A new assay uses monoclonal anti-Rh(D) antibodies to determine rheumatoid factor specificity: reactivity to a monoclonal antibody of the Gm allotype G3m(21) is more frequent in rheumatoid patients negative for G3m(21) 1988

V E Jones, and A H Puttick, and E A Williamson, and R A Mageed
Postgraduate Medical School, University of Exeter, Devon, UK.

A new method has been developed to determine the specificities of polyclonal rheumatoid factors (naturally occurring antibodies which react with human Fc gamma) (RF) found in sera from patients with rheumatoid arthritis. In this method, monoclonal anti-Rh(D) antibodies of known IgG isotype and allotype are bound to erythrocytes and then act as the target IgG antigen for RF in a direct haemagglutination test. Using two monoclonal anti-D antibodies of the IgG3 isotype and G3m(21) allotype, which were cloned from different donors, we found that a large number of rheumatoid sera reacted with both these G3m(21) proteins. In contrast reactivity of rheumatoid sera with polyclonal anti-D of the G3m(21) allotype in the direct haemagglutination test was rare. A strong correlation was found between reactivities to both G3m(21) monoclonal anti-D antibodies but not with a monoclonal anti-D antibody carrying the alternative allele, namely G3m(5). Haemagglutination inhibition experiments using human paraproteins of known IgG isotype and allotype provided some additional evidence that this method can detect RF with specificity for the G3m(21) allotypic determinant or a related allotypic determinant in polyclonal rheumatoid sera. When each patient's autoantibody response was related to their Gm phenotype, we found that the frequency of reactivity for G3m(21) monoclonal anti-D antibodies was significantly greater in patients negative for G3m(21) than in patients positive for the G3m(21) allotype. IgM preparations from patients' sera were dissociated at acid pH but no 'hidden' antibodies were found. We suggest trans-placental sensitization as one of several possible interpretations of this finding.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007075 Immunoglobulin M A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin. Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D007129 Immunoglobulin Gm Allotypes Allelic variants of the gamma-immunoglobulin heavy chain (IMMUNOGLOBULIN GAMMA-CHAINS) encoded by ALLELES of IMMUNOGLOBULIN HEAVY CHAIN GENES. Allotypes, Immunoglobulin Gm,Gm Allotypes,Ig Gm Allotypes,Allotype, Gm,Allotype, Ig Gm,Allotype, Immunoglobulin Gm,Allotypes, Gm,Allotypes, Ig Gm,Gm Allotype,Gm Allotype, Ig,Gm Allotype, Immunoglobulin,Gm Allotypes, Ig,Gm Allotypes, Immunoglobulin,Ig Gm Allotype,Immunoglobulin Gm Allotype
D007518 Isoantibodies Antibodies from an individual that react with ISOANTIGENS of another individual of the same species. Alloantibodies
D008297 Male Males
D008722 Methods A series of steps taken in order to conduct research. Techniques,Methodological Studies,Methodological Study,Procedures,Studies, Methodological,Study, Methodological,Method,Procedure,Technique
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D006386 Hemagglutination Tests Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed) Hemagglutination Test,Test, Hemagglutination,Tests, Hemagglutination
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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