Rheumatoid Arthritis: Cabral AR

Furuzawa-Carballeda J, Cabral AR, Zapata-Zuñiga M, Alcocer-Varela J. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. · J Rheumatol. · Pubmed #12563677 No free full text.

Abstract: OBJECTIVE: To determine the efficacy, tolerance and safety of subcutaneous injections of porcine type I collagen-polyvinylpyrrolidone (PVP) in patients with rheumatoid arthritis (RA). METHODS: Eleven patients with active RA on stable therapy with methotrexate (MTX) were enrolled in a 3 month prospective and longitudinal study. Patients were treated weekly with subcutaneous injections of 0.2 ml of collagen-PVP (1.7 mg of collagen) in the 8 most painful joints. The primary endpoints included the Ritchie index (RI), swollen joint count, disease activity score (DAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The secondary endpoints included morning stiffness, pain intensity on a visual analog scale (VAS), and the Spanish-Health Assessment Questionnaire Disability Index (HAQ-DI). Improvement was determined using American College of Rheumatology (ACR) response criteria. RESULTS: Collagen-PVP was safe and well-tolerated and there were no adverse events. Patients had a statistically significant improvement (p < 0.05) in basal versus 3 month's treatment in morning stiffness (Delta -32.3, -68.6%), RI (Delta -10.2, -46.4%), swollen joint count (Delta -10.7, -71.8%), VAS (Delta -39.9, -63.8%), HAQ-DI (Delta -0.5, -48.5%), DAS (Delta -1.35, -70.5%) and ACR20, 50, and 70 (80.0%; 60.0% and 20.0% respectively). We found no differences in serologic or hematologic variables. CONCLUSION: Collagen-PVP was a safe and well-tolerated drug for the short term treatment of RA. The combination of collagen-PVP plus MTX was more efficacious than MTX alone. However, double-blind placebo-controlled phase II and III clinical trials are necessary to determine whether this drug could be useful in the longterm treatment of RA.

Furuzawa-Carballeda J, Macip-Rodríguez PM, Cabral AR. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico. · Clin Exp Rheumatol. · Pubmed #18799084 No free full text.

Abstract: OBJECTIVE: Pannus in osteoarthritis (OA) has only recently been characterized. Little is known, however, regarding the behavior of OA pannus in vitro compared to rheumatoid arthritis (RA) pannus. The purpose of our study was to compare OA with RA pannus. METHODS: Pannus and synovial tissue co-cultures from 5 patients with OA and 5 patients with RA obtained during arthroplasty were studied. Pannus was defined as the microscopic invasive granulation tissue covering the articular surface. Tissues were cultured for 7 days and stained with Alcian Blue technique. Interleukin-1beta (IL-1beta), IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were also determined in supernatants by ELISA. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were also detected by immunohistochemistry. RESULTS: All patients had vascular or fibrous pannus. Synovial proliferation, inflammatory infiltrates and a decrease of extracellular matrix proteins were observed in all tissue samples. Chondrocyte proliferation was lower in OA than RA cartilage. OA synovial tissue expressed lower levels of proteoglycans than RA synoyium. Type II collagen levels were lower in OA than in RA cartilage. Significantly higher levels of IL-1beta were found in the supernatants of RA pannus compared to OA pannus (p<0.05). High but similar levels of TNF-alpha, IL-8 and TIMP-1 were detected in OA and RA pannus supernatants. IL-10, IL-12 and IFN-gamma were undetectable. CONCLUSION: RA and OA pannus had similar pro-inflammatory and anti-inflammatory cytokine profile expression. OA cartilage, synovial tissue and pannus had lower production of proteoglycans, type II collagen and IL-1beta. It remains to be elucidated why OA pannus invades the cartilage surface but does not cause the marginal erosions typically seen in RA.

Damián-Abrego GN, Cabiedes J, Cabral AR. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. · Lupus. · Pubmed #18413411 No free full text.

Abstract: The objective was to study the association of antibodies against cyclic citrullinated peptides (anti-CCP) in patients with lupus articular damage. We studied 34 systemic lupus erythematosus patients (30 women) with (n = 14) or without (n = 20) deforming arthropathy. Anti-DNA and arthritis were mandatory inclusion criteria for both groups. As controls, 34 patients with rheumatoid arthritis and nine patients with rheumatoid arthritis and systemic lupus erythematosus (rhupus) were included. Anti-CCP and rheumatoid factor were determined by ELISA and nephelometry respectively. All patients had recent x-ray films of the hands that were evaluated according to Sharp's method. Systemic lupus erythematosus patients had a mean 6.50 +/- 0.86 (SD, range 5-8) American College of Rheumatology (ACR) criteria, rheumatoid arthritis patients met 5.38 +/- 0.60 (range 4-6) ACR criteria for rheumatoid arthritis and rhupus patients had 5.78 +/- 0.44 (range 5-6) criteria for rheumatoid arthritis and 5.11 +/- 0.78 (range 4-6) for systemic lupus erythematosus. Systemic lupus erythematosus patients, with or without deforming arthropathy, had normal serum anti-CCP concentrations. In contrast, rheumatoid arthritis and rhupus patients had 30- and 23-fold higher than normal amounts of anti-CCP (p < 0.001, both comparisons). Rheumatoid arthritis (97%) and rhupus (100%) patients were more frequently positive for anti-CCP than SLE patients with (7%) or without (5%) deforming arthropathy (p < 0.001, both comparisons). Patients with lupus deforming arthropathy were more frequently positive for rheumatoid factor (65%) than patients with non-deforming arthritis (15%) (p = 0.005). Patients with lupus deforming arthropathy had similar frequency of erosions and mean Sharp's score than rhupus patients. Anti-CCP antibodies do not associate with lupus arthropathy, whether deforming, non-deforming or erosive.

Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral AR. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15 Tlalpan, Mexico City 14000, Mexico. · Autoimmun Rev. · Pubmed #17289553 No free full text.

Abstract: Recent studies demonstrated an IL-17-producer CD4+ T cell subpopulation, termed Th17, distinct from Th1 and Th2. It represents a different pro-inflammatory Th-cell lineage. This notion is supported by gene-targeted mice studies. Mice lacking IL-23 (p19-/-) do not develop experimental autoimmune encephalomyelitis (EAE) or collagen-induced arthritis (CIA), while knockout mice for the Th1 cytokine IL-12 (p35-/-) strongly develop both autoimmune diseases. Disease resistance by IL-23 knockout mice correlates well with the absence of IL-17-producing CD4(+) T lymphocytes in target organs despite normal presence of antigen-specific-IFN-gamma-producing Th1 cells. This finding may thus explain previous contradictory reports showing that anti-IFN-gamma-treated mice, IFN-gamma- or IFNR-deficient mice develop CIA or EAE. TGF-beta, IL-6 and IL-1 are the differentiation factors of Th17 cells. IL-23 is dispensable for this function, but necessary for Th17 expansion and survival. The master regulator that directs the differentiation program of Th17 cells is the orphan nuclear receptor RORgammat. IL-27, a member of the IL-12/IL-23 family, potently inhibits Th17 development. Evidence suggesting rheumatoid arthritis and multiple sclerosis as primarily IL-17 autoimmune inflammatory-mediated diseases is rapidly accumulating. The IL-17/23 axis of inflammation and related molecules may rise as therapeutic targets for treating these and perhaps other autoimmune diseases.