Anti-Fc gamma receptor autoantibodies from patients with Sjögren's syndrome do not react with native receptor on human polymorphonuclear leukocytes

Abstract Sera from patients with primary Sjoen's syndrome (pSS) have been examined for the presence of cell-free Fc-gamma receptor (FcγR) IIIb, which is expressed in polymorphonuclear leukocytes (PMN), and the production of related autoantibody. Sera from 66 patients with pSS were evaluated by an ELISA using recombinant human FcγRIIIb as the substrate and by flow cytometry. Cell-free FcγRIIIb was also detected by an ELISA. The fine specificity of autoantibodies was established by inhibition with a preparation of FcγRI plus FcγRII, and two ELISAs using FcγRI and FcγRII as the substrates respectively. Anti-FcγRIIIb activity was found in 30 patients (45%), but 25 of them did not react with autologous PMN, whereas they bound to FcγRIIIb eluted from the same PMN in ELISA and Western blotting. Autoantibodies from one serum recognized the three receptors, six with FcγRII in addition to FcγRIII, and three sera were specific for the latter receptor. None of these reacted with FcγRI- and FcγRII-carrying cells. Cell-free FcγRIIIb, but negligible amounts of FcγRIIIa, were detectable in the patient sera. The membrane expression of CD15, an early activation marker, was diminished, while that of three PMN late activation markers was markedly enhanced. Taken together, these results suggest that autoantibodies are produced following the shedding of FcγRIIIb upon PMN activation. A credible candidate for this activation is IgG-containing immune complexes.