Haemolytic disease of the newborn (HDN) is caused by maternal immunoglobulin (Ig) G acting against antigens expressed on mature fetal red cells. Anti‐M antibodies active at 37°C are a rare cause of HDN.1 We report data, arising from the investigation of a neonate with severe transient pure red‐cell aplasia, indicating that anti‐M can cause hypoplastic HDN by inhibition of erythroid precursor growth, as frequently occurs with anti‐Kell antibodies.2
A female neonate presented at 4 weeks of age with severe hypoplastic anaemia (haemoglobin 3.7 g/dl, reticulocytes 11×109/l) and mild jaundice (bilirubin 30 μmol/l). Direct anti‐globulin test was negative. A bone marrow aspirate showed reduced but morphologically normal erythroid precursors. The patient was transfused twice before spontaneous increases in reticulocyte and haemoglobin values were noted at 74 days of age, the haemoglobin value reaching and remaining within normal limits until discharge from follow‐up at 15 months.
The patient's blood group was O M+N+ and that of her mother A M−N+. At presentation, maternal serum contained anti‐M with both IgM and IgG components.
In view of this finding, experiments were carried out to determine the role of anti‐M in causing anaemia. With local research ethics committee approval and parental consent, marrow mononuclear cells from the patient and group O controls (ie, children with acute lymphoblastic anaemia in remission, where excess sample was available at a scheduled marrow examination) were cultured by standard assay (Methocult System, Stem Cell Technologies, Vancouver, Canada) and in the presence of inert serum (from the child's father) and dilutions of maternal serum. On the basis of 95% ranges derived from repeated analysis of two samples (data not shown), reductions in erythroid colony numbers (burst‐forming and colony‐forming units–erythroid combined) in the patient and in controls 2 and 3 with 10% and control 3 with 1% maternal serum were considered significant. No inhibition was seen in a patient with the NN phenotype (table 1). In experiments with absorbed maternal serum, the considerable inhibition of erythroid growth was abolished in one of two samples by prior absorption with group OM+N− cells but not by OM−N+ cells (data not shown).
Table 1 Erythroid precursor colony numbers (per 5×104 nucleated cells) in patient and control bone marrow samples and the effects of both neutral serum and maternal serum (containing anti‐M) at two dilutions.
| Subject | Type | Standard assay | +10% inert serum | +10% maternal serum | +1% maternal serum |
|---|---|---|---|---|---|
| Patient | MN | 39 | 43 | 10 (−74) | NT |
| Control 1 | MN | 46 | 44 | 30 (−35) | 44 |
| Control 2 | MN | 49 | 40 | 21 (−57) | 36 (−27) |
| Control 3 | MM | 63 | 73 | 32 (−49) | 43 (−32) |
| Control 4 | NN | 21 | 20 | 26 (+24) | 31 (+48) |
NT, not tested.
Figures in brackets indicate the percentage change from the value obtained with the standard assay, where this was >20%.
The M antigen is expressed on immature erythroid precursors3 and it is plausible that precursor cell growth would be inhibited by anti‐M. Our patient's clinical picture and our in vitro data provide strong circumstantial evidence that anti‐M should join anti‐Kell as a cause of reticulocytopenic HDN.
Footnotes
Competing interests: None declared.
References
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