COMPARISON OF RHEUMATOID FACTORS OF RHEUMATOID-ARTHRITIS PATIENTS, OFINDIVIDUALS WITH MYCOBACTERIAL INFECTIONS AND OF NORMAL CONTROLS - EVIDENCE FOR MATURATION IN THE ABSENCE OF AN AUTOIMMUNE-RESPONSE
N. Djavad et al., COMPARISON OF RHEUMATOID FACTORS OF RHEUMATOID-ARTHRITIS PATIENTS, OFINDIVIDUALS WITH MYCOBACTERIAL INFECTIONS AND OF NORMAL CONTROLS - EVIDENCE FOR MATURATION IN THE ABSENCE OF AN AUTOIMMUNE-RESPONSE, European Journal of Immunology, 26(10), 1996, pp. 2480-2486
We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus
-transformed monoclonal B cells established from four patients with rh
eumatoid arthritis (RA), three individuals with a history of Mycobacte
rium tuberculosis (TB) and four normal controls (NI), Fifty-eight RF w
ere analyzed for specific activity (international units-RF/mu g) for t
he Fe part of IgG and their interaction with tetanus toxoid (TT) and D
NA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain
region of IG (9TB-/7RA-) RE Significant differences were observed betw
een tile NT-RF and the TB- and RA-RE While the RF repertoire of normal
individuals comprised of low-avidity RF of which the majority (15/17)
were polyspecific, more than half of the TB- and RA-RF were monoreact
ive. Furthermore, the monospecific TB- and RA-RF were of signifi cantl
y higher avidity than the NI-RF (RA > TB much greater than NI), With r
espect to polyspecificity, the RF in the three groups were comparable:
the interaction with DNA, TT as well as with Fc was inhibited either
by an increase of the ionic strength to 0.3-0.5 M NaCl or by addition
of the polyanion dextran sulfate, indicating that the antibodies inter
acted with similar anionic epitopes shared by the three antigens. Anal
ysis of the V-D-J heavy chain regions showed significant diferenccs be
tween the respective RF. The salt-sensitive binding was highly correla
ted with the presence of arginine in the complementarity-determining r
egion 3 (CDR3). Furthermore, whereas the polyspecific RF consisted pre
dominantly of germ-line encoded antibodies, the genes of the monospeci
fic RA/TB-RF were somatically mutated (RA > TB). It is therefore likel
y that maturation of RF can be initiated by chronic infections and tha
t monospecific, somatically mutated RF are not a unique characteristic
of autoimmune diseases.