A recent study published in Blood Advances has revealed that the incubation of immune thrombocytopenia (ITP) serum with normal donor platelets triggers platelet consumption through macrophage phagocytosis for half of the patients with ITP sera.
The research found that platelet autoantibody, increased serum pentraxin 3, and reduced platelet count, were associated with increased macrophage phagocytosis.
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The study assessed the sera from a cohort of 24 patients with ITP at Sunnybrook Health Sciences Centre and an additional 152 patients at University Health Network and the Canadian Blood Services. The assessment investigated the ability to stimulate macrophage phagocytosis of normal donor platelets and characterize the contribution of humoral factors associated with phagocytosis.
The phagocytosis was considered positive if the sera that produced a phagocytosis magnitude greater than a normal human serum were detected during the analysis. Altogether, 42% of ITP sera were found phagocytosis positive.
For the detection of IgG autoantibodies to GP2b/3a, GP1b/9, and GP1a/2a, the indirect monoclonal antibody immobilization of platelet antigens assay was used.
Study results showed that the autoantibody positive sera triggered a greater mean magnitude of phagocytosis than the negative sera. Moreover, an inverse correlation was found between the phagocytosis and platelet counts among the autoantibody positive patients but not in the autoantibody negative patients.
The reassessment results of phagocytosis showed that phagocytosis was primarily sustained in the purified IgG fractions, indicating that patients with ITP with platelet associated IgG3 seem to have more severe thrombocytopenia than patients with platelet associated IgG4. In addition, the demonstration of pentraxin 3 as a potential phagocytosis modulator was found effective, suggesting a key role for antiplatelet autoantibodies in phagocytosis.
“We observed an inverse correlation between pentraxin 3 serum concentration and platelet counts among autoantibody positive patients, which may serve as an impetus for future investigation into pentraxin 3 and ITP pathophysiology” the authors highlighted.
ITP is a bleeding disorder with an unusually low platelet count (below 100,000/µL). The accelerated clearance of platelets is a central feature of ITP where the white blood cell and hemoglobin levels are normal, and patients experience a generalized purpuric rash.
Antiplatelet autoantibodies are thought to alter platelets and trigger clearance by macrophage phagocytosis, specifically in the spleen, a dominant site of platelet clearance in ITP. Current understanding suggests that autoantibodies against multiple platelet antigens, such as GP2b/3a, GP1b/9, GP5, and GP1a/2a, are involved in ITP.
While it is widely accepted that thrombocytopenic factors, such as autoantibodies, can cause macrophage phagocytosis-mediated platelet clearance in ITP, a number of studies have reported that the incubation of healthy donor platelets with splenic leukocytes from patients with ITP results in significant platelet uptake. These studies provide evidence that platelets from patients with ITP or healthy donor platelets incubated with ITP sera or plasma are internalized by phagocytes at a higher level than in normal controls.
Reference
Norris PAA, Tawhidi Z, Sachs UJ, et al. Serum from half of immune thrombocytopenia patients trigger macrophage phagocytosis of platelets. Blood Advances. Published online April 12, 2023. doi:10.1182/bloodadvances.2022009423
