Human platelet antigen (HPA)-1a peptides do not reliably suppress anti-HPA-1a responses using a humanised SCID mouse model.

Clinical and experimental immunology

PubMedID: 24261689

Jackson DJ, Eastlake JL, Kumpel BM. Human platelet antigen (HPA)-1a peptides do not reliably suppress anti-HPA-1a responses using a humanised SCID mouse model. Clin Exp Immunol. 2013;.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) most frequently occurs when human platelet antigen (HPA)-1a-positive fetal platelets are destroyed by maternal HPA-1a IgG antibodies. Pregnancies at risk are treated by administration of high dose 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 ß3 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 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. PBMC in blood donations from HPA-1a-immunised women were injected i.p. into 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 that 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 on 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.