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ABSTRACT: Objectives: CD4+CD25high regulatory T cells (TREG) represent a suppressive T cell subset deeply involved in the modulation of immune responses and eventually in the prevention of autoimmunity. Growing evidence demonstrated that patients with autoimmune and inflammatory chronic diseases display an impairment of TREG cells or activated effector T cells unresponsive to TREG. Glucocorticoid-induced TNFR-related protein (GITR) is a widely accepted marker of murine TREG cells, but little is known in humans. Aim of the present study was to investigate the characteristics of different subsets of TREG cells in Sjögren's syndrome and the potential role of GITR as marker of human TREG cells. Methods: Fifteen patients with primary Sjogren's syndrome (SS) and 10 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies. Disease activity was assessed using the EULAR Sjögren's syndrome disease activity index (ESSDAI). Results: Although the proportion of circulating CD25highGITRhigh subset was similar in SS patients and NC, an expansion of the CD25-GITRhigh cell population was observed in the peripheral blood of SS patients. Interestingly, this expansion was more relevant in patients with inactive rather than active disease. Conclusions: The number of CD4+CD25-GITRhigh cells is increased in SS as compared to NC. Moreover, the fact that the expansion of this cell subset is prevalently observed in patients with inactive disease suggests that these cells may play a role in counteracting inflammatory response.
Reumatismo 01/2012; 64(5):293-8.
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N Bizzaro,
F Allegri,
C Alpini,
A Doria, R Gerli,
M Lotzniker,
A Mathieu,
G Morozzi,
F Bellisai,
V Riccieri,
M Tampoia,
P Migliorini
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ABSTRACT: A novel immunoenzymatic assay using viral citrullinated peptides derived from Epstein-Barr virus-encoded proteins (viral citrullinated peptide 2 (VCP2)) has been developed and evaluated by means of a multicentre collaborative study.
Three hundred nine sera from patients with established rheumatoid arthritis (RA), 36 with early arthritis, 12 with juvenile arthritis and 453 controls were tested for VCP2 and cyclic citrullinated peptide (CCP) antibodies.
The VCP2 assay showed 78.3% sensitivity and 97.1% specificity. VCP2 and CCP had a high concordance rate in patients with RA (88%) and controls (97%). However, 36 RA sera were positive in the CCP assay but negative on VCP2, and two RA sera reacted only on VCP2.
The new VCP2 assay is endowed with high sensitivity and specificity. VCP2-positive RA sera are mostly but not completely contained in the CCP-positive population. Studies are in progress to establish whether the VCP2 assay can detect clinically distinct subsets of patients with RA.
Journal of clinical pathology 09/2011; 64(12):1139-41. · 2.43 Impact Factor
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ABSTRACT: High levels of serum and/or plasma circulating DNA (cDNA) have been described in patients with systemic autoimmune diseases (SADs). However, the role of this molecule has not been clarified. Our aim was to evaluate plasma cDNA levels in 48 systemic lupus erythematosus (SLE) and 44 primary Sjögren's syndrome (SS) patients, as compared with healthy and rheumatoid arthritis (RA) subjects, and to analyse their correlation with disease activity, disease damage and clinical manifestations. Plasma DNA was extracted using Qiagen columns and quantified by real-time quantitative PCR. Disease activity and damage were evaluated in both diseases by analysis of clinical and laboratory findings. Our results showed that plasma cDNA levels were significantly higher in patients with SS (mean ± SE: 32.0 ± 7.3 ng/ml) and with SLE (35.0 ± 9.0 ng/ml) than in controls (5.1 ± 1.1 ng/ml) (p < 0.0001 for both). Disease activity index correlated with cDNA levels in SS (p = 0.02), but not in SLE, and SS subjects with active disease displayed significantly higher cDNA levels with respect to inactive patients (p < 0.05). No correlation was found between plasma cDNA levels and disease damage indexes in either SLE or SS. These results indicate that increased plasma cDNA levels can been demonstrated in SLE and in SS patients with respect to healthy subjects. Interestingly, although cDNA levels did not correlate with indexes of disease damage in these disorders, a significant correlation between cDNA concentrations and disease activity was observed in SS, but not in SLE, suggesting a possible role of cDNA as non-invasive marker of disease activity. The different results obtained in these SADs may be explained by distinct disease pathogenesis or the influence of immunosuppressive and corticosteroid therapy that, unlike in SS, is usually employed in SLE.
Lupus 05/2011; 20(9):928-35. · 2.34 Impact Factor
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M Pirro,
E B Bocci,
F Di Filippo,
G Schillaci,
M R Mannarino,
F Bagaglia, R Gerli,
E Mannarino,
M R Manfredelli,
A M Scarponi,
others
European Journal of Internal Medicine 01/2011; 22(4):412-7. · 2.00 Impact Factor
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ABSTRACT: Regulatory T cells (T(REG)) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine T(REG) cells, but little is known in humans. The aim of this study was to investigate the characteristics of T(REG) cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human T(REG).
Nineteen SLE patients and 15 sex- and age-matched normal controls (NC) were enrolled. CD4(+) T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR) using TaqMan probes.
The CD25(high)GITR(high) subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25⁻GITR(high) cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25⁻GITR(high) and CD25(high)GITR(high) cells, suggesting that both cell subsets have regulatory activity.
CD4(+)CD25⁻GITR(high) cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.
Reumatismo 01/2010; 62(3):195-201.
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F Salaffi,
M Carotti,
A Iagnocco,
F Luccioli,
R Ramonda,
E Sabatini,
M De Nicola,
M Maggi,
R Priori,
G Valesini, R Gerli,
L Punzi,
G M Giuseppetti,
U Salvolini,
W Grassi
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ABSTRACT: To compare ultrasonography (US) of salivary glands with contrast sialography and scintigraphy, in order to evaluate the diagnostic value of this method in primary SS (pSS).
The diagnostic value of parotid gland US was studied in 77 patients with pSS (male/female ratio 3/74; mean age 54 yrs) and in 79 with sicca symptoms but without SS. The two groups were matched for sex and age. Imaging findings of US were graded using an ultrasonographic score ranging from 0 to 16, which was obtained by the sum of the scores for each parotid and submandibular gland. The sialographic and scintigraphic patterns were classified in four different stages. The area under receiver operating characteristic curve (AUC-ROC) was employed to evaluate the screening method's performance.
Of the 77 patients with pSS, 66 had abnormal US findings. Mean US score in pSS patients was 9.0 (range from 3 to 16). Subjects without confirmed pSS had the mean US score 3.9 (range from 0 to 9) (P < 0.0001). Results of sialography showed that 59 pSS patients had abnormal findings at Stage 1 (n = 4), Stage 2 (n = 8), Stage 3 (n = 33) or Stage 4 (n = 14), and 58 patients had abnormal scintigraphic findings at Stage 1 (n = 11), Stage 2 (n = 18), Stage 3 (n = 25) or Stage 4 (n = 4). Through ROC curves US arose as the best performer (AUC = 0.863 +/- 0.030), followed by sialography (AUC = 0.804 +/- 0.035) and by salivary gland scintigraphy (AUC = 0.783 +/- 0.037). The difference between AUC-ROC curve of salivary gland US and scintigraphy was significant (P = 0.034). Setting the cut-off score >6 US resulted in the best ratio of sensitivity (75.3%) to specificity (83.5%), with a likelihood ratio of 4.58. If a threshold >8.0 was applied the test gained specificity, at the cost of a serious loss of sensitivity (sensitivity 54.5%, specificity 97.5%, likelihood ratio 21.5).
Salivary gland US is a useful method in visualizing glandular structural changes in patients suspected of having pSS and it may represent a good option as a first-line imaging tool in the diagnostics of the disease.
Rheumatology (Oxford, England) 08/2008; 47(8):1244-9. · 4.24 Impact Factor
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Annals of the rheumatic diseases 06/2008; 67(5):724-5. · 8.11 Impact Factor
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ABSTRACT: Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the proportion of lymphocytes which bore the γδ T-cell receptor for antigen was significantly higher in CSF than in autologous and heterologous blood samples. γδ T-cell values in CSF of MM patients were also significantly higher than those calculated in CSF specimens from nine children with non-inflammatory neurological disorders. Whether and how the expanded CSF γδ T-lymphocyte subset, either CD8 + or double-negative (CD4-/CD8-), contributes to the eradication of mumps virus infection from the central nervous system represents a central focus of our ongoing research.
Acta Paediatrica 01/2008; 84(11):1268 - 1270. · 2.07 Impact Factor
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ABSTRACT: Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis.
Lupus 02/2007; 16(4):259-64. · 2.34 Impact Factor
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Rheumatology 01/2007; 45(12):1580-1; author reply 1581-2. · 4.06 Impact Factor
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ABSTRACT: Riassunto La sclerosi sistemica (SSc) o sclerodermia è una ma-lattia multisistemica che può interessare sia la cute che organi interni. E' una connettivite molto com-plessa sia da un punto di vista patogenetico che cli-nico, poiché il suo spettro può allargarsi dal sempli-ce fenomeno di Raynaud, a forme localizzate di fi-brosi cutanea sino a forme clinicamente più rilevanti di SSc sostenute da processi patologici flogistici, vascolari e fibrotici. E' attualmente abbastanza chia-ra una stretta relazione tra tali condizioni così diffe-renti, e la sclerosi cutanea non è più oggi considerata come essenziale per la diagnosi di SSc. Vi sono state sostanziali modifiche di classificazione della malattia e di valutazione della sua storia natu-rale associate all'introduzione negli ultimi tempi di specifiche indagini diagnostiche e nuovi trattamenti delle complicanze d'organo della malattia. Sebbene la SSc abbia ancora una elevata mortalità legata alla malattia e siano carenti efficaci terapie sistemiche specifiche per la malattia, vi sono state, infatti, im-portanti evoluzioni nel trattamento di alcuni interes-samenti d'organo come quelli renale e polmonare. Tali progressi sono esemplificati dall'introduzione nella terapia della SSc degli inibitori dell'enzima con-vertente l'angiotensina (ACE) per la crisi renale scle-rodermica e dei trattamenti avanzati per l'ipertensio-ne arteriosa polmonare di classe III e IV. Le indagini di laboratorio, ed in particolare la rileva-zione di autoanticorpi specifici di malattia, giocano un ruolo chiave per la classificazione e l'inquadra-mento prognostico del paziente sclerodermico al-l'esordio della malattia con fondamentali riflessi per un corretto approccio clinico e terapeutico della ma-lattia. Summary Autoimmunity laboratory investigations in systemic sclerosis diagnosis and monitopring – The question of the clinician Systemic sclerosis (SSc) or scleroderma is a multisystem disease that affects the skin and internal organs. It is a very complex connective tissue disease from both a pathogenic and clinical point of view, since its spectrum spans simple Raynaud's phenomenon, localized forms of skin fibrosis and the clinically most important forms of SSc sustained by inflammatory, vascular and fibrotic pathological events. A closer relationship between these disparate conditions is now appreciated, and skin sclerosis is no longer regarded as mandatory for the diagnosis of SSc. There have been substantial changes in disease classifica-tion and appreciation of its natural history associated with the recent introduction of novel investigations and treat-ments of organ-based complications. Although SSc still has a high disease-related mortality and effective disease-specific systemic treatments are lacking, there have been major improvements, indeed, in the management of some organ-based complications, including renal and pulmonary involvement. Angiotensin-converting enzyme (ACE)-inhi-bitors for scleroderma renal crisis and advanced therapies for classes III and IV pulmonary arterial hypertension exemplify progress in the treatment of SSc. Laboratory investigations and, in particular, disease-speci-fic autoantibody detection play a key role in the classifica-tion and in the prognostic assignment of scleroderma pa-tient at disease onset with fundamental effects for a cor-rect clinical and therapeutic approach of the disease.
RIMeL / IJLaM. 01/2007; 3.
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ABSTRACT: Subjects with Down's syndrome (DS), or trisomy 21, have an increased susceptibility to infections, malignant diseases and autoimmune phenomena. Various arms of the immune system are severely impaired in trisomie patients. We found that the proportion of blood lymphocytes bearing the /δ T-cell receptor (TCR) was significantly higher in adults with trisomy 21 than in age- and sex-matched healthy controls. Interestingly, the increase was mainly due to an over-expansion of cells which bear non-covalently bound /δ chains on their surface. This contrasts with the normal blood picture, where the great majority of /δ T cells express the disulphide-linked form of the TCR. The fact that trisomie /δ T cells are both numerically and phenotypically unbalanced provides further evidence that immunological abnormalities are integral features of DS.
Scandinavian Journal of Immunology 06/2006; 35(3):275 - 278. · 2.23 Impact Factor
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ABSTRACT: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA).
We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay.
The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients.
The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.
Clinical and Developmental Immunology 09/2005; 12(3):197-202. · 1.84 Impact Factor
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ABSTRACT: To evaluate the contribution of the MHC class I chain-related A (MICA) gene polymorphism to the genetic risk of systemic lupus erythematosus (SLE).
HLA-DRB1-DQA1-DQB1 genotyping, MICA exon 5 microsatellite genotyping and HLA-B8 genotyping were performed in 48 Italian SLE patients and in 158 healthy control subjects.
Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P < 0.0026]. HLA-B8 was detected in 31% SLE patients and 13% healthy control subjects (OR = 3.0, P = 0.005). The allele-wise comparison between patients and controls showed that both MICA5 (OR = 2.5, corrected P < 0.0005) and MICA5.1 (OR = 2.4, corrected P < 0.0005) were positively and MICA9 (OR = 0.2, corrected P < 0.0005) was negatively associated with the disease. The MICA5/5.1 genotype was positively associated with SLE (OR = 28.9, corrected P < 0.0015) also in subjects negative for DR3-DQ2 (OR > 22.6, corrected P < 0.011). The simultaneous presence of DR3-DQ2 and MICA5.1 was detected in 15/48 (31%) SLE and in 10/158 (6%) healthy control subjects (OR = 6.7, corrected P < 0.011). The simultaneous combination of DR3-DQ2 and MICA5 was found in 10/48 (21%) SLE patients and in only 1/158 healthy control subjects (OR = 41.3, corrected P < 0.011). Logistic regression analysis showed the independent positive associations of MICA5 and MICA5.1 and negative association of MICA9 with the disease, and revealed that the interaction of the three major markers (DR3-DQ2, MICA5 and MICA5.1) was associated with increasing genetic risk, which was highest (OR > 30.3) in DR3-DQ2-positive subjects carrying the MICA5-5.1 genotype.
Our study provides the first demonstration of the independent association of the MICA gene polymorphism with genetic risk of SLE.
Rheumatology 03/2005; 44(3):287-92. · 4.06 Impact Factor
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ABSTRACT: Cardiovascular (CV) disease morbidity and mortality are increased in patients with rheumatoid arthritis (RA) and much of the excess CV disease morbidity appears to be due to atherosclerosis. The pathogenesis of atherosclerosis (ATS) in RA is complex and there is increasing evidence that many factors including novel and traditional cardiovascular risk factors, RA treatments and the RA inflammatory disease process are involved in the development of CV disease in these patients. Of particular interest are the effects of chronic inflammation and immune dysregulation associated with RA. These have been shown to be associated with endothelial dysfunction, which is an early, potentially reversible, functional abnormality of the arterial wall. However, as several CV disease risk factors and drug prescribing are also influenced by RA disease severity it is very difficult to separate out the effects of the inflammatory disease burden on the cardiovascular system in RA.
Lupus 02/2005; 14(9):679-82. · 2.34 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis.
To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors.
Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age </=59 years), with DAS28 </=3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls.
Mean (SD) FMV was significantly lower in patients than in controls (3.2 (1.3)% v 5.7 (2.0)%; p<0.001), inversely related to low density lipoprotein cholesterol (r = -0.45, p<0.05) and C reactive protein (CRP), expressed as the value at the moment of ultrasound evaluation (r = -0.44, p<0.05), as the average of CRP levels evaluated at different times during the disease (r = -0.47, p<0.05), or as the average of >/=4 determinations multiplied by the disease duration (r = -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta = -0.28, p<0.05).
Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.
Annals of the Rheumatic Diseases 02/2004; 63(1):31-5. · 8.73 Impact Factor
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R Priori,
E Medda,
F Conti,
E A M Cassara,
M G Danieli, R Gerli,
R Giacomelli,
F Franceschini,
A Manfredi,
M Pietrogrande,
M A Stazi,
G Valesini
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ABSTRACT: The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases. The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR = 4.1; two or more, OR = 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR = 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).
Lupus 02/2003; 12(10):735-40. · 2.34 Impact Factor
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Rheumatology 01/2003; 41(12):1341-5. · 4.06 Impact Factor
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R Gerli,
L Caponi,
A Tincani,
R Scorza,
M G Sabbadini,
M G Danieli,
V De Angelis,
M Cesarotti,
M Piccirilli,
R Quartesan, [......],
I Cavazzana,
L Origgi,
M Vanoli,
E Bozzolo,
L Ferrario,
A Padovani,
O Gambini,
L Vanzulli,
D Croce,
S Bombardieri
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ABSTRACT: To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE).
Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions.
Serum anti-P were detected in 18/149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment.
This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.
Rheumatology 01/2003; 41(12):1357-66. · 4.06 Impact Factor
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ABSTRACT: T-cell cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by the complex network present in the synovium. Although many synovial T cells show signs of previous activation, only a few express interleukin (IL)-2 receptor, marker of recent activation. The aim of this study was to analyse the cytokine production by in vivo activated (IL-2R +) T cells from RA at different stages of the disease. For this purpose, T cells were isolated from peripheral blood and synovial fluid of four patients with active RA, two at the onset of the disease, one in the early phase during treatment, one in long-lasting chronic phase. One patient was studied at the onset of the disease and 52 months later. Cells were initially expanded with a low dose of IL-2, cloned and analysed for cytokine production. The results showed a strong predominance of T helper (Th) 1 clones in the blood and a slight prevalence of Th0 clones in the joint of all the four patients. Interferon-gamma and IL-2 production was higher in the long-lasting RA, whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing clones was present only in the joint of the untreated patients. The longitudinal study confirmed the differences in cytokine production between early and late phases of disease. These data confirm that RA is mainly a Th1-driven condition. However, in vivo activated synovial T cells produce also Th2-type anti-inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines is a feature of the very early phase of RA, although the selective recruitment of IL-10-producing T cells is quickly lost.
Clinical & Experimental Immunology 10/2002; 129(3):549-55. · 3.36 Impact Factor
