IgG autoAbs Research Articles

Spectrum of Ig Classes, Specificities, and Titers of Serum Antiglycoproteins in Chronic Idiopathic Thrombocytopenic Purpura

AbstractThe characteristic decreased recovery and survival of transfused platelets in non-alloimmunized patients with idiopathic thrombocytopenic purpura (ITP) suggest that plasma antiplatelet autoantibodies (autoAbs) are present in almost all cases. Studies emphasizing reactions of IgG autoAbs with platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP patients have detectable serum Abs, and that many of these Abs may not be pathogenic because they are directed against epitopes in the cytoplasmic domain of GPIIIa (Fujisawa et al. Blood 77:2207, 1991 and 79:1441, 1992). We evaluated the contribution of Ig classes other than IgG to the overall incidence of serum Abs in 47 patients with chronic ITP and the frequency of reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further characterized by their reactions with cytosolic or exosolic GP epitopes and their titers and apparent affinities. Using immunobead techniques we found (1) anti-GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in 51 %; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81 %, 38%, and 28% of cases, respectively; (5) 93% of positive sera reactive with more than one GP; but GP IV or la/IIa never the sole target; (6) Abs against cytosolic epitopes on one or more of GPs IIIa, Voa. and IIbβ in 66% of sera, always accompanied by Abs against exosolic epitopes of the same or a different GP; (7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered from posttransfusion purpura and drug purpura; and (8) evidence that serum ITP Abs, often high-titered, saturate platelets less than alloAbs against the same GPs. Whereas Abs against external GP epitopes are a distinctive marker for ITP in 80% of patients, Abs against internal GP epitopes are likely a secondary phenomenon of platelet destruction and not pathogenic. Anti-GPs against exosolic epitopes were also found in eluates of patient’s platelets, suggesting that they have pathogenic significance.

Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura

The characteristic decreased recovery and survival of transfused platelets in nonalloimmunized patients with idiopathic thrombocytopenic purpura (ITP) suggest that plasma antiplatelet autoantibodies (autoAbs) are present in almost all cases. Studies emphasizing reactions of IgG autoAbs with platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP patients have detectable serum Abs, and that many of these Abs may not be pathogenic because they are directed against epitopes in the cytoplasmic domain of GPIIIa (Fujisawa et al, Blood 77:2207, 1991 and 79:1441, 1992). We evaluated the contribution of Ig classes other than IgG to the overall incidence of serum Abs in 47 patients with chronic ITP and the frequency of reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further characterized by their reactions with cytosolic or exosolic GP epitopes and their titers and apparent affinities. Using immunobead techniques we found (1) anti- GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in 51%; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81%, 38%, and 28% of cases, respectively; (5) 93% of positive sera reactive with more than one GP; but GP IV or Ia/IIa never the sole target; (6) Abs against cytosolic epitopes on one or more of GPs IIIa, Ib alpha, and IIb beta in 66% of sera, always accompanied by Abs against exosolic epitopes of the same or a different GP; (7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered from posttransfusion purpura and drug purpura; and (8) evidence that serum ITP Abs, often high-titered, saturate platelets less than alloAbs against the same GPs. Whereas Abs against external GP epitopes are a distinctive marker for ITP in 80% of patients, Abs against internal GP epitopes are likely a secondary phenomenon of platelet destruction and not pathogenic. Anti-GPs against exosolic epitopes were also found in eluates of patients platelets', suggesting that they have pathogenic significance.

Anti-interleukin-1α 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-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.