Human platelet antigen (HPA)‐1a peptides do not reliably suppress anti‐HPA‐1a responses using a humanized severe combined immunodeficiency (SCID) mouse model

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs most frequently when human platelet antigen (HPA)‐1a‐positive fetal platelets are destroyed by maternal HPA‐1a immunoglobulin (Ig)G antibodies. Pregnancies at risk are treated by administration of high‐dose intravenous Ig (IVIG) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating some allergic and autoimmune diseases. The HPA‐1a/1b polymorphism is Leu/Pro33 on β3 integrin (CD61), and the anti‐HPA‐1a response is restricted to HPA‐1b1b and HLA‐DRB3*0101‐positive pregnant women with an HPA‐1a‐positive fetus. We investigated whether or not HPA‐1a antigen‐specific peptides that formed the T cell epitope could reduce IgG anti‐HPA‐1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells (PBMC) in blood donations from HPA‐1a‐immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient (SCID) mice with peptides and HPA‐1a‐positive platelets. Human anti‐HPA‐1a in murine plasma was quantitated at intervals up to 15 weeks. HPA‐1a‐specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA‐1a peptides in vitro, stimulation of anti‐HPA‐1a responses by these peptides occurred in vivo. However, with a second donation from one of these women which, uniquely, had high HPA‐1a‐specific T cell proliferation in vitro, marked suppression of the anti‐HPA‐1a response by HPA‐1a peptides occurred in vivo. HPA‐1a peptide immunotherapy in this model depended upon reactivation of HPA‐1a T cell responses in the donor. For FNAIT, we suggest that administration of antigen‐specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies.