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.