Anti-interleukin-1α autoantibodies in humans: Characterization, isotype distribution, and receptor-binding inhibition—Higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia)

• Published in: Journal of allergy and clinical immunology Vol. 88; no. 2; pp. 244 - 256
• Main Authors: Saurat, Jean-Hilaire, Schifferli, Jürg, Steiger, Gertraud, Dayer, Jean-Michel, Didierjean, Liliane
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.08.1991
• Subjects: 550201 - Biochemistry- Tracer Techniques; 550901 - Pathology- Tracer Techniques; Aged; ANIMALS; ANTIBODIES; Autoantibodies - analysis; Autoantibodies - physiology; AUTORADIOGRAPHY; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BIOCHEMICAL REACTION KINETICS; CHEMICAL COMPOSITION; DAYS LIVING RADIOISOTOPES; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; Female; GLOBULINS; GROWTH FACTORS; Humans; IgA autoantibodies; IgG4 autoantibodies; Immunoglobulin G - analysis; Immunoglobulin G - metabolism; Immunoglobulin Isotypes - analysis; IMMUNOGLOBULINS; Interleukin-1 - immunology; Interleukin-1 - metabolism; interleukin-1 plasma clearance; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IODINE 125; IODINE ISOTOPES; Iodine Radioisotopes; ISOTOPES; KINETICS; LIGANDS; LYMPHOKINES; macroglobulinemia; Male; MAMMALS; MAN; MEMBRANE PROTEINS; Metabolic Clearance Rate; Middle Aged; MITOGENS; MONOCLONAL ANTIBODIES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PATHOGENESIS; PRIMATES; PROTEINS; RADIOISOTOPES; RATS; REACTION KINETICS; RECEPTORS; Receptors, Immunologic - metabolism; Receptors, Interleukin-1; RODENTS; Schnitzler's syndrome; SKIN DISEASES; urticaria; Urticaria - immunology; VERTEBRATES; Waldenstrom Macroglobulinemia - immunology; IL-1α BF; SS; PBS; Ab; IL-1; Schnitzler's syndrome; PAGE; TNF; PEG; rh; urticaria; IgG4 autoantibodies; K m; IgA autoantibodies; macroglobulinemia; interleukin-1 plasma clearance
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/0091-6749(91)90335-L

Since autoantibodies (Abs) to cytokines may modify their biologic activities, high-affinity binding factors for interleukin-1α (IL-1α BF) were characterized in human sera. IL-1α 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-1α 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-1α IgG auto-Abs represented only an extremely small fraction of total IgG ( <1 10 −5 ). Some sera with IL-1α BF and purified IgG thereof were able to inhibit by 96% to 98% the binding of human recombinant IL-1α to its receptor on murine thymoma EL4-6.1 cells, whereas other sera did not. When 125I-labeled anti-IL-1α IgG complexes were injected into rats, they prolonged the plasma half-life of 125I-labeled IL-1α 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-1α IgA was also detected. In a screening of 271 sera, IL-1α 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.