ISSN:
1744-313X
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Biologie
,
Medizin
Notizen:
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 vicinity 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-α, FGF-α, TNF-α), the chromosomal region of the 1RF2 and the cytokine receptor gene IL5RA were studied as well as two polymorphisms within the promotor region of the TNF-α gene. Coding region polymorphisms were evidenced indirectly by repeat length variation or they were predicted from the microsatellite distribution profiles and then confirmed by direct sequence analysis. Statistical evaluations were performed with respect to known predispositions, predominance of females (〈80%) and HLA-DR and -DQ haplo-types. Cell surface molecules (TCR, CD40L, IL5RA) as well as almost all cytokines (IL-1 A, IFNα, FGFA, IRF2 region) were excluded as predisposing in our JCA panel. The TNF-a microsatellite alleles (GT)10–12 contribute considerably to manifestation of the disease, in HLA-DRB1*11(12) individuals (RR = 12.8). The TNF-α allele is not found in linkage disequilibrium with HLA-DRB1*11(12) and may be present on either chromosome 6. Thus, a novel susceptibility factor probably within the TNFAITNFB gene region has been identified via linkage with the TNF-α microsatellite allele. Apparently complex compositions of the 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-directed microsatellite approach efficiently.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1744-313X.1995.tb00247.x
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