Binding of IgM Rheumatoid Factor to Group A, C and G Streptococci with IgG Fc Receptors

Int Arch Allergy Immunol

Gharavi

Johansson

et al. 1987

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Radiolabelled monoclonal IgM rheumatoid factors, four from patients with type II essential cryoglobulinaemia and one originating from a patient with rheumatoid arthritis, were tested for binding to group A, B, C and G streptococci and Escherichia coli Two of the preparations exhibited different binding patterns for the streptococci, whereas the remaining three were not reactive. The binding of one of the factors to group A streptococci type 15 was inhibited by F(ab′)₂-fragments of anti-idiotypic antibodies but not anti-IgM Fc or F(ab′)₂ of normal rabbit IgG, indicating that the reaction was mediated via the antibody combining sites.

Section: Discussionmentioning

confidence: 99%

“…Recently, it was found that polyclonal IgM RF iso lated from patients with rheumatoid arthritis can bind to certain group A streptococci [3]. These streptococci were all shown to possess receptors for the Fc part of IgG [4][5][6] although IgG was not involved in the bind ing mechanism for IgM RF.…”

Section: Introductionmentioning

confidence: 99%

Binding of Monoclonal IgM Rheumatoid Factor to Streptococci via the Antibody Combining Site

Int Arch Allergy Immunol

Gharavi

Johansson

et al. 1987

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“…This reaction was excrted via the antibody combining sites since it was inhibited by F(ab')z fragments of anti-ld antibodies but not F(ab')2 of other antiIgM antibodies. Furthermore, we have shown the capacity ol" a fraction of two different purified polyclonal RFs fi-om patients with rheumatoid arthritis to bind to group A, C and G streptococci [47]. This binding was associated with the presence of IgG Fc receptors in the strains [47].…”

Section: Differences In the Specifities Of Human Anti-immunoglobulinsmentioning

confidence: 93%

Possible role of microbial IgG Fc-binding proteins in rheumatoid arthritis

Christensen

1990

Agents and Actions

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IgG Fc binding substances (receptors) are widespread among pathogenic microorganisms. The receptors from Staphylococcus aureus, streptococci of group A, C and G as well as Herpes-infected cells bind to the interface between the CH2 and CH3 domains i.e. to His 435, Tyr 436 and possibly also His 433 and/or 310. Most rheumatoid factors (RF) from patients with rheumatoid arthritis show a similar binding pattern. Hence, it has been shown that antibodies to microbial IgG Fc receptors (S. aureus and group A streptococci type M15) and RF are idiotypic-anti-idiotypic antibody "partners" i.e. that RF are the "internal images" of microbial IgG Fc binding proteins. Group A streptococci possessing IgG Fc receptors elicit higher titres of RF when injected in rabbits as compared to group A streptococci without IgG Fc receptors. The streptococcal IgG Fc receptors exhibit a diversity of preferences for subclasses of human IgG, some of them showing allotype preferences. Such allotypes are also recognized by certain RF. IgG RF are able to self-associate thereby forming immune complexes which can activate the complement cascade as well as stimulate release of prostaglandins and (probably) interleukin-1. Since these factors have been assigned an important pathogenic role in rheumatoid arthritis, self-aggregating IgG RF, proposed to be induced by microbial IgG Fc receptors might be an important pathogenic factor in rheumatoid arthritis because rheumatoid arthritis is the only known condition where synthesis of RF takes place in the synovia.

“…The binding tests were performed as previously described [6]. In brief, 50 pi (2 pg) radiolabelled IgG or RF was added to a 200-pl suspension of 2 x 109 bacteria, unless otherwise stated.…”

Section: Binding Testsmentioning

confidence: 99%

“…On the other hand, we have also recently demon strated a direct binding of some RFs to group A, C and G streptococci [6]. Although this binding was exerted by IgG Fc receptor-positive streptococci, it was indicated that it took place at sites other than the IgG Fc receptors.…”

mentioning

confidence: 92%

Molecular Interactions between Human IgG, IgM Rheumatoid Factor and Streptococcal IgG Fc Receptors

Int Arch Allergy Immunol

Gharavi²,

Christensen³

1988

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Group A streptococci type M15 were previously shown to bind both human IgG via the Fc component and a purified monoclonal IgM kappa rheumatoid factor (IgM RF). Using ¹²⁵I-labelled IgG and ¹²⁵I-la-belled IgM RF, the present study gave association constants of 2.2 × 10⁷ and 2.9 × 10⁸M^––1respectively. The binding of ¹²⁵I-IgG to the streptococci was inhibited by unlabelled IgG, IgG Fc and fragment D of staphylococcal protein A but not by the IgM RFor F(ab′)₂ of anti-idiotype antibodies to RF (anti-Id RF). Inversely, unlabelled IgM RF and anti-Id RF inhibited the binding of ¹²⁵I-IgM RF markedly and unlabelled human IgG and IgG Fc only slightly or moderately, respectively. Thus, group A streptococci type M15 showed different binding sites for IgG Fc and the antibody combining sites of a human monoclonal RF. The findings were still more complex on a background of previous reports showing that streptococcal IgG Fc receptors and RFs bind to the same amino acids on the Fc molecule. This complex pattern may play a role in the pathogenesis of rheumatoid arthritis.