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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Abstract
Intravenous (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.