IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinated antigens in RA.
OBJECTIVE
Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres.


METHODS
Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates.


RESULTS
Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4.


CONCLUSIONS
Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.
Engelmann
R
R
Institute of Immunology, University of Rostock, Schillingallee 70, 18055 Rostock, Germany. robby.engelmann@med.uni-rostock.de
Brandt
J
J
Eggert
M
M
Karberg
K
K
Krause
A
A
Neeck
G
G
Mueller-Hilke
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D014746:Vimentin / Q000276:immunology
D000914:Antibodies, Viral; D001323:Autoantibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide