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ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and progressive destruction of the joint cartilage and underlying bone, together with diverse extra-articular manifestations. Cytokines act as soluble effector mediators of the inflammatory process. Therapeutic neutralization with monoclonal antibodies against the pro-inflammatory cytokines TNF-alpha and interleukin 1 (IL-1) has shown a clear efficacy on inflammation and clinical manifestations of RA, although a percentage of patients do not respond. This review covers new relevant cytokines in the RA physiopathology and potential biomarkers of inflammation. The current challenge is to develop biomarkers that enable an earlier diagnosis, as well as prognostic markers and new therapeutic candidates. Combined administration of several of these cytokines could eventually address a personalized treatment approach for each patient.
Reumatologia clinica. 03/2011; 6S3:S20-4.
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ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints and several extra-articular manifestations that account for increased morbimortality of these patients. The involvement of B cells in RA pathophysiology was recognized early, with the discovery of rheumatoid factor antibody. Recently, a number of autoantibodies against citrullinated proteins have been described, of which anti-cyclic citrullinated peptide (anti-CCP) is the most specific for RA. A cohort of 937 patients with RA was studied to determine the clinical correlates of anti-CCP antibodies. The presence of anti-CCP antibodies correlated with worse joint involvement and several extra-articular manifestations, i.e., higher incidence of ischemic heart disease independent of classic cardiovascular factors and higher mortality rate. A multivariate logistic regression model showed that only anti-CCP antibodies were independently associated with the development of ischemic heart disease in patients with RA. The clinical value of anti-citrullinated protein antibodies and the relevance of anti-CCP antibodies in daily clinical practice are reviewed.
Drug News & Perspectives 11/2009; 22(9):543-8. · 2.21 Impact Factor
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Francisco Javier López-Longo,
Desamparados Oliver-Miñarro,
Inmaculada de la Torre,
Eugenia González-Díaz de Rábago,
Silvia Sánchez-Ramón,
Margarita Rodríguez-Mahou,
Alexandra Paravisini,
Indalecio Monteagudo,
Carlos-Manuel González,
Marta García-Castro,
María Dolores Casas,
Luis Carreño
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ABSTRACT: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA.
Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events.
We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17-5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01-2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19-6.56; P = 0.009).
Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.
Arthritis & Rheumatism 05/2009; 61(4):419-24. · 7.87 Impact Factor
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Francisco Javier López Longo
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ABSTRACT: Myopathies are diseases characterized by the primary affection of skeletal muscle. In general they present with muscle weakness, pain, contracture, paresthesias, rigidity, or fatigue. They can be hereditary, such as muscle dystrophies, congenital, myotonic, metabolic, and myasthenic, or acquired. Among the latter ones we include idiopathic inflammatory myopathies (IIM), toxic, endocrine, or infectious myopathies and myasthenia gravis. There is a current acceptance of considerable clinical and histopathological overlap among some muscle dystrophies and some IIM. However, the molecular profile is different and characteristic in each myopathy and the study into the patterns of expression of genes in the muscle can be useful in their differential diagnosis, including that of IIM.
Reumatología Clínica 03/2008; 4S1:40-4.
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Medicina Clínica 08/2007; 129(7):255-7. · 1.38 Impact Factor
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Arthritis & Rheumatism 09/2006; 55(4):657-61. · 7.87 Impact Factor
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ABSTRACT: . To compare the diagnostic value of anti-cyclic citrullinated peptide (anti-CCP) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis (RA) in an outpatient clinic for connective tissue diseases and spondyloarthritides.
A cross-sectional study was carried out to analyze the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250 randomly selected patients. The disease distribution in the study was as follows: 87 patients had RA (34.8%); 90 (36%) had other connective tissue diseases (CTD); 50 (20%) spondyloarthritis; 19 (7.6%) polymyalgia rheumatica; and 4 (1.6%) juvenile idiopathic arthritis.
Anti-CCP antibodies were detected in 63 patients with RA and in 9 patients with other illnesses [sensitivity 72.4%, specificity 94.4%, positive predictive value (PPV) 87.5%]. Anti-Sa antibodies were detected in 38 patients with RA and in 6 patients with other illnesses (sensitivity 43.6%, specificity 96.3%, PPV 86.3%). Anti-CCP and anti-Sa results were discordant in up to 47 of 87 RA patients. No relation between the presence of anti-Sa and higher or lower titers of anti-CCP antibodies was observed.
The diagnostic value in RA is similar for both antibodies. However, the sensitivity of anti-CCP detection is higher than that of anti-Sa. Our results suggest that presence of anti-Sa antibodies in serum may be useful as a complementary assay when anti-CCP antibodies are negative and RA is suspected.
The Journal of Rheumatology 09/2006; 33(8):1476-81. · 3.69 Impact Factor
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ABSTRACT: Anti-Sa antibodies have been described to be a highly specific marker for rheumatoid arthritis (RA). We demonstrate the existence of 2 different subsets of anti-Sa antibodies, only one of which is specific for RA. Our objective was to purify the Sa antigen, and to achieve partial characterization of these proteins.
Saline extract and mitochondrial extract from human placenta were used as antigenic sources. Antigens were purified by immunoaffinity chromatography and studied by ELISA and immunoblotting.
Three antigenically active bands of 68, 50, and 46 kDa were purified from the saline extract by immunoaffinity chromatography. Two other bands of 29 and 10 kDa that do not react with anti-Sa antibodies were obtained as well. The 68 kDa band was purified from a mitochondrial extract. These bands are not the same as other known mitochondrial autoantigens such as M2, M4, or M9. The amino terminal sequence of the 68 kDa Sa band is DEPKXEVP. The sequence of the 68 kDa Sa band is not compiled in the databases we searched, as either aminoterminal or internal sequence. Antibodies to 50/46 kDa anti-Sa bands detected by immunoblotting were highly specific for RA, while the 68 kDa antigen reacted in ELISA with sera from patients with RA and systemic lupus erythematosus, the latter showing a marked increase in features of RA. Antibodies directed against the 68 and 50/46 kDa Sa bands fluctuated with time, the 50/46 kDa anti-Sa antibodies present during the active period of the disease, and the 68 kDa anti-Sa antibodies during the remission period.
At least 2 subsets of autoantibodies are present in anti-Sa sera, one directed against a 68 kDa Sa protein and another to the typical 50/46 bands of the Sa system.
The Journal of Rheumatology 11/2002; 29(10):2053-60. · 3.69 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of activated helper T-cells that induce a B-cell response, resulting in the secretion of pathogenic autoantibodies and the formation of immune complexes. SLE in children is a disease of low prevalence with a wide range of clinical manifestations, which means that the number of randomized controlled studies are few and usually involve a small number of patients. In recent years, new therapeutic agents have appeared and the role of older treatments has been clarified. Many of these treatments are designed to reduce inflammation. The spectrum is broad and ranges from traditional nonsteroidal anti-inflammatory drugs (NSAIDs) to cytotoxic agents that have anti-inflammatory effects. The current treatment of children or adults depends on the clinical expression of the disease. Minor manifestations usually respond to the administration of NSAIDs, low doses of corticosteroids, hydroxychloroquine, or methotrexate. Thalidomide could be used for refractory skin lesions. Major manifestations can endanger the patient's life and require early, aggressive treatment. Kidney disease and other manifestations have been related to the formation or deposit of tissular immune complexes. Therefore, for years the main aim of treatment has been to suppress the immune response. The immunosuppressant treatments used in children with SLE include high doses of corticosteroids, azathioprine, methotrexate, cyclosporine, and cyclophosphamide. Several combinations of medications have been used to obtain a rapid remission or to reduce the risk of toxicity of prolonged administration of cytotoxic agents. Intravenous gamma-globulin has been successfully used in the treatment of lupus nephritis, vasculitis, and acute thrombocytopenia. In spite of numerous published studies, the use of these drugs is still controversial. The immunosuppression achieved with these treatments is nonspecific, not always effective, and associated with significant toxicities; the most significant being growth retardation, accelerated atherosclerosis and severe infectious complications. The purpose of new biological therapies is to achieve specific immunosuppression, which makes it possible to design more effective and less toxic therapeutic strategies. Mycophenolate mofetil is a promising alternative in patients who do not respond to high doses of cyclophosphamide or azathioprine. Some recently developed monoclonal antibodies such as anti-CD40L or anti-IL-10, or other molecules such as LJP394 may prove useful in the near future. Finally, stem cell transplantation may be proposed in patients with severe juvenile-onset SLE who do not respond to any treatment.
Paediatric Drugs 02/2002; 4(4):241-56. · 1.79 Impact Factor
