without HLA-B27 information (35). Moreover, diagnostic criteria for AS are nearly the same, irrespective of information on HLA-B27 (7, 23). ...
Article
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To evaluate the incidence and prevalence of ankylosing spondylitis (AS) in southern Albania and to assess the association of various demographic risk factors with the severity of disease. This is an observational study with cross-sectional analyses, conducted in the region of Gjirokaster, between 1995 until 2011. The diagnosis of AS was based on the modified New York criteria. Data on population are obtained from the reports of the National Institute of Statistics. Between 1995 and 2011, there were 54 patients diagnosed with AS. Of them, 48 subjects were males (88.9%) and 6 subjects females (11.1%). The AS prevalence in adult population (≥14 years of age), in December 2010, was 0.061%. The 5-year incidence (2006-2010) in adult population was 0.006 %. The mean age at the onset of disease was 29.7±8.4 years. The mean age in 2011 (n=50 subjects) was 51.6±12.7 years. The duration of the disease was 22.7±11.2 years. More than two thirds of the patients (70.3%) were in the advanced radiological stages of the disease. A younger age at the onset of the disease, longer delay in diagnosis, lower educational level and smoking were significant independent factors associated with the advanced forms of the disease. In southern Albania, the AS prevalence in 2010 was 0.061% and the 5-year incidence (2006-2010) was 6 new cases per 105 adults. The incidence and prevalence of AS in Southern Albania are close to the respective regional epidemiological data.
... Concerning the association SSAs with positive tests for HLA-B27, most people who have a positive test do not have these diseases, and some patients who do have one of the SSA diseases have negative tests for HLA-B27. Thus, this test cannot exclude or confirm these diseases [18]. But the patients with positive HLA-B27 have more severe and acute disease [19]. ...
Article
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Spine involvement is less common in Reiter's syndrome than in other seronegative spondyloarthropathies. Also, cervical spine involvement rarely occurs in Reiter's syndrome and other spondyloarthropathies. This paper reports a rare case of Reiter's syndrome in which there was cervical spine involvement that presented clinically as an atlanto-axial rotatory subluxation. Reiter's Syndrome (RS) is one of the most common types of seronegative spondyloarthropathies (SSAs) that presents clinically with a triad of symptoms, i.e., conjunctivitis, urethritis, and arthritis. This case highlighted the importance of radiographs of the lateral cervical spine and dynamic cervical imaging for all patients who have Reiter's syndrome with cervical spine symptoms to ensure that this dangerous abnormality is not overlooked.
... VOL. 12 No. 3 -2005 radiológicos, sin necesidad de ordenar una prueba de HLA B27 5,129,130 . ...
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Resumen Las espondiloartropatías son un grupo de enfer-medades inflamatorias crónicas, de las cuales se des-tacan especialmente la espondilitis anquilosante, artritis reactiva, artritis psoriásica, artritis asocia-da con la enfermedad inflamatoria intestinal y las espondiloartropatías indiferenciadas. Los subgrupos más comunes de espondiloartropatías son la espondilitis anquilosante y la espondiloartropatía indiferenciada. El diagnóstico de la espondilitis anquilosante se basa especialmente en los hallazgos radiológicos inequívocos de sacroiliítis de grado 2 bilateralmente o grado 3 unilateralmente. Sin em-bargo en la fase temprana de la enfermedad, los es-tudios radiológicos no son lo suficientemente sensibles como para mostrar la presencia de sacroiliítis y por lo general pueden tardar varios años para detectar la presencia de sacroiliitis radiológica; de esta ma-nera el diagnóstico de espondilitis anquilosante pue-de tardar hasta 8 a 11 años luego del inicio de los síntomas; como consecuencia de ello, el diagnóstico de espondiloartropatía con compromiso axial en au-sencia de sacroiliítis radiológica es de gran dificul-tad para el reumatólogo. En los estadíos tempranos, el test de HLA B27 y la resonancia magnética de articulaciones sacroiliacas son útiles en el diagnósti-co temprano. En presencia de dolor crónico de es-palda la probabilidad de espondiloartropatía axial es de un 5% y aumenta a un 14% en presencia de dolor de espalda inflamatorio; la probabilidad de espondiloartropatía axial aumenta a un 90% en pre-sencia de = 3 hallazgos de espondiloartropatías (talagia, uveítis, dactilitis, historia familiar positiva, dolor glúteo alternante, psoriasis, enfermedad inflamatoria intestinal, artritis asimétrica, respues-ta favorable a los antiinflamatorios no esteroideos). De otra parte, la positividad del HLA B27 y la reso-nancia magnética aumentan la probabilidad de la en-fermedad, en especial en aquellos casos que no presentan otros hallazgos de espondiloartropatías o que presentan 1 a 2 manifestaciones de espondilo-artropatías. En pacientes con espondiloartropatía psoriásica o asociada con la enfermedad inflamatoria intestinal el uso del HLA B27 es de valor limitado, ya que estas entidades por lo general tienen una aso-ciación negativa con el HLA B27. También se debe tener en cuenta, que la utilidad del HLA B27 y sus diferentes subtipos difiere entre los diferentes gru-pos étnicos y su valor en el diagnóstico depende de la probabilidad pre-test individual de cada caso. Palabras Clave: espondiloartropatías seronega-tivas, espondilitis anquilosante, diagnostico temprano.
... [12] Sclerosis and obliteration of the joint space, ligamentous calcification, squaring of the vertebrae, and in end stage disease, the characteristic ankylosed "bamboo" spine can be seen on plain radiography. It is noteworthy that seropositivity is neither necessary nor sufficient for establishing the diagnosis of AS. [13] Establishing the diagnosis of AS relies on a thorough history and physical examination besides radiologic confirmation. The disease should not be ruled out if the aforementioned criteria are not met. ...
Article
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The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn’s disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral nongranulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF- α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of undertreatment.
... 44 This is similar to recommendations made for B27 testing in the spondyloarthropathies. 55 Testing is best directed by a careful and thorough patient history and physical exam and the identification of certain key clinical features should direct testing for HLA-B27. ...
Article
Acute anterior uveitis is generally recognized as the most common form of uveitis. An association with HLA-B27 is seen in approximately half of cases of acute anterior uveitis. The prevalence of HLA-B27 varies widely between ethnic populations, with an approximate 8-10% prevalence in non-Hispanic whites and lower prevalence in Mexican- (4%) and African- (2-4%) Americans. A group of systemic inflammatory diseases, the spondyloarthropathies, similarly demonstrates a strong association with HLA-B27. The strength of association varies, depending on the specific spondyloarthropathy, with the strongest association found in patients with ankylosing spondylitis. The majority of patients with HLA-B27 associated uveitis will have an underlying spondyloarthropathy. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history to assess for features of a spondyloarthropathy as the characteristics of any associated uveitis may vary.
... Beginning with a clinical estimate of the likelihood of ankylosing spondylitis or a related spondarthropathy, Bayes' theorem can be used to calculate the probability that a patient has the disease, depending on whether they transpire to be HLA-B27 positive or negative. 41 The usefulness of a positive result will be greatest in populations, such as the Japanese, that have a low general prevalence of HLA-B27 and yet its association with ankylosing spondylitis is strong. For the other spondarthritides, which are less strongly linked with HLA-B27, diagnosis is based primarily on the associated clinical features. ...
... This assessment has no additional value in established disease or as a pure screening tool. [4] However in young patients with inflammatory chronic back pain, a positive HLA-B27 test increases the likelihood of having AS particularly if imaging of the sacroiliac joints does not provide conclusive results. A normal erythrocyte sedimentation rate (ESR) or normal C-reactive protein level does not exclude active disease. ...
... Other common alleles reported from India are HLA-B*27:07, HLA-B*27:02, and HLA-B*27:10, all of which have been documented to be associated with AS. [7][8][9][10][11][12] Serological techniques such as microcytotoxicity and flow cytometry for testing HLA-B27 require viable cells that adequately express HLA-B27 and may give false negative results if HLA-B27 is downregulated or "masked". 13 Flow cytometry, a widely used technique in India, is rapid, high-throughput and relatively inexpensive but has been reported to lack specificity, especially in the presence of antigens that cross-react with HLA-B27, such as HLA-B7 and HLA-B37. ...
Article
Background: Determination of HLA-B27 status plays an important role as adjuvant in suspected cases for diagnosis of Ankylosing Spondilytis (AS). Objectives of this study were to evaluate (i) flow cytometry method in comparison with DNA microarray for HLA-B27 typing and (ii) EUROArray HLA-B27 Direct assay for HLA-B27 allele detection along with discrimination of AS/non-AS subtypes in Indian population. Methods: A total of 7543 patients with a presumptive clinical diagnosis of AS were referred for screening of HLA-B27. All samples were initially tested by flow cytometry, and based on its findings, 1560 samples were analyzed for the presence of HLA-B27 allele by microarray technology. A subset of samples (n = 200) were further tested by DNA sequencing for identification of HLA-B27 subtypes. Results: Screening of HLA-B27 by flow cytometry reported 1551 positive (20.56%) and 5556 negative (73.65%) cases. Remaining 436 (5.78%) samples were identified within equivocal zone. Of cases (n = 1560) analyzed by microarray method, 1333 (85.44%) and 227 (14.55%) were detected microarray positive and negative, respectively. DNA sequencing identified HLA-B*27:07 as the predominant subtype among cases showing ex2 positivity by microarray method. Of 200 cases, 20 cases (14 of HLA-B*07 and 6 of HLA-B*37) of HLA-B27 cross-reactive subtypes were also identified. Conclusion: We recommend DNA typing as a complementary tool along with flow cytometry to accomplish successful HLA-B27 phenotype determination. This is the first study among Indian population to evaluate efficacy of EUROArray to detect B27 allele and its potential to indicate the presence of nondisease-associated alleles in Indian population.
... HLA-B*27 typing has been proposed as a useful test for AS and related spondyloarthropathies (SpA), and thus the availability of a reliable and accurate detection method is important (3). Although the result of HLA-B*27 typing is unable confirm or exclude the diagnosis of this disease (10), different subtypes may be associated with different ethnic groups, clinical manifestation, age of onset and prognosis (11). ...
Article
The association of spondyloarthropathies with different alleles of human leukocyte antigen (HLA) B*27 is well established. Different subtypes of HLA-B*27 may be linked with different ethnic groups, distinct clinical manifestations, specific age of onset and different prognoses. Polymerase chain reaction with sequence specific primers (PCR-SSP) is the most frequently adapted molecular method used for the recognition of HLA-B*27-specific DNA sequences. The aim of the present study was to standarise an in-house protocol of PCR-SSP for HLA-B*27 allele detection for use in the Armed Forces Institute of Pathology (AFIP), Pakistan, with consideration of its cost effectiveness. A total of 49 individual samples were included, comprising 10 transplant samples determined to be HLA-B*27-negative by PCR-SSP and 39 HLA-B*27-positive samples determined by flow cytometry, obtained from patients who were symptomatic and referred for HLA-B*27 testing. By altering each variable individually, an in-house PCR-SSP protocol was optimized to amplify common HLA-B*27 alleles (2701-2721, 2723-2730). To discriminate B*27 from all other HLA-B alleles, a low-resolution HLA-B typing set with a 96 PCR-SSP primer mixture was used in conjunction. Among the 39 HLA-B*27-positive specimens, 31 (79%) were detected as positive by PCR-SSP, with the remaining samples failing due to a sub-optimized protocol and/or low DNA concentration. Additionally, there was complete concordance between flow cytometry and in-house PCR, and the sensitivity and specificity of the PCR-SSP were determined to be 100%. In conclusion, in-house SSP-PCR is, standard method for the detection of HLA-B*27 alleles. The determination of associations between specific HLA-B*27 alleles and AS may aid to identify individuals at higher risk of developing the disease. Furthermore, the identification of individuals at risk may aid to adapt preventive strategies.
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OBJETIVO: Determinar la asociación causal entre parasitosis intestinal y artritis reactiva (ARe). MATERIAL Y MÉTODOS: Estudio de casos y controles. El grupo de casos comprendió 31 pacientes con diagnóstico de ARe internados en el Hospital Militar Central de Lima durante los años 1994-1995. El grupo control abarcó a 31 pacientes sin ARe. La información se recogió de las historias clínicas que correspondían tanto a personal civil como militar. RESULTADOS: En el grupo de casos, 11 pacientes (35,48%) tuvieron parasitosis intestinal; 12 pacientes (38,71%) presentaron eosinofilia que remitió con albendazol y/o metronidazol, con mejoría evidente del cuadro clínico; y 8 pacientes (25,81%) no tuvieron parasitosis ni eosinofilia. En el grupo control la proporción fue 7 (22,58%), 5 (16,13%) y 19 pacientes (61,29%), respectivamente. CONCLUSIÓN: Existe una fuerte asociación entre la exposición a parásitos intestinales y ARe (OR = 4,5; p <0,05), pudiendo existir un sinergismo en el efecto artritogénico debido a poliparasitismo. Los parásitos más frecuentemente hallados fueron Ascaris lumbricoides (7/11) y Ancylostoma duodenale (5/11).
Article
Objective. To determine trends in the incidence and clinical presentation of ankylosing spondylitis first diagnosed between 1935 and 1989 among residents of Rochester, Minnesota, and in the survival of the patients. Methods. Population-based descriptive study. Results. The overall age- and sex-adjusted incidence rate was 7.3 per 100,000 person-years (95% confidence interval 6.1–8.4). The rate tended to decline between 1935 and 1989, but there was little change in the age at symptom onset or diagnosis over the 55-year study period. Overall survival was not decreased up to 28 years following diagnosis. Conclusion. These data indicate that there is a constancy in the epidemiologic characteristics of ankylosing spondylitis and suggest that previously study results indicating changes may have been due to biases in patient selection and study design.
Article
Objective. To evaluate the new magnetic resonance imaging (MRI) method of dynamic MRI with fast imaging in the diagnosis of sacroiliitis among patients with spondylarthropathy. Methods. Fifteen patients with a history of inflammatory back pain without radiographic evidence of grade II or greater sacroiliitis (group 1), 25 patients with definite ankylosing spondylitis (group 2), and 12 patients with noninflammatory spinal pain (controls) (group 3) were examined. Dynamic MRI with fast imaging was performed after intravenous bolus injection of the contrast agent gadolinium—diethylenetriamine pentaacetic acid. The degree of enhancement was graded as representing acute sacroiliitis, latent sacroiliitis, or no sacroiliitis. Results. Acute sacroiliitis was detected in 22 of 30 sacroiliac (SI) joints in group 1 patients and in 27 of 50 SI joints in group 2 patients; latent sacroiliitis was seen in 25 of 80 SI joints in patients from groups 1 and 2. No group 3 patient was found to have sacroiliitis. Conclusion. Early sacroiliitis can be demonstrated by dynamic MRI in spondylarthropathy patients in whom abnormalities are not revealed by conventional radiography.
Chapter
Radiographs and magnetic resonance imaging (MRI) for sacroiliac (SI) joints and the spine are the most important imaging techniques for the diagnosis and followup of patients with spondyloarthritis (SpA), including response to treatment. If other sites outside the axial skeleton are affected they can also be investigated by these methods. In general, radiographs should not be performed more frequently than every 2 years because (chronic) changes occur slowly and investigations with MRI can be used more frequently, according to the clinical situation.
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Diabetes case management and self-care education can effectively improve patient clinical outcomes and quality of life. Diabetes case management should be provided by an interdisciplinary team. Diabetes education has evolved from its previous focus on "teaching proper content" to "achieving successful patient outcomes" in line with the current emphasis in health education on patient-centered goals. Behavioral changes are facilitated based on these goals. Behavioral change directed at successful diabetes self-care was adopted as one of the desired outcomes of diabetes case management. The American Association of Diabetes Educators developed seven diabetes self-care behaviors as behavior objectives and evaluation indicators of diabetes education. These indicators include healthy eating, being active, monitoring, taking medication, problem solving, healthy coping, and reducing risks. The process of diabetes case management includes assessment, expected outcome identification, planning, implementation, evaluation, and documentation. In Taiwan, the Diabetes Share Care Network has promoted the advantages and techniques of diabetes case management. Based on network recommendations, the improvement program of National Health Insurance payment for diabetes medical treatment under the Bureau of National Health Insurance now provides package payment and requires quality interdisciplinary care and case management.
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The most important clinical features of the spondyloarthritides (SpA) are not only inflammatory back pain (IBP) but also peripheral (enthesitis) and extra-articular symptoms. For clinical purposes, two forms related to the predominant clinical manifestation - axial and peripheral SpA - and five subgroups- ankylosing spondylitis (AS), SpA associated with psoriasis and inflammatory bowel disease (IBD), reactive arthritis and undifferentiated SpA - are differentiated. Axial SpA including AS is the most frequent subtype of SpA, followed by psoriatic arthritis and undifferentiated SpA, while reactive arthritis and IBD-related SpA are less frequent. The prevalence of SpA has been shown to be similar to rheumatoid arthritis. The outcome of the disease is influenced by the degree of disease activity over time, which is mainly related not only to inflammation but also on the structural damage (new bone formation) that occurs over time. Treatment options for patients with SpA have been limited for decades. Non-steroidal anti-inflammatory agents are currently considered first choice, since they have shown good amelioration of symptoms in SpA patients especially when suffering by the typical symptom of IBP. Furthermore, there is a clear role for regular physiotherapy in AS to prevent loss of spinal mobility. For patients who have insufficiently responded to conventional therapies, four anti-tumour necrosis factor (TNF) agents are available and are approved for the treatment of patients with active AS: infliximab, etanercept, adalimumab and golimumab. As far as it stands now, TNF blockers seem to have no influence on new bone formation in AS.
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Family studies and investigation of the HLA associations have in recent years added to our understanding of the spondyloarthropathies. In regard to ankylosing spondylitis it is likely that B27 itself is the major susceptibility gene but that additional genes may play a secondary role. Heterogeneity of the B27 antigen has been demonstrated but has not yet been shown to be relevant to disease susceptibility. Haplotypes including Cw6 are related to susceptibility to psoriasis and psoriatic arthritis and although the risk for the arthropathy is increased in B27-positive individuals, there is some uncertainty regarding the association with other B locus antigens and further work is needed. There is also uncertainty as to whether B27-associated disorders occur randomly within families, or whether particular disorders cluster in certain families and further evidence in this field would be of considerable interest. Genetic studies, as here outlined, have not as yet had a major impact in clinical medicine but it is anticipated that a deeper understanding of the mechanisms of HLA-linked susceptibility genes and in particular of how they interact with environmental agents, will improve our ability to treat and possibly prevent the relevant diseases.
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To determine trends in the incidence and clinical presentation of ankylosing spondylitis first diagnosed between 1935 and 1989 among residents of Rochester, Minnesota, and in the survival of the patients. Population-based descriptive study. The overall age- and sex-adjusted incidence rate was 7.3 per 100,000 person-years (95% confidence interval 6.1-8.4). The rate tended to decline between 1935 and 1989, but there was little change in the age at symptom onset or diagnosis over the 55-year study period. Overall survival was not decreased up to 28 years following diagnosis. These data indicate that there is a constancy in the epidemiologic characteristics of ankylosing spondylitis and suggest that previously study results indicating changes may have been due to biases in patient selection and study design.
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AND PERSPECTIVES The frequency of uSpA has been ignored in previous epidemiologic studies because of the inadequacy of the existing classification criteria. With the use of the recently developed ESSG criteria,29a the real prevalence may be better defined in the future and may also lead to early recognition of such patients in clinical practice. But even more challenging is the issue to elucidate the suspected infectious etiology in most patients with uSpA. Extensive microbiologic diagnostic investigations and the use of new molecular biologic methods for detecting microbes or microbial antigens will advance our understanding over the next years. The term uSpA is only a working label with the implicit demand to solve these clinical conundra by follow-up or even better by identifying the causative or triggering agents.
Article
A review of the literature regarding computer-assisted diagnosis of rheumatic diseases is presented. After a general outline of the history and goals of computer programs intended to support physicians in the diagnostic process, 14 systems or projects are described. The scope of seven of these is general internal medicine, and the other seven are intended exclusively for rheumatic problems. The majority of these systems are prototypes. To date, none of them is widely used by physicians. Preliminary evaluation studies and/or independent reviews have been reported for all of the systems. The need for further evaluation studies is recognized, and strategies to carry these out are outlined. Furthermore, the potential usefulness for patient care and education is discussed. It is concluded that a new and interesting field is being developed that deserves more attention among rheumatologists.
Article
Despite impressive advances in our understanding of the natural history of the rheumatic diseases and their treatments, there remains much to be learned. The management of most of these diseases is far from satisfactory for either the clinician or patient. There is little distinction between clinical practice and clinical research. How much and what type of data one should collect clearly depends on the setting and on the clinical/research questions being asked. One must ensure that the literature is relevant to his or her practice. The corollary is that research must be derived from a variety of settings, including both the traditional researcher and the traditional clinician.
Article
Ankylosing spondylitis and related spondyloarthropathies show a remarkable association with a genetic marker--HLA-B27--and also illustrate the relationship between host and environmental factors. HLA-B27 has revitalized the epidemiology of spondyloarthropathies and has helped to broaden the clinical spectrum of these diseases. These and other aspects of descriptive and genetic epidemiology are reviewed.
The informational indices comprise sensitivity, specificity and predictive value, and they give information on the probability of rheumatic disease being present or not. It is interesting that in clinical situations where the probability of the disease is appraised by the physician before the test, the probabilities may be strongly modified after the test. For example, if one estimates the pre-test probability of ankylosing spondylitis at 50% in a given patient, the HLA B27 antigen test will modify the probability of the disease as follows: B27 positive: probability 90% B27 negative: probability 7% The second part of the study discusses modern methods for the validation of diagnostic criteria and assessment tests. Validation of the latter includes inter- and intra-observer reproducibility, coefficient of variation, discriminating power of each assessment test in a double-blind "reverse" trial, in which the difference between placebo and active drug is the known base, the value of the tests being the unknown.
Article
Objective To determine the overall prevalence of spondylarthropathy (SpA) among whites.Methods To screen for SpA symptoms, such as inflammatory back pain (IBP), joint swelling, psoriasis, and uveitis, or a specific family history, questionnaires were mailed to 348 blood donors (174 HLA-B27 positive and 174 HLA-B27 negative). From the responding 273 persons (78%; 140 B27 positive, 133 B27 negative), 126 were selected for further evaluation based on the symptoms reported. Of this group, 90 persons agreed to undergo physical examination (71.4%; 46 B27 positive, 44 B27 negative). There was no difference between the B27-positive and -negative groups in terms of age (mean ± SD 38.4 ± 10 versus 39.5 ± 11 years) and sex ratio (67% versus 68% were men). In addition, 58 donors (32 B27 positive, 26 B27 negative) agreed to undergo magnetic resonance imaging (MRI) of the sacroiliac joints. A diagnosis of SpA and ankylosing spondylitis (AS) was made according to the European Spondylarthropathy Study Group criteria and the New York criteria.ResultsSpA was diagnosed in 20 persons: 19 of 140 B27-positive (13.6%) and 1 of 133 B27-negative (0.7%) subjects (15 male and 5 female). AS was diagnosed in 9 persons (7 male and 2 female; 45%), undifferentiated SpA (USpA) in 7 (5 male and 2 female; 35%), psoriatic arthritis (PsA) in 3 (2 male and 1 female; 15%), and chronic reactive arthritis (ReA; Reiter's syndrome) in 1 (male; 5%). On the basis of a B27 frequency of 9.3% among the population of Berlin (3.47 million persons), the estimated prevalence of SpA was 1.9%, AS was 0.86%, USpA was 0.67%, and PsA was 0.29%. The relative risk of developing SpA in B27-positive subjects was calculated as 20.7 (95% confidence interval 4.6-94.2; P = 0.001). Of 58 persons with IBP, sacroiliitis was detected by MRI in 15 of 32 B27-positive (46.9%) and 1 of 26 B27-negative (3.9%) subjects (P = 0.002). Four of these 16 donors did not fulfill diagnostic criteria for SpA.Conclusion With a calculated prevalence of 1.9%, spondylarthropathies are among the most frequent rheumatic diseases in the white population. HLA-B27 positive persons carry a 20-fold increased risk of developing SpA. AS and USpA are the most frequent SpA subtypes. Persons with IBP who are B27 positive have a 50% likelihood of having sacroiliitis.
Article
Full-text available
Objective: To compare the clinical, demographic, and serologic characteristics and the treatment of patients diagnosed with ankylosing spondylitis (AS) from Europe (EU) and Latin America (LA). Methods: We included 3439 patients from national registries: the Spanish Registry of Spondyloarthritis (REGISPONSER), the Belgian registry (ASPECT), and the Latin American Registry of Spondyloarthropathies (RESPONDIA). We selected patients with diagnosis of AS who met the modified New York classification criteria. Demographic, clinical, disease activity, functional, and metrological measurement data were recorded. Current treatment was recorded. The population was classified into 2 groups: patients with disease duration < 10 years and those with disease duration ≥ 10 years. A descriptive and comparative analysis of variables of both groups was carried out. Results: There were 2356 patients in EU group and 1083 in LA group. Prevalence of HLA-B27 was 71% in LA group and 83% in EU group (p < 0.001). We found a greater frequency of peripheral arthritis and enthesitis (p < 0.001) in the LA population; prevalence of arthritis was 57% in LA and 42% in EU, and for enthesitis, 54% and 38%. Except for treatment with anti-tumor necrosis factor (anti-TNF), the use of nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, and disease-modifying antirheumatic drugs (DMARD), and the association of anti-TNF and methotrexate use showed a significant difference (p < 0.001) in the 2 populations. Conclusion: The principal differences in the clinical manifestations of patients with AS from EU and LA were the greater frequency of peripheral arthritis and enthesitis in LA group, the higher percentage of HLA-B27 in EU group, and the form of treatment, with a greater use of NSAID, steroids, and DMARD in the LA group.
Article
The end of this century and the dawn of the new millennium are near, and we still don't fully understand the mechanism behind the remarkable association of HLA-B27 with spondy-loarthropathies, although it has been known for more than a quarter of a century. However, there has been a slow but steady progress in the field of spondyloarthropathies. Not all alleles that encode for the HLA-B27 serologic specificity are associated with susceptibility to develop a spondyloarthropathy. The number of known subtypes of HLA-B27 continue to grow; the latest three additions are HLA-B*2713, HLA-B*2714, and HLA-B*2715. It is becoming increasingly clear that the observed synovial and cartilage changes in spondyloarthropathies are mainly the result of an entheseal- rather than a synovial-based pathology, because the initial or primary inflammatory response is located at the enthesis, whereas synovitis is most likely triggered secondarily by locally released cytokines at the adjacent sites in the joint cavity. But we still don't know how ankylosis relates to HLA-B27. The conditions favoring the development of HIV-associated spondyloarthropathy are becoming less of a problem in North America, but this is not the case in some of the other regions of the world, such as Sub-Saharan Africa.
Article
This new companion to Office Orthopedics for Primary Care, 3rd Edition, provides straightforward, in-depth, full-color guidance on the diagnosis of 52 of the most common musculoskeletal problems seen in todays clinical settings. It spells out exactly what to look for during the physical examination and in what sequence, providing readers with the knowledge they need to effectively diagnose these problems. Lavish, full-color photographs and line drawings enhance the text and make concepts easier to understand. Features the expertise of Dr. Bruce Carl Anderson, a world authority on orthopedic practice in primary care. Presents proven how-tos of diagnosis for the 52 most common orthopedic problems. Features detailed descriptions and lavish illustrationswith hundreds of color photographsto show every aspect of proper diagnosis. Provides comprehensive treatment reference tables that list best-practice treatments, procedures, and equipment, such as supports, braces, and casts. Gives cross-references to the companion volume, Office Orthopedics for Primary Care, 3rd Edition. Includes many at-a-glance tables showing diagnostic tips and features, clinical pearls, and differential diagnoses.
Chapter
Die entzündlich-rheumatischen Erkrankungen manifestieren sich als „Rheuma“ am Stütz- und Bewegungssystem und knüpfen insoweit an das vorige Kapitel an. Gemeinsam ist ihnen ein immunologischer Prozess, der zahlreiche weitere Organe mit einbeziehen kann, was das Spektrum möglicher Krankheitserscheinungen und folgen beträchtlich erweitert.
Chapter
Saint-Hillier et al.1 typed 7 French patients for A and B loci antigens. When compared with a control population of unknown size, they found no significant difference between the 2 groups.
Article
Study of products of genes present on a region on chromosome 6 known as the Major Histocompatibility Complex (MHC) is providing new insight into many chronic diseases of undetermined aetiology, including rheumatic diseases such as ankylosing spondylitis1,2 and rheumatoid arthritis3,4. The human MHC is called HLA, and it contains a tightly linked cluster of genes that encode for cell surface glycoprotein molecules expressed on the cell membrane of virtually all cells5–7. These molecules are involved in cell-to-cell interaction and have been subdivided into two distinct groups called class I and class II molecules6–8. The class I molecules are encoded by the HLA-A, -B, and -C loci of the MHC. These molecules display an exceptional degree of genetic polymorphism and are composed of an MHC-encoded heavy — or α — chain that is non-covalently bound to β2-microglobulin, a smaller and invariant polypeptide chain encoded by a gene located on another chromosome5–8. The class II molecules consist of two glycoprotein chains as well, the larger of the two chains is called α chain and the smaller one is called β chain. These two chains are closer in size than those of the class I molecules. Moreover, both α and β chains are encoded by genes located in the HLA-D region7,8.
Article
Ankylosing spondylitis (AS), a prototype of spondyloarthritis (SpA), is a chronic inflammatory disease involving spine, peripheral joints and peri-articular soft tissues. The spectrum of SpA can be classified to 5 diseases categories: ankylosing spondylitis, psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel diseases-associated arthritis, and undifferentiated spondyloarthritis (USpA). Common clinical features of SpA are chronic inflammatory arthritis over spine, sacroiliac joints, peripheral joints and enthesitis. Up to 45% of AS patients may have extra-articular manifestations, such as uveitis, psoriasis, bowel inflammation and nephropathy. The etiology is unknown, but probably related to genetics and immune dysregulation that was triggered by environmental factors, mainly infection and trauma. Management of AS are focused on control of chronic inflammation by non-steroidal anti-inflammatory drugs (NSAID), disease-modifying anti-rheumatic drugs (DMARD) and anti-tumor necrosis factor biological agents.
Article
The association between HLA-B27 and AS was first established in the early 1970s. Since then, our understanding of this disease has changed, such that we now recognize AS to be the extreme of the clinical phenotype within a disease spectrum known as axial SpA (axSpA). Recent advances in therapeutic options have driven the need for earlier diagnosis and many screening strategies have been proposed to facilitate this. In parallel, our understanding of axSpA genetics, and especially the contribution of HLA-B27, has expanded. In this article we will present and discuss the evidence supporting the use of HLA-B27 in clinical practice. We will briefly summarize the evolution of the concept of axSpA, the prevalence of HLA-B27 and axSpA and the potential role of HLA-B27 in the aetiopathogenesis of axSpA and focus on the utility of HLA-B27 in everyday clinical practice.
Chapter
Der Leser wird nach der Lektüre dieses Beitrags Kenntnisse über die Infektätiologie der reaktiven Arthritis sowie die gegenwärtig bekannten Erreger ebenso besitzen wie über die heute gängigen pathogenetischen Hypothesen, die klinische Präsentation, den klinischen Verlauf und die gegenwärtig empfohlenen therapeutischen Maßnah-men. Besonderes Augenmerk wird dabei auf die möglichst frühe Diagnose und kom-plette diagnostische Abklärung zur Optimierung therapeutischer Maßnahmen und damit Verbesserung der Prognose gelegt.
Article
Objectif – Explorer les zones d’incertitude des recommandations HAS, concernant la place du groupage HLAB27, dans le diagnostic de Spondylarthrite axiale. Méthodes – La procédure était la suivante : choix de la question, par un comité scientifique, selon la méthode Delphi ; revue systématique de la littérature, à partir de la base de données PubMed, jusqu’en avril 2011 ; présentation des résultats à un panel d’experts en Rhumatologie et discussion des résultats. Résultats – La recherche bibliographique a permis d’identifier 489 références dont 19 ont servi de base de travail. L’analyse a montré : une discordance entre les spécificités et valeurs prédictives issues des 9 cohortes transversales et celles issues des 4 études prospectives ; une bonne valeur prédictive négative dans les formes axiales ; un apport moindre dans les formes indifférenciées ; un risque de récurrence de Spondylarthrite axiale, chez les apparentés au premier degré, d’environ 8%, majoré à 20% si le sujet est porteur de l’antigène HLAB27 et à 60% s’il s’agit d’un co-jumeau monozygote HLAB27+. Conclusion – Utilisé seul, le groupage HLA est insuffisant pour établir quel patient répondra aux critères de classification d’une spondylarthrite. Son utilisation s’entend plutôt au sein d’un algorithme diagnostique (Berlin) ou de critères diagnostiques (ASAS). Toutefois il semblerait que les performances du groupage HLA utilisé dans ces outils, ont été établies sur des données ne permettant pas de répondre strictement à la question du diagnostic. La valeur diagnostique réelle du groupage HLAB27 doit être précisée dans des études dédiées aux critères ASAS ou à l’algorithme de Berlin.
Article
Associations of HLA antigens with many of the rheumatic diseases have been established over the last two decades. Although these discoveries provide potential new insights into disease pathogenesis, the clinical utility of HLA typing has been limited. The major exception is that of HLA-B27 in the spondyloarthropathies, where clinical uses of HLA-B27 testing has permitted identification of a large spectrum of disease that was previously misdiagnosed and misclassified. HLA-B27 remains potentially useful in the diagnosis of atypical spondyloarthropathies because of its high frequency in patients with these diseases (yielding good sensitivity) and its relatively low frequencies in most normal populations (yielding good specificity). Its predictive value in individual cases, however, depends on the quality of the physician's assessment of the likelihood of a spondyloarthropathy. In patients with juvenile-onset arthritis, typing for HLA-B27, as well as several HLA-class II alleles (DR5, DR8, DP2, and DP3), may prove to be useful in diagnosis and classification; however, additional studies are necessary. HLA oligotyping of DNA in patients with early rheumatoid arthritis to determine homozygosity versus heterozygosity for the DRB1 susceptibility sequence promises a potential new parameter for predicting clinical disease severity, and thus the possible early initiation of more aggressive therapies. Additional studies are necessary, however, to determine the validity of this approach. Finally, the future diagnosis, prevention, and treatments of these diseases may depend on the identification and manipulation of specific immune responses mediated by HLA molecules, thus making HLA typing for clinical purposes routine.
Article
A brief account of current knowledge of the major histocompatability complex (MHC) in man, named HLA, is followed by a review of Class I antigen-associated rheumatic and other autoimmune diseases. Although of great theoretical interest, HLA B27 is of relatively little value as a diagnostic test. It does appear, however, to be more frequently associated with severe disease, and, in ankylosing spondylitis, with certain complications, such as iridocyclitis and cardiac involvement.
Article
OBJECTIVE:Celiac sprue is associated with specific HLA-DQ genes (mainly DQ2). Because there are epidemiological and histopathological similarities between celiac sprue and microscopic colitis, we hypothesized that these syndrome may share an HLA genetic predisposition and pathogenesis.METHODS:The HLA-DQ genes of 25 patients with celiac sprue, 53 patients with the microscopic colitis syndrome, and 429 normal controls were typed and compared. Serum was analyzed for antigliadin and antiendomysial antibodies. Small intestinal biopsies were analyzed for signs of histopathology.RESULTS:HLA-DQ2 or DQ1,3 (the latter as DQ1,7,DQ1,8, or DQ1,9) were seen more frequently in both patient groups relative to controls. In patients with the microscopic colitis syndrome, serological tests for celiac sprue were weakly positive in 17%; mild inflammation of the small intestine without villous atrophy was present in 43%, and inflammation plus partial or subtotal villous atrophy was present in 27%.CONCLUSIONS:A shared set of predisposing HLA-DQ genes account for the epidemiological overlap of celiac sprue and microscopic colitis. Mild to moderate mononuclear cell inflammation of the small intestine, often accompanied by partial or subtotal villous atrophy, is frequent in patients with the microscopic colitis syndrome. Although further studies will be necessary to determine if this enteropathy is induced by dietary gluten, we speculate that the small intestinal but not colonic histopathology in patients with microscopic colitis is caused by immunological gluten sensitivity.
Article
Objectives: The pathogenesis of axial spondyloarthritis (axSpA) is still unclear. There is a strong association with HLA-B27 and other genes. Recently, anti-CD74 antibodies with specificity to a class II-associated invariant chain peptide (anti-CLIP-ABs) were found in axSpA patients. We examined the prevalence, sensitivity and specificity of anti-CLIP-ABs in axSpA in comparison with controls. Methods: Sera of axSpA and non-SpA patients were analysed for IgG-antibodies against CD74 by ELISA with specificity for CLIP developed in cooperation with AESKU Diagnostics (Germany). A cut-off of ≥4 SDs of arbitrary units (AU) from mean serum levels was used to differentiate the results. The laboratory workers were completely blinded for clinical data. Results: We analysed 145 sera from 94 axSpA and 51 non-SpA patients. AxSpA patients were more often male and younger. HLA-B27 status was available in 72 patients. Anti-CLIP-ABs were detected in 85.1% in axSpA but in only 7.8% in non-SpA patients (p≤0.0001). AxSpA patients showed higher levels of anti-CLIP-ABs versus non-SpA: mean 14.5 versus 0.8 AU (p≤0.0001). The sensitivity of anti-CLIP-ABs for diagnosing axSpA was 85.1%, specificity 92.2%, likelihood ratio (LR) LR+ was 10.8 and LR- was 0.08. Anti-CLIP-ABs and HLA-B27 were positive in 87.5% patients with axSpA, but only 14.9% were anti-CLIP-negative, while 23.6% were HLA-B27-negative. Conclusions: Anti-CLIP antibodies were strongly associated with axSpA. The LR for confirming axSpA by using anti-CLIP was even higher than by using HLA-B27. More studies using this promising new method in patients with non-radiographic axial SpA or peripheral SpA are needed to establish its usefulness in clinical practice.
Article
Autoimmune chronic rheumatic inflammatory diseases are polygenic illnesses in which the inflammatory process mainly occurs in the synovial tissue, surrounding the joints. Dozens of inflammatory genes are upregulated or downregulated in each rheumatic disease. The genes of several of the molecules synthesized are often polymorphic and some of these polymorphisms have clearly been shown to be functionally relevant. In recent years monoclonal antibodies directed against some of the molecular targets have been developed, the first ones being the monoclonals against a key driver of synovial inflammation namely tumor necrosis factorα, followed by interleukin 1β, then interleukin 6 receptor and others. According to the background, the clinical benefits could be either partially driven by the pathobiological milieu, or by the polymorphisms of the genes encoding the target molecules. In this article the complex heterogeneity of the inflammatory genes regulating key molecules, which are targets of the therapeutic intervention with specific monoclonal antibodies is reviewed, along with the crucial data that could be obtained also on the inflammatory process by the ongoing clinical trials in which pharmacogenetics is mandatory.
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