Rheumatoid factor inhibition of in vitro binding of IgG complexes in the human glomerulus

Abstract

We studied the effects of rheumatoid factor (RF) on binding of immune complexes to activated C3 (C3b) receptors in vitro. IgM fraction of serum containing RF activity (IgM‐RF), IgM isolated from pooled normal human serum and having no RF activity (IgM‐control), bovine serum albumin, and Veronal buffered saline solutions were used in a C3b assay system consisting of aggregated human IgG (AggHuIgG) coupled to sheep erythrocytes (SRBC) with guinea pig and normal human serum complement. The number of glomerular bound AggHuIgG‐SRBC with IgM‐control and bovine serum albumin or Veronal buffered saline was similar, while the number of bound cells with IgM‐RF was reduced significantly. This effect was seen with both guinea pig and normal human serum complements. Supernatant hemolytic complement activity was maintained with IgM‐RF, but reduced with control solutions. The blocking factor was shown to be RF by serial dilutions of IgM‐RF resulting in inverse correlations with latex flocculation and inhibition of SRBC binding, absorption of blocking from IgM‐RF with insolubilized AggHuIgG, and failure of IgM‐control to block binding. IgM‐RF did not directly interfere with activation of complement, but blocked attachment of C3 to AggHuIgG and formation of C3b capable of reacting with glomerular receptors. These results showed that IgM‐RF can inhibit binding of AggHuIgG complexes to human glomeruli. This in vitro phenomenon may represent a possible protective mechanism of RF in vivo in diseases with immune complexes.

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

“…In another study, it was shown that IgM-RF could block attachment of C3b, which is capable of reacting with glomeruli receptors, indicating that IgM-RF can inhibit binding of immune complexes to human glomer- uli (29). This in vitro phenomenon may represent a possible protective mechanism of RF in vivo in immune complex diseases.…”

The lupus patient with positive rheumatoid factor

“…It has also been shown that RF blocks the attachment of C3 to aggregated IgG, not allowing its reaction with C3b receptors of glomeruli and thus shielding them from deposition of pathogenic immune complexes. 22…”

Origin and Age-Associated Changes in the Expression of a Physiologic Autoantibody

“…Another may be to reduce the binding of the first component of complement to IgG. Since RF may reduce the total complement binding to immune complexes, it may reduce the attachment of the complexes to C3 receptors in the renal glomerulus, thus preventing glomerulone phritis [6], Of main general biological signifi cance is the possibility that RF may clear the periphery and tissues of idiotype-anti-idiotype immune complexes [39]. The continued prevalence of RF in various autoimmune diseases and in many elderly individuals may simply imply changes in the homeostatic feedback mechanisms associated with or fol lowing the development of immunodefi ciency states that may accompany these con ditions [31],…”