First Example of Hemolytic Disease of the Newborn Caused by Anti-Or and Confirmation of the Molecular Basis of Or

Abstract

Background and Objectives: The rare MNS antigen Or (MNS31) is sensitive to ficin, papain and sialidase, but partially resistant to trypsin (0.05%); the effect of α-chymotrypsin is not known. A point mutation, 204C → T in exon 3 of GYPA, is associated with the Or+ phenotype. We report here the first case of hemolytic disease of the newborn (HDN) caused by anti-Or, and expand the information on the nature of the Or determinant. Materials and Methods: A woman, gravida 4, para 0, delivered a baby whose red blood cells (RBCs) were positive (2+) on the direct antiglobulin test (DAT). The mother’s serum, an eluate made from the baby’s RBCs and the RBCs of the baby’s father were investigated. Exon 3 of GYPA, extracted from the father’s genomic DNA, was amplified and sequenced. Results: The mother’s serum reacted at room temperature, 37°C and on the indirect antiglobulin test with RBCs from the baby’s father. The father’s RBCs were M+N+S–s+Or+. The antibody in the mother’s serum and in the baby’s eluate was identified as anti-Or. The serum did not react with the father’s RBCs treated with trypsin (180,000 U/ml), but did react with his α-chymotrypsin-treated RBCs. Amplification and sequencing of DNA from the father revealed a single point mutation, 204C → T, in GYPA exon 3. At birth, the baby had clinical symptoms of HDN and was transfused with 36 ml of packed RBCs and received phototherapy for eight days. At week 11, the baby’s M+N+S+s+Or+ RBCs were negative on the DAT. Conclusion: This is the first case of HDN caused by anti-Or. The observed point mutation, 204C → T, confirms that of a previous report and predicts a change of Arg (Or–) to Trp (Or+) at amino acid 31.

The Pig as an Experimental Model for Elucidating the Mechanisms Governing Dietary Influence on Mineral Absorption

“…While externally there are many obvious morphological differences between humans and pigs, their internal anatomy and physiology is very similar (1,14,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Table 1 (27,(41)(42)(43)(44)(45)(46)(47)(48)(49) provides a comparison of some biochemical and physical aspects of pigs and humans. For nutritional studies, the digestive system and its accompanying metabolic processes are the focus of concern when selecting an appropriate experimental research model.…”

“…The most apparent macroscopic difference between the human and porcine intestine is their lengths. The small intestine of adult pigs is around 15-22 meters, while the large intestine has an average length of 4-6 meters (Table 1) (27,(41)(42)(43)(44)(45)(46)(47)(48). In contrast, the small intestine of a human adult averages around 5.5-7 meters, while the large intestine is around 1.5 meters (26,44,(50)(51).…”

Low-incidence MNS antigens associated with single amino acid changes and their susceptibility to enzyme treatment

“…The Or antigen has tryptophan, instead of arginine, at amino acid residue 31, 9,10 which ablates one of the trypsin cleavage sites. Thus, depending on the extent of trypsin treatment of antigen-positive RBCs, the Or antigen may be sensitive or weakened.…”