An Fc gamma RIII (CD16)-specific autoantibody from a patient with progressive systemic sclerosis.
Polyspecific and organ specific autoimmune diseases are often accompanied by prolonged clearance of immune complexes. In mice, impaired macrophage Fc gamma receptor function may be associated with autoantibody against Fc gamma receptors. To extend these observations to autoimmune human disease, we transformed with EBV peripheral lymphocytes from a patient with terminal progressive systemic sclerosis and screened for clones secreting anti-Fc gamma receptor Ig. A clone, N55, which secretes a high affinity anti-Fc gamma receptor IgG2 antibody was obtained. The Fab fragment of N55 bound to human neutrophils, NK cells, but not to monocytes, consistent with specificity for Fc gamma RIII (CD16). N55 Fab competed weakly for the binding of anti-Fc gamma RIII mAb 3G8 to neutrophils but did not have any effect on staining with the anti-Fc gamma RII mAb, IV.3. N55 Fab did not bind to peripheral monocytes, but did bind to monocytes incubated with TGF-beta (24 h) to induce Fc gamma RIII. The specificity of N55 IgG for Fc gamma RIII was confirmed by ELISA using secreted recombinant Fc gamma RIIA and Fc gamma RIIIB protein to coat microtiter wells. N55 IgG triggered the release from neutrophils of beta-glucuronidase, arylsulfatase and alkaline phosphatase. Such antibody may play a pathogenic role in progressive systemic sclerosis.
Department of Biochemistry, Mount Sinai School of Medicine, New York City, NY 10029.
A
A
Szegedi
P
P
Boros
J
J
Chen
M
M
Kaffina
C
C
Bona
J C
JC
Unkeless
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000918:Antibody Specificity; D001192:Arylsulfatases / Q000096:biosynthesis; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002472:Cell Transformation, Viral; D005966:Glucuronidase / Q000096:biosynthesis; D004854:Herpesvirus 4, Human; D006801:Humans; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D017452:Receptors, IgG; D012595:Scleroderma, Systemic / Q000201:enzymology / Q000209:etiology / Q000276:immunology*
D001323:Autoantibodies; D017452:Receptors, IgG; D000469:Alkaline Phosphatase; D001192:Arylsulfatases; D005966:Glucuronidase