ANTI-INTERLEUKIN-1-ALPHA AUTOANTIBODIES IN HUMANS - CHARACTERIZATION, ISOTYPE DISTRIBUTION, AND RECEPTOR-BINDING INHIBITION - HIGHER FREQUENCY IN SCHNITZLER 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 (< 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 I-125-labeled anti-IL-1-alpha-IgG complexes were injected into rats, they prolonged the plasma half-life of I-125-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 < 0.005). The pathologic significance of these auto-Abs remains to be determined.