Positive neonatal direct antiglobulin test and free circulating panagglutinin due to high-titer immunoglobulin G1 anti-Inb without in vivo hemolysis.

BACKGROUND: The cluster of differentiation 44 glycoprotein carries the Indian blood group system, including the antithetical antigens Ina and Inb. The Inb antigen is highly prevalent, with more than 99.9% of Caucasians being Inb-positive, whereas Inb-negative individuals are found almost exclusively in South Asian populations (~0.02%). Anti-Inb can cause hemolytic transfusion reactions, but little data are available on hemolytic disease of the fetus and newborn (HDFN), suggesting minimal placental transfer, with only one reported case of a positive neonatal direct antiglobulin test (DAT). CASE REPORT: A woman of Indian origin developed an anti-Inb alloantibody with a titer of 64 during her first pregnancy. This was detected only at delivery, with no evidence of transplacental transfer of antibodies or HDFN. The anti-Inb titer increased after delivery, reaching a peak of 1024, and remained stable throughout the second pregnancy. At birth, the second neonate showed a strongly positive DAT, with anti-Inb detectable in both the plasma and eluate, confirming transplacental transfer and red blood cell binding. Testing of maternal plasma showed immunoglobulin G1 predominance over immunoglobulin G3 and moderate-to-high hemolytic potential in the monocyte monolayer assay and antibody-dependent cellular cytotoxicity (ADCC) test, with a monocyte index of 7.7-10% and ADCC of ~40%. Despite these findings, the neonate exhibited no signs of hemolysis. CONCLUSION: This case demonstrates that high-titer, functionally active maternal anti-Inb antibodies can coexist with neonatal anti-Inb reactivity without causing hemolysis. The marked discrepancy between serological, functional, and clinical findings underscores the limited predictive value of current assays in rare blood group incompatibilities.