Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis

Abstract

SUMMARYSertim IgG, labelling ihe straiutn corneum ofthe rat oesophagus epithelium, so-called anii-keratin antibodies (AKA) conslilule the most speciiic marker for ihe diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 conlrol sera from patients wilh non-rhcuniatoid intlammatory rheutnatic discuses. The serum level of IgG 1.2.3 and 4 was determined by radial inimunodiffusion and the subelass distribtition of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of ihe four human IgG stibelasses. In the rheumatoid sera, the serum level of IgG I was found to be signifieantiv increased and the level of lgG2 signitkaTitly decreased with regard to the control sera. while the levels of lgG3 and 4 as well its lolal IgG were in the nortnal range. lgGI.2..V and 4 AKA were detected in 27(87'Ki).6( 19'^,), 4(13''")iind 11 (35"'ii)ofthe3l rheumatoid sera, respectively, and were found to be independent of Ihe clinical and biological indices of ihe disease. In spile of inlerindividtial heterogeneity, two predominant profiles were distinguished: IgGl(alone) and lgG( I +4). which together represented 18 sera (58"n). The large predominanee of IgGI AKA and the qtiasiabsence of lgG2 AKA suggest thai the recognized anligen may be partly comprised of protein.Moreover, the high frequency of occurrence of !gG4 AKA might result from chronic exposure to the eliciting antigen, which eould be a genuine atitoantigen since we demonstrated that it is also present in ihe stratum corneum of human epidermis.

Label-free detection of immune complexes with myeloid cells

“…We observed a specific interaction of the U937 cells with the MAPs‐sensor spots after opsonization with reactive sera on‐chip. Previous studies investigating anti‐keratin antibodies , and later ACPA in samples from RA patients, revealed different isotype distribution when measured on different peptides, mainly with high IgG1‐levels and frequent IgG4‐positivity, but without IgG2 . Class‐switching is generally thought to develop before the onset of the specific spectra of symptoms characterizing RA .…”

Autoimmune Response to Post‐Translationally Modified (Citrullinated) Proteins: Prime Suspect in the Pathophysiology of Rheumatoid Arthritis

“…The isotype profile of ACPA, mainly corresponding to IgG1 frequently associated with IgG4 [103,104], is perfectly compatible with a capacity to form immune complexes able to activate complement-and Fcg receptor (FcgR)-dependent pathways, potentially leading to production of inflammatory cytokines. Fitting with this assumption is the fact that a recently developed human in vitro model demonstrated the pro-inflammatory potential of the interaction of ACPA-containing immune complexes via engagement of FcgR at the surface of rheumatoid synovial tissue macrophages [105].…”

Fingerprinting of anti-citrullinated protein antibodies (ACPA): specificity, isotypes and subclasses

“…57 Anti-citrullinated fibrinogen antibodies are also modulated by tumor necrosis factor (TNF)-blocking agents. In adalimumab-treated RA patients, AhFibA levels decrease by 14% when total IgG or IgG1 is measured and by 36% for IgG4; 58 this effect is more pronounced in the so-called 'EULAR good responders', 59 with a 48% reduction for IgG4 in this group.…”