IMMUNOPRINTING EXCLUDES MANY POTENTIAL SUSCEPTIBILITY GENES AS PREDISPOSING TO EARLY-ONSET PAUCIARTICULAR JUVENILE CHRONIC ARTHRITIS EXCEPTHLA CLASS-II AND TNF

DNA profiles (immunoprints) were generated for 120 patients suffering from early onset pauciarticular chronic arthritis (EOPA-JCA) and >500 healthy controls utilizing highly polymorphic microsatellites in the v icinity of immunorelevant genes. Six T cell receptor (TCR) markers for the CD3D, TCRDVAJ, TEA, TCRBV6S1, BV6S3, BV6S7 and BV13S2 genes were analysed. Furthermore markers for the cell surface molecule CD40L, for cytokine genes (IL-1A, IL-2, IFN-alpha, FGF-alpha, TNF-alpha), the ch romosomal region of the IRF2 and the cytokine receptor gene IL5RA were studied as well as two polymorphisms within the promotor region of th e TNF-alpha gene. Coding region polymorphisms were evidenced indirectl y by repeat length variation or they were predicted from the microsate llite distribution profiles and then confirmed by direct sequence anal ysis. Statistical evaluations were performed with respect to known pre dispositions, predominance of females (>80%) and HLA-DR and -DQ haplot ypes. Cell surface molecules (TCR, CD40L, IL5RA) as well as almost all cytokines (IL-1A, IFN alpha, FGFA, IRF2 region) were excluded as pred isposing in our JCA panel. The TNF-alpha microsatellite alleles (GT)(1 0-12) contribute considerably to manifestation of the disease, in HLA- DRB111(12) individuals (RR = 12.8). The TNF-alpha allele is not found in linkage disequilibrium with HLA-DRB111(12) and may be present on either chromosome 6. Thus, a novel susceptibility factor probably with in the TNFA/TNFB gene region has been identified via linkage with the TNF-alpha microsatellite allele. Apparently complex compositions of th e genetic background rather than single genes provide the precondition for manifestation of the autoimmune disease EOPA-JCA. Immunoprinting unravels the variability of the immunological genome via the semi-dire cted microsatellite approach efficiently.