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1992 ; 149
(5
): 1817-24
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid
factors react with epitopes induced in Gm(a-), Gm(g-) IgG by interaction with
antigen or by nonspecific aggregation A possible mechanism for the in vivo
generation of rheumatoid factors
#MMPMID1380541
Williams RC Jr
; Malone CC
; Casali P
J Immunol
1992[Sep]; 149
(5
): 1817-24
PMID1380541
show ga
Heteroclitic rheumatoid factors (RF) are specific for allotypic determinants,
e.g., Gm(a) or Gm(g) on allogeneic, but not autologous IgG. All polyclonal RF we
isolated from nine rheumatoid arthritis patients with circulating Gm(a-), (b+),
(g-), (f+) IgG displayed dual heteroclitic activity for the Gm(a) and Gm(g)
allotypes, as shown by using appropriate RBC agglutination assays and affinity
columns bearing Gm(a+) or Gm(g+) IgG. To investigate possible mechanisms
underlying the in vivo generation of heteroclitic RF, we tested the ability of
nonspecifically and immune-specifically aggregated Gm(a-), (g-) IgG to function
as targets for RF from Gm(a-), (g-) patients with rheumatoid arthritis. Heat
aggregation (63 degrees C for 20 min) or binding to Ag (as in tetanus
toxoid-antitetanus toxoid complexes) induced a "functional" Gm(a+) and/or (g+)
phenotype in Gm(a-), (g-) IgG from five healthy subjects and five rheumatoid
patients, as suggested by the ability of these altered IgG to function as
efficient targets for six heteroclitic RF in direct binding and competitive
inhibition experiments. That heterocliticity and dual Gm(a), Gm(g) specificity
can be features of a single antibody molecule was formally demonstrated by
analysis of a monoclonal RF (IgM mAb 61) generated from a Gm(a-), (g-) rheumatoid
patient. RF mAb 61 displayed a high affinity (Kd, 10(-7) M) for IgG Fc fragment
of Gm(a+) and (g+) IgG or aggregated autologous Gm(a-), (g-) IgG but did not bind
to native autologous IgG. To investigate the molecular basis of the acquired
Gm(a) phenotype, PBMC from five Gm(a-) patients with rheumatoid arthritis and two
Gm(a-) normal subjects arthritis and two Gm(a-) normal subjects were cultured in
vitro after activation with PWM. In most instances, these PBMC produced IgG that
behaved as Gm(a+) in sensitive ELISA. Application of the polymerase chain
reaction (PCR), using probes specific for the nucleotide sequence coding for the
Gm(a) tetrapeptide, to the amplification of DNA from the in vitro-stimulated
Gm(a-) normals or rheumatoid patients' PBMC provided no evidence for Gm(a)
nucleotide sequences. The present data suggest that acquisition of the Gm(a)
determinant by Gm(a-) IgG may result from subtle changes in the CH2-CH3
RF-binding region. Such changes would occur when Gm(a) IgG are complexed with Ag
or nonspecifically altered, thereby providing a possible explanation for the
induction of heteroclitic RF in Gm(a-) rheumatoid arthritis patients.