Prevalence and clinical significance of low-avidity HPA-1a antibodies in women exposed to HPA-1a during pregnancy (original) (raw)

BACKGROUND-Recent studies suggest that HPA-1a-specific, low-avidity maternal antibodies not detectable by conventional methods can cause neonatal alloimmune thrombocytopenia (NAIT). We performed studies to further define the incidence and clinical significance of this type of antibody. STUDY DESIGN AND METHODS-Surface plasmon resonance analysis was used to detect low-avidity antibodies in HPA-1a-negative, "antibody-negative" mothers of suspected NAIT cases. The ability of antibodies detected to promote immune destruction of human platelets (PLTs) was examined in a newly developed NOD/SCID mouse model. RESULTS-Among 3478 suspected cases of NAIT, 677 HPA-1a-negative mothers were identified. HPA-1a-specific antibodies were detected by conventional antibody testing in 616 cases (91%). Low-avidity HPA-1a-specific antibodies were identified in 18 of the remaining 61 cases (9%). Clinical follow-up on 13 cases showed that eight were referred because of suspected NAIT and five because the mother's sister had previously had an infant with NAIT. Only six infants born to the 13 sensitized mothers had clinically significant thrombocytopenia at birth. Three of four low-avidity antibodies tested in the mouse caused accelerated clearance of HPA-1a/a but not HPA-1b/b PLTs. Only 3 of 12 mothers with low-avidity HPA-1a antibodies were positive for HLA-DRB3*0101. CONCLUSIONS-The findings confirm previous reports that low-avidity HPA-1a antibodies can cause NAIT but show that the presence of such an antibody does not predict that an infant will be affected. The low incidence of HLA-DRB3*0101 in this cohort (p < 0.0001) suggests that women negative for DRB3*0101 may be predisposed to produce low-avidity HPA-1a antibodies. Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal immunization against platelet (PLT)-specific antigens inherited by a fetus from its father, occurs once in approximately 1000 births. 1-3 Although many cases are mild, approximately half of the affected infants have bleeding symptoms and up to 10% experience intracranial hemorrhage. 4,5 The first human PLT antigen (HPA) shown to be capable of triggering maternal antibodies and causing NAIT was HPA-1a (originally called Pl A1) described by Shulman and colleagues in 1962. 6 Since that time, at least 27 different HPA antigens have been implicated in NAIT. 7-14 However, fetal-maternal incompatibility for HPA-1a continues to be the most common cause of this disorder, even though only approximately