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

Abstract

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.

Immunoglobulins targeting both GPIIb/IIIa and GPIb/IX in chronic idiopathic thrombocytopenic purpura (ITP): evidence for at least two different IgG antibodies

“…From these findings we concluded that these ITP sera, reactive with both GPIIb/IIIa and GPIb/IX, held at least two different IgG antibody populations, each reactive with only one of the GP complexes. Similar findings can be deducted from a recent report by He et al (1994). Employing the immunobead assay, these authors detected eight ITP sera reactive with both GPIIIa and GPIb/IX.…”

“…In summary, our present study and one previous report have provided evidence that ITP sera reactive with both GPIIb/IIIa and GPIb/IX hold at least two different plateletspecific antibody populations. Also, antibodies specific for GPIa/IIa, GPIV, GPV, and some intracellular structures have been demonstrated in chronic ITP (Tomiyama et al, 1992;He et al, 1994;Hou et al, 1996). All these findings implicate that, in some cases of chronic ITP, the spectrum of platelet autoantigens can diversify.…”

Anti‐CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen

“…In addition to TTP plasmas, a close correlation was also found between the PAICA and immunoblots for detecting anti-CD36 antibodies in plasmas of patients with ITP: 20% were detected with PAICA and 19% with immunoblots. He et al (1994), using mAb FA6-152 and antigen capture methods, found antibodies to GPIV (CD36) in 38% of 47 patients with chronic ITP. The form of CD36 was not investigated.…”

Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura

“…Platelet‐associated IgG (PAIgG) is thought to be an important factor in the mechanism of ITP, since increase in PAIgG is closely related to reduced platelet count in this disease (14–16). Although the platelet surface antigens corresponding to the anti‐platelet autoantibodies involved in ITP are largely unknown, there have been several recent reports on autoantibodies to glycoprotein (GP) IIb/IIIa and GPIb (17–19), and the antigens to these GPs are gradually being determined (20). There are some platelet‐reactive T cells in patients with ITP (21), and GPIIb/IIIa is one of the major target antigens recognized by platelet‐reactive CD4 + T cells (22).…”