Intravenous (IV) anti‐D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti‐D by FcγRIIa and FcγRIIIa polymorphisms
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SummaryIntravenous (IV) anti‐D and IV immunoglobulin (IVIG) slow the Fcγ receptor (FcγR)‐mediated destruction of antibody‐coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin‐10 (IL‐10), monocyte chemoattractant protein‐1 (MCP‐1), IL‐6 and tumour necrosis factor α (TNFα), before and after infusion and by assessing the effect of FcγRIIa and FcγRIIIa polymorphisms on both cytokine and haematologic responses to anti‐D. Following IVIG, only IL‐10 was increased at 2 h and MCP‐1 on day 7 (P < 0·05). In contrast, 2 h after anti‐D infusion, plasma levels of all four cytokines were increased (P < 0·01); five of six patients with the highest MCP‐1, IL‐6 and TNFα levels had chills. Higher IL‐10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 (P < 0·025). Patients with the FcγRIIa‐131HH genotype had significantly higher MCP‐1, IL‐6 and TNFα levels. Patients with the FcγRIIIa‐158VF genotype had higher platelet increments at day 7 (P < 0·05). Soluble CD16 (sCD16) was increased 2 h after IV anti‐D; day 7 levels correlated with day 7 haemoglobin decreases (P < 0·01). In conclusion, the relationship of FcγRIIa and FcγRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti‐D and supported different mechanisms of FcγR interaction to those seen with IVIG.
