IgG Rheumatoid Factors Against the Four Human Fc‐gamma Subclasses in Early Rheumatoid Arthritis (The Swedish TIRA Project)

Abstract

Rheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG‐RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG‐RFs directed against the four IgG subclasses. IgG‐RF against either subclass of human IgG‐Fc were analysed with four novel enzyme‐linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc‐gamma fragments (hIgG1–4) as sources of antigen. Sera from 40 patients with recent onset RA (20 seropositive and 20 seronegative by IgM‐RF and IgA‐RF‐isotype‐specific ELISA) were analysed. Sera from 20 healthy blood donors served as reference. Among the IgM‐/IgA‐RF‐positive RA‐sera, IgG‐RF was found directed against hIgG1 and hIgG2, but not against hIgG3 or hIgG4. Significant correlations were seen between IgG‐RF against hIgG2‐Fc and IgM‐RF (r = 0.666) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.

IgG Subclass Specificity Discriminates Restricted IgM Rheumatoid Factor Responses From More Mature Anti–Citrullinated Protein Antibody–Associated or Isotype‐Switched IgA Responses

“…However, this uncovered false positivity caused by Fc–Fc interactions between IgG4 present in the test sera and the IgG‐Fc used as coating . Kanmert et al reported high levels of IgG‐RF directed against IgG1‐Fc and IgG2‐Fc in IgM‐RF+/IgA‐RF+/ACPA+ RA sera, with but it was also present in controls. Elson et al reported IgG‐RF reactivity against IgG1‐Fc and IgG2‐Fc in RA sera.…”

Development of myeloid cell-based immune profiling on microarrays

“…Our results regarding binding of heat-inactivated and native sera to spotted IgG subclasses showed good agreement with this data. Yet other investigators found substantial IgG3 reactivity in serum RF of IgG isotype, however only the level of IgG1 and IgG2 specific RF was elevated in RA samples compared to healthy samples [185]. As of note the serum RF and that from synovium shows significant difference in reactivity [186], to IgG3 as well, as the synovium derived monoclonal RFs were shown to bind IgG3 in an allotype dependent manner [187].…”

Exosomal Osteoclast-Derived miRNA in Rheumatoid Arthritis: From Their Pathogenesis in Bone Erosion to New Therapeutic Approaches

“…This phenomenon typically occurs under inflammatory conditions, and citrullinated proteins are recognized by autoantibodies called anti-citrullinated antibodies (ACPA), the presence of which in patients' serum is considered a diagnostic marker for RA [18]. Another autoantibody used as a diagnostic marker for the disease is rheumatoid factor (RF), which recognizes the crystallizable fraction (Fc) of immunoglobulins (Ig) G [19]. Both ACPA and RF are present in the serum of patients who will develop this disease years later [20].…”