Anti-Fc gamma receptor autoantibodies from patients with Sjögren's syndrome do not react with native receptor on human polymorphonuclear leukocytes.
Sera from patients with primary Sjögren's syndrome (pSS) have been examined for the presence of cell-free Fc-gamma receptor (Fc gamma R) 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 Fc gamma RIIIb as the substrate and by flow cytometry. Cell-free Fc gamma RIIIb was also detected by an ELISA. The fine specificity of autoantibodies was established by inhibition with a preparation of Fc gamma RI plus Fc gamma RII, and two ELISAs using Fc gamma RI and Fc gamma RII as the substrates respectively. Anti-Fc gamma RIIIb activity was found in 30 patients (45%), but 25 of them did not react with autologous PMN, whereas they bound to Fc gamma RIIIb eluted from the same PMN in ELISA and Western blotting. Autoantibodies from one serum recognized the three receptors, six with Fc gamma RII in addition to Fc gamma RIII, and three sera were specific for the latter receptor. None of these reacted with Fc gamma RI- and Fc gamma RII-carrying cells. Cell-free Fc gamma RIIIb, but negligible amounts of Fc gamma RIIIa, 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 Fc gamma RIIIb upon PMN activation. A credible candidate for this activation is IgG-containing immune complexes.
Lamour
A
A
Laboratory of Immunology, Brest Medical School Hospital, France.
Le Corre
R
R
Soubrane
C
C
Khayat
D
D
Youinou
P
P
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D017452:Receptors, IgG; D011994:Recombinant Proteins