Anti‐platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications

Abstract

Background: Anti-platelet antibody testing may be useful for the diagnosis and management of childhood immune thrombocytopenia (ITP).Objectives: Here we aimed to assess the prevalence and prognostic significance of anti-platelet glycoprotein-specific IgM and IgG antibodies. Methods:Children with newly diagnosed ITP were included at diagnosis and randomized to an intravenous immunoglobulins (IVIg) or careful observation group (TIKI trial). In this well-defined and longitudinally followed cohort (N = 179), anti-platelet glycoprotein-specific IgM and IgG antibodies were determined by monoclonal antibody-immobilization of platelet antigens. Results:The dominant circulating anti-platelet antibody class in childhood ITP was IgM (62% of patients); but IgG antibodies were also found (10%). Children without IgM platelet antibodies were older and more often female. There was weak evidence for an association between IgM anti-GP IIb/IIIa antibodies and an increased bleeding severity (P = .03). The IgM and IgG anti-platelet responses partially overlapped, and reactivity was frequently directed against multiple glycoproteins. During 1-year follow-up, children with IgM antibodies in the observation group displayed a faster platelet recovery compared to children without, also after adjustment for age and preceding infections (P = 7.1 × 10 −5 ). The small group of patients with detectable IgG anti-platelet antibodies exhibited an almost complete response to IVIg treatment (N = 12; P = .02), suggesting that IVIg was particularly efficacious in these children. Conclusions:Testing for circulating anti-platelet antibodies may be helpful for the clinical prognostication and the guidance of treatment decisions in newly diagnosed childhood ITP. Our data suggest that the development of even more sensitive tests may further improve the clinical value of antibody testing. | 1211SCHMIDT eT al. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section.

Age at Diagnosis Shapes the Prognosis of Childhood Immune Thrombocytopenia

“…Antibodies were determined by glycoprotein-specific analysis for GP Ib/IX, IIb/IIIa and V using MAIPA, as previously described. [19] The 25 th , 50 th , and 75 th quantiles (Q1-Q3) were 2, 4 and 7 years.…”

“…The presence of circulating anti-platelet antibodies was evaluated by monoclonal antibody-specific immobilization of platelet antigens (MAIPA; glycoprotein-specific) as previously described. [19] Lymphocyte subset immune phenotyping was performed in a centralized laboratory by flow cytometry (Sanquin Immunodiagnostics), using multicolour staining (BD Biosciences; Vianen, The Netherlands; #644611) in TruCount tubes (BD Biosciences #340334) on heparinized whole blood. Thrombopoietin was measured using an in-house ELISA [20,21] and expressed in arbitrary units (AU/mL), where one AU is equal to 9 pg of recombinant TPO (Research Diagnostics, Flanders, NJ, USA).…”

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

“…This finding is in accordance with a recent Danish study, in which PA-IgM were significantly more frequent than PA-IgG in children with ITP (63% vs. 44%, P = 0.03) ( 15 ). Schmidt et al have also reported that anti-platelet antibodies were predominantly of the IgM class in children with newly diagnosed ITP ( 16 ). In the same study, the authors have noted that IgM responses were present short term without evidence of class-switching to IgG ( 16 ).…”

“…Schmidt et al have also reported that anti-platelet antibodies were predominantly of the IgM class in children with newly diagnosed ITP ( 16 ). In the same study, the authors have noted that IgM responses were present short term without evidence of class-switching to IgG ( 16 ). Such responses are likely to be triggered by infections, and molecular mimicry may play a central role in the development of self-directed anti-platelet immunity ( 17 , 18 ).…”

“…Such responses are likely to be triggered by infections, and molecular mimicry may play a central role in the development of self-directed anti-platelet immunity ( 17 , 18 ). Furthermore, a pathophysiological role of IgM anti-platelet antibodies in ITP has been demonstrated ( 16 , 19 ). Unlike IgM anti-erythrocyte autoantibody that promotes anemia through a massive agglutination of RBCs in spleen and liver, PA-IgM induces thrombocytopenia through uptake of opsonized platelets ( 19 , 20 ).…”