Clonally restricted anti‐igg antibodies in rheumatoid arthritis

Abstract

Clonally restricted anti-IgG antibodies were detected, by isoelectric focusing (IEF) and chromatofocusing techniques, in the sera of patients with rheumatoid arthritis (RA). Anti-Fab antibodies were predominantly acidic proteins with isoelectric points of 4.5-6.5 and displayed restricted spectrotype patterns. Proteins reactive with the Fc portion of IgG showed polyclonal spectrotype patterns with alkaline PI of 7.5-9.0. A limited array of anti-Fab spectrotypes was consistently detected in RA sera when analyzed by IEF on 6M urea gels. Additional anti-Fab antibody bands were detected when the RA sera were dialyzed against 4-6M urea prior to IEF analysis, indicating that some anti-Fab antibodies exist in a complexed form in serum. Under these dissociating conditions, anti-Fab antibodies could also be detected in normal subjects, but the spectrotype patterns were more restricted than those in RA sera. Because anti-Fab antibodies may regulate normal immune responses, the increased quantity of clonally restricted ,anti-Fab antibodies in RA may indicate an abnormality of this immunoregulation.~~p -

Anti-Fab antibodies in humans. Predominance of minor immunoglobulin G subclasses in rheumatoid arthritis.

“…1 b). These proteins, which we have previously identified as immunoglobulins (16), were most prominent in the acidic region of the gel, although diffuse uptake was often noted in the alkaline region. A comparison of the total protein pattern with the autoradiographs indicated that a high proportion of the proteins in the acidic region of the gel had anti-Fab properties (Fig.…”

“…Furthermore, treatment of sera with urea before analysis was obligatory for detection of the IgG4 subclass of antibodies, either by ELISA or by IEF (16 (14) have demonstrated that aFABA circulate with antikeyhole limpet hemocyanin antibodies after immunization of humans with keyhole limpet hemocyanin. Their studies might explain our finding higher IgG4 antidiphtheria antibody levels in untreated sera compared to those found in matched samples dialyzed against urea.…”

“…We have recently demonstrated that a portion of aFABA in RA and in some normal individuals are a unique group of immunoglobulins which are clonally restricted and have acidic isoelectric points (16). These aFABA require dissociating conditions with urea for their optimal detection by isoelectric focusing (IEF) analysis, confirming their existence in serum as complexes, and are generally in higher quantity in RA sera.…”

Human IgG anti-F(ab′)2 antibodies possess rheumatoid factor activity

“…These antibodies, particularly IgG RF, have been implicated in the pathogenesis of RA (Winchester, Agnello & Kunkel, 1970). However, a second group of anti-IgG antibodies, specific for Fab molecules, are also prevalent in RA (Persselin, Louie & Stevens, 1984;Persselin & Stevens, 1985; Abdou, 1985) and may also contribute to the disease process in these patients.…”

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

“…Since the RFs produced in adult RA are polyclonal in nature, although of restricted heterogeneity (17), most structural and serologic studies on RFs have taken advantage ofthe syndrome of mixed cryoglobulinemia. Extensive studies of these human monoclonal RFs have defined groups of RFs based on the expression of cross-reactive idiotypes (18,19).…”