Lab Research Focus
The primary interests of our laboratory relate to the pathogenesis of autoimmune disease, particularly the mechanisms underlying autoantibody expression. Considerable evidence indicates that autoantibodies such as rheumatoid factors (RF) participate in the pathogenesis of diseases such as rheumatoid arthritis (RA). In previous studies we, and others, have made progress in defining the structural diversity of RF paraproteins and RF expressed in RA. Although several germlike Vk genes are capable of encoding RF specificities, two (Humkv 328 and Humkv 325) predominate among RF paraproteins. Our recent studies indicate that these two genes are also prominently expressed in RA and that patterns of somatic mutation exhibited by transcripts derived from these genes strongly suggest an antigen-driven mechanism of expression. Two monocional antibodies (17.109 and 6B6.6) recognize germline Humkv 325 and Humkv 328 products, respectively. In previous studies we demonstrated that these two anti-ids recognize ~ 2/3 of all IgMk RF paraproteins but only an exceedingly small fraction (-1%) of RF present in RA. We have hypothesized that this discrepancy is at least partially explained by the presence of considerable somatic mutation in the Humkv 328- and Humkv 325-derived k light chains in RA. Current efforts are directed toward mapping the 6B6.6 and 17-109 idiotopes to verify this hypothesis.
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