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  • 1
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; HLA-DR antigens ; Conformational equivalence hypothesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P〈0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P〈0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P〈0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P〈0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Key words HLA ; interleukin-2 (IL-2) ; CTLL-20 cells ; Limiting Dilution Anaysis (LDA) ; HTLp frequencies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty nine healthy unrelated individuals were carefully selected and divided into three groups according to their HLA (Human Leukocyte Antigens) phenotypes. A sensitive and reproducible limiting dilution analysis (LDA) based bioassay using CTLL-20 cells for detection of human IL-2 was set up and used to assess the hierarchical impact of highly polymorphic HLA molecules on individual’s alloreactivity. Our main interest was to evaluate the role of HLA-DP molecules in this process. By calculating frequencies of IL-2 producing helper T cell precursors (HTLp) and amounts of IL-2 produced in each experiment, we were able to confirm that HLA-DR molecules are the most potent alloantigens. In 29 different combinations where a single HLA-DP mismatch between stimulating and responding cells was evaluated, some were reasonably tolerant, while the other ones evoked moderate to relatively strong alloimune responses. Finally, two groups with statistically significant difference in alloimune responses to stimulating HLA-DP molecules carrying D,E,A,V or G,G,P,M amino acid sequences at positions 84,85,86 and 87 in the sixth variable region F of the molecule could be formed, according to HTLp frequencies and amounts of IL-2 detected. Data presented are of great importance for the selection of unrelated as well as related bone marrow donors for haematological patients.
    Type of Medium: Electronic Resource
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