a Other: other specificities with antibodies with MIF higher than 1000: B78, B35, B53, B18, B72, B55, B76, B56, B42, B67, B37 and B62.
Discussion
Anti-HLA antibodies are very common in the serum of pregnant women. Approximately 7%-39% of pregnant women develop anti-HLA antibodies. With the development of technology, 49.3% of pregnant women with antibodies can be detected with the more sensitive Luminex method[6]. In 18-30% of pregnant women with multiple pregnancies, anti-HLA antibodies can be detected[7]. While anti-HLA antibodies rarely cause FNAIT or ANN, whether anti-HLA antibodies can be considered the cause of FNAIT/ANN is still controversial. Several theories[8-11] have been postulated to address this discrepancy, such as differential placental absorption, reduced HLA expression on neonatal cells, or binding of alloantibodies to fetal macrophages resulting in inhibition of fetal platelet destruction. However, we report here a very unusual case of a first twin pregnancy produced in vitro fertilization by oocyte and semen donation; the two oocytes were from two donors. HLA-incompatible twin pregnancy due to oocyte donation might have contributed to the high median fluorescence intensity of the mother’s antibodies, which were homozygous for class I HLA antigens.
Lashley et al.[12] found that HLA compatibility between donors and recipients could be relevant for the survival of fetal allografts in OD pregnancy, and they observed a significantly higher degree of HLA matching between mothers and children in uncomplicated OD pregnancies than expected, suggesting that HLA compatibility might be beneficial for the development of successful and uncomplicated OD pregnancies. In our case, the two oocytes carrying the HLA genotype may be completely different, which is why infant 1 did not show symptoms of thrombocytopenia. We hypothesize that the HLA between mother and infant 1 is more compatible than that between infant 2. However, the family members refused to test for HLA and antibodies in infant 1.
Although anti-HLA antibody-mediated FNAIT/ANN is a diagnosis of exclusion and difficult to confirm, the correlation in the case is strong enough. The immunohematological investigation found no anti-HPA and anti-HNA antibodies in the mother’s serum or in infant 2. However, we found anti-HLA-A2, anti-HLA-A24 and anti-HLA-68 antibodies in both the mother’s serum and infant 2. The surfaces of platelets and neutrophils do have the same HLA. We believe that the anti-HLA antibodies may be the reason for FNAIT and ANN in infants. IVIG transfusion is effective in increasing platelet and neutrophil counts.G-CSF was not given in the NICU. The infant’s inflammatory indicators were not increased, blood bacterial culture was also negative, and the possibility of infection was not considered.
Dahl[13] showed that thrombocytopenic neonates born to mothers with anti-HLA class I antibodies had a significantly lower birth weight than controls. An increasing level of maternal anti-HLA class I antibodies was linearly and inversely associated with birth weight and placental weight among thrombocytopenic neonates. The birth weight of infant 2 was 2060 g, which is a low birth weight infant (LBWI). However, the birth weight of infant 1 was 3240 g. These results may explain the difference.
Anemia occurred in infant 2 in the NICU. HLA antibody-induced ANN and/or NAIT are characterized by the absence of anemia, as mature erythrocytes do not present HLAs. The direct antiglobulin test (DAT) was positive, and anemia occurred after treatment with piperacillin sodium and tazobactam sodium for three days. Anti-piperacillin sodium and tazobactam sodium antibodies were detected, and hemolysis of the infant was confirmed to be drug-induced hemolytic anemia (DIHA). The direct antiglobulin test (DAT) is invaluable for classifying the cause of RBC destruction as immune or nonimmune[14]. Renard D[15] reported that the incidence of DIHA is approximately only 1 per million/year, but penicillins and cephalosporins are frequent causes of DIHA based on a review of case reports from 2010–2016. This review also examined the probability of DIHA, and several core elements must be taken into account: chronological sequence, epidemiological data, objective evidence, and differential diagnosis. Corticosteroids and IVIG are effective in treating anemia.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
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