Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

Abstract

SUMMARYThe objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins and by immunoblotting of electrophoretically separated cell, granule or nuclear extracts. Forty-two sera (68%) reacted with ethanol-fixed neutrophils. In the ELISAs 32% of the 28 medium to strongly IIF-positive sera were negative, while 43% were weakly positive for more than one antigen. Immunoblots of whole neutrophils showed IgG reactions at 25-35 kD, in the 55-kD region, at 80 kD, and at 110kD. Most sera reacted with more than one band. Except for the 55-kD antigen, none of the antigens appeared in lymphocytes. The most notable reactivity in subcellular fractions was with lactofemn and with bands of 25-35 kD from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactofemn is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved.

International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA)

“…These include a-enolase, 33 catalase, 34 highmobility-group nonhistone chromosomal proteins, 35 actin, 36 cathepsin G, 37 elastase, 31 lactoferrin, 38 lysozyme, 39 and other unidentified targets. 40 With ANCA in which the specificities are not PR3 or MPO, antibody levels are variable but often low, and there usually is no clear correlation with disease activity or other clinical variables.…”

Anti-neutrophil Cytoplasmic Antibodies Tests: Which Tests Should be Used in Practice?

“…If atypical ANCAis reported to clinicians it is essential to mention in the laboratory report that this does not in itself indicate that a patient has SSVV. Atypical ANCApatterns are very often due to the presence of autoantibodies to multiple neutrophil antigens (24). If strong BPI-ANCAis found in serum it may well indicate vasculitis related to an infectious etiology such as subacute bacterial endocarditis or chronic pseudomonasinfection in cystic fibrosis or bronchiectasia patients (23).…”

Citrullination in Rheumatoid Arthritis—A Process Promoted by Neutrophil Lysis?

“…Research conducted by Starkebaum and colleagues at the University of Washington33–36 revealed that ICs, in particular IgG targeting neutrophils, are present in RA synovial fluid (SF) and mediate neutrophil activation. Although the literature contains conflicting data regarding the nature and prevalence of anti-neutrophil-binding IgG in RA depending on the method used for analysis of antigenic targets,33,34,37,38 it is estimated that IgG-containing ICs as well as complement C3 activation fragments can be found in the joints of >90% of RA patients 39,40…”