F.63. Phenotype-Genotype Analysis of Familial and Sporadic Blau Syndrome: Results from An International Registry

Abstracts that activation of innate immune receptors may be important in the induction of IFN-I and the pathogenesis of SLE, we examined the activation of splenocytes from knockout mice by various innate immune receptor ligands. Data will be presented that demonstrate specific defects in proliferation and cytokine production in response to these ligands in knockout animals. Importantly, mice deficient for IFN-I signaling components failed to develop proteinuria, indicating that this pathway may play a pathogenic role in end-organ kidney damage. Therefore, this study further indicates a role for the IFN system in the pathogenesis of SLE. doi:10.1016/j.clim.2006.04.102

F.63. Phenotype-Genotype Analysis of Familial and Sporadic Blau Syndrome: Results from An International Registry. Tammy Martin,1 Trudy Doyle,1 Jinnell Lewis,1 Carine Wouters,3 Carlos Rose.2 1Ophthalmology, Oregon Health & Science Univ., Portland, OR; 2Rheumatology, Thomas Jefferson University, Philadelphia, PA; 3 Rheumatology, Gasthuisberg University Hospital, Leuven, Belgium. Familial juvenile systemic granulomatosis (Blau syndrome) is a rare disease characterized by granulomatous arthritis, dermatitis and uveitis. However, isolated reports suggest the spectrum of disease is wider involving systemic granulomatous inflammation and large vessel vasculitis. The disease is autosomal dominant with mutations in CARD15. Early onset sarcoidosis (EOS) represents a sporadic form of this disorder based on documented de novo CARD15 mutations. In an effort to improve the clinical definition and genetic understanding of the disease, an International Registry was established in 2004. Inclusion criteria required presence of arthritis and demonstration of granuloma in either synovium, skin or visceral tissues. A total of 24 index cases were identified (12 from Europe, 10 North America, and 2 South America). Seven were familial and 17 were sporadic cases. Based on clinical data, 7 cases exhibited atypical disease, such as bone involvement, panniculitis or widespread granulomatosis. Among the 24 index cases, the average age of onset was 29.6 months (range 1-132 months). Arthritis was documented in 22, uveitis in 18, and dermatitis in 19 index cases. Other disease manifestations included 5 with disseminated disease, 3 liver granuloma, and 4 erythema nodosum. CARD15 genotyping was performed for 16/24 index cases and their available family members (47 individuals total). CARD15 mutations encoding amino acid 334 substitution (R334Q or R334W) was observed in 10 index cases and their affected family members. No disease-associated CARD15 mutations were observed in the remaining 6 cases tested. There was a remarkable correlation between CARD15 mutation and the ‘‘classical’’ manifestations of Blau syndrome. This International Registry represents the largest cohort of Blau syndrome/EOS cases to be carefully phenotyped and genotyped for CARD15 mutations. doi:10.1016/j.clim.2006.04.103

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F.64. T-Cells Derived from Patients with Systemic Lupus Erythematosus Exhibit a Reversible Defect in the Mechanisms of Anergy Induction. Maria Ines Vargas Rojas, Jose Crispin, Gabriel Carrasco, Jorge Alcocer Varela. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. Defects in tolerance mechanisms that lead to the production of autoantibodies against intranuclear antigens are present in most patients with systemic lupus erythematosus (SLE). T-cell help is required for the generation of such autoantibodies. Further, the process of anergy induction has been reported to be impaired in SLE-derived Tcells. However, although such defect is probably involved in the pathogenesis of the disease, it is poorly understood. In this study, we analyzed the mechanisms of anergy induction in T-cells derived from SLE patients. 15 patients with SLE and 15 healthy subjects participated. CD4+ T-cells were isolated and expression of cell activation markers and costimulatory molecules was measured with flow cytometry in basal conditions and after stimulation with productive and anergy-inducing stimuli. Cell proliferation and cytokine production were also quantified in the mentioned settings. Anergy was induced by incubation with anti-CD3 or ionomycin, and was defined as an absence of proliferation and IL-2 secretion after a productive stimulus (anti-CD3 plus anti-CD28). Kinetics and levels of expression of costimulatory molecules were normal in T-cells from SLE patients. Tcells from SLE patients were resistant to anergy induction after incubation with anti-CD3. The defect was also present when cells were incubated with ionomycin. There was no difference in the anergy induction process between cells derived from active and inactive patients. The capacity to undergo anergy restored completely in T-cells from SLE patients after 48 hours of rest in stimuli-free medium. CONCLUSION. T-cells from patients with SLE have an impaired capacity to become anergic; such defect probably depends on factors external to the T-cell and not to an intrinsic T-cell abnormality. doi:10.1016/j.clim.2006.04.104

F.65. Effect of Modified Proteins in the Inflammation in Joint Tissue from Rheumatoid Arthritis (RA) Or Osteoarthritis (OA) Patients. Janette Furuzawa-Carballeda,1 Olga Munoz-Chable,1 Jorge Alcocer-Varela,1 Efrain Diaz-Borjon,2 Jorge Barrios-Sierra,3 Rogelio Hernandez-Pando.3 1 Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; 2Orthopedy, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; 3 Experimental Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. In the study was evaluated the antiinflammatory effect of modified extracellular matrix proteins (MECMP) in cartilage and synovial tissue co-cultures from 6 patients