Open AccessA systematic approach to defining the germline gene counterparts of a mutated autoantibody from a patient with rheumatoid arthritis
Author(s) -
SotoGil Rafael W.,
Olee Tsaiwei,
Klink Brenda K.,
Kenny Thomas P.,
Robbins Dick L.,
Carson Dennis A.,
Chen Pojen P.
Publication year - 1992
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780350316
Subject(s) - germline , autoantibody , germline mutation , rheumatoid factor , rheumatoid arthritis , gene , somatic cell , genetics , mutation , biology , immunology , medicine , antibody
Objective. To define the germline counterparts of potentially highly mutated autoantibodies in disease states. Methods. We developed a systematic approach by first characterizing a rearranged Ig gene and its upstream flank, and then designing suitable primers to amplify specifically the putative germline counterpart. Results. We identified and characterized the germline counterpart of a rheumatoid factor heavy chain variable region. Conclusion. We showed unequivocally that the heavy chain of a rheumatoid factor, derived from synovial tissue, has 4 replacement mutations from the corresponding germline gene. The technique allows quick assessment of the degree of somatic mutation in many autoantibodies, and thus can help to elucidate the underlying mechanisms for the induction and sustained production of such antibodies in patients.