Anti-interleukin-1 alpha autoantibodies in humans: characterization, isotype distribution, and receptor-binding inhibition--higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia).
Since autoantibodies (Abs) to cytokines may modify their biologic activities, high-affinity binding factors for interleukin-1 alpha (IL-1 alpha BF) were characterized in human sera. IL-1 alpha BF was identified as IgG (1) by sucrose density-gradient centrifugation followed by immunodiffusion autoradiography, (2) by ligand-blotting method, (3) by ligand binding to affinity-immobilized serum IgG, and (4) by IgG affinity purification followed by sucrose density-gradient centrifugation. IL-1 alpha binding activity resided in the F(ab)2 fragment. The apparent equilibrium constant was in the range of IgG found after immunization with conventional antigens (i.e., 10(-9) to 10(-10) mol/L). Anti-IL-1 alpha IgG auto-Abs represented only an extremely small fraction of total IgG (less than 1/10(-5)). Some sera with IL-1 alpha BF and purified IgG thereof were able to inhibit by 96% to 98% the binding of human recombinant IL-1 alpha to its receptor on murine thymoma EL4-6.1 cells, whereas other sera did not. When 125I-labeled anti-IL-1 alpha IgG complexes were injected into rats, they prolonged the plasma half-life of 125I-labeled IL-1 alpha several fold and altered its tissue distribution. The predominant class was IgG (12/19), mainly IgG4 (9/19), but in five of the sera, anti-IL-1 alpha IgA was also detected. In a screening of 271 sera, IL-1 alpha BF was detected in 17/98 normal subjects and was not more frequent in several control groups of patients, except in patients with Schnitzler's syndrome (fever, chronic urticaria, bone pain, and monoclonal IgM paraprotein) (6/9; p less than 0.005). The pathologic significance of these auto-Abs remains to be determined.
Saurat
J H
JH
Department of Dermatology, University Hospital, Geneva, Switzerland.
Schifferli
J
J
Steiger
G
G
Dayer
J M
JM
Didierjean
L
L
D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D014581:Urticaria / Q000276:immunology*; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1