Biomedical subjects
Publications and source records attributed to J Wingham.
A patient with myelofibrosis was studied for about four years. During this period he developed autoimmune haemolytic anaemia, a rare complication of myelofibrosis. Furthermore, about two years after the investigation started, his red blood cells, previously normal, became Tn-polyagglutinable, a change known to be due to somatic mutation in haemopoietic stem cells.
Extracts of Caiophora coronata or Loasa vulcanica seeds contain a strong lectin for T, Tn, Cad 1, and papain-treated erythrocytes.
2 patients on the drug azapropazone developed positive antiglobulin tests. Their sera were each found to contain two distinct antibodies. One was an IgG antibody, probably a drug-dependent autoantibody of the alpha-methyldopa type, but could have been related to the disease. The other was certainly a drug-dependent antibody of the penicillin type.
The seeds of Medicago disciformis and Medicago turbinata contain lectins for T or Th but not Tk or Tx red cell cryptantigens. Extracts of Medicago disciformis seeds are a useful addition to a panel of lectins used in the classification of red cell cryptantigens and of red cell polyagglutinability.
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A fourth human blood group chimaera studies in Birmingham is an example of haemopoietic (twin) chimaerism in which the subject was unaware of being a twin. Chimaerism was discovered during routine antenatal serological investigation in which it was shown that the proposita has two red cell populations, one of the rhesus genotype rr, and the other R1r. Further studies showed that she has two populations of lymphocytes, one with the female karyotype, 46XX, and the other with the male karyotype, 46XY. Skin fibroblasts were all 46XX.
Red blood cells become polyagglutinable when the normally latent T-antigens of the red blood cell membrane are exposed. Unmasking of T-antigens results from removal of N-acetyl-neuraminic acid by neuraminidase, an enzyme commonly produced by a variety of bacteria. Red blood cells altered in this way are said to be T-activated. T-activated red blood cells can be agglutinated by anti-T, an antibody normally present in human serum, so that severe transfusion reactions may occur and have occurred, if T-antigen positive patients are transfused with normal whole blood or plasma. This can be avoided by transfusing only packed or washed red blood cells. From October 1978 to October 1980 we found T-activation in 16 pediatric surgical patients aged 3 days to 14 yr with severe anaerobic infections. This included patients with necrotizing enterocolitis, perforated appendicitis, megacolon, infected anal atresia and gas gangrene. The isolate neuraminidase-producing bacteria were Clostridium perfringens and Bacteroides fragilis. Clinical data of these 16 patients are briefly reviewed and the importance of T-antigen positivity for their management is discussed.
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The red cells of a normal male blood donor, K.S., were first grouped as B but he was found to lack anti-A in his serum. Closer investigation revealed that his red cells had very weak A activity, demonstrable only by absorption and elution of anti-A. He is a non-secretor of ABH and a secretor of Lea. Blood group A-, B and H-gene specified glycosyltransferases were detected in his serum. In contrast to the finding of a B antigen of normal strength on his red cells, the B transferase in his serum was only about 30% of the normal level and, despite the very weak A activity of K.S's red cells, the A transferase level was about 50% of that found in the serum of group A individuals with normal strength of A antigen. Moreover, the A transferase on the basis of its pH optimum, Km values for donor and acceptor substrates, activation by divalent cations, isoelectric focusing profile and capacity to convert O to A-active cells, was characterized as the product of an A1 gene. A family study showed that K.S's wife is group A2 and that they have two sons, one group A2 and the other group B. The group B son is assumed to have inherited a B gene from the propositus but the level of B transferase in the son's serum is three times as high as that in his father's serum. The wife of the propositus and his group A2 son have normal A2 transferases in keeping with their A2 red cell status. The A2 son therefore appears to have inherited an A2 gene from his mother but neither the A1 nor the B gene shown to be carried by his father. The distribution of transferase activities in K.S's red cells differs from that in his serum. A level of B transferase within the normal range was found in his red cell membranes but a very low level of A transferase was detected. The discrepancies between the serum transferases and ABO red cell group, together with the pattern of inheritance within the family, led to a suspicion of chimaerism. This was confirmed by the finding of fibroblasts with the female 46XX karyotype in cultures of the propositus' skin. These results suggest that K.S. is a dispermic chimaera with two different cell lines of the genotypes BO and A1O or A1A1. The group A2 son is assumed to have inherited an O gene from his father. It seems probable that K.S.'s bone marrow and reproductive organs are comprised predominantly of the XY cell line which carried the blood group BO genotype whereas his skin and other tissues which contribute the A1 transferase to his plasma, are partly made up of the XX cell line which carries the blood group A1O or A1A1 genotype.
Extracts of the seeds of Vicia cretica (NO Leguminosae) strongly agglutinate T- Th- but not Tk- or other polyagglutinable red cells. The V. cretica lectin is therefore a very useful laboratory reagent in the elucidation of erythrocyte polyagglutination due to T-like erythrocyte cryptantigens.
Another example of haemopoietic chimaerism in dizygotic twins is described. Each twin had two distinct blood cell populations. The red cell populations differed in three blood group systems and in other genetic characters, and the white cell population in HLA types and in XX/XY karyotypes. The biological significance of these findings is discussed with special reference to the relative proportions of the two red and white cell populations, the ABH blood group gene-specified glycosyltransferase levels, and the HLA types.
Three seed sources of lectins which are of potential value in the classification of red cell polyagglutinability are described.
A blood group A1 patient on renal dialysis developed transient low-titre, high-avidity anti-A autoantibodies and concurrently a gross depression of the A antigen. The antibodies were clearly anti-A and had no association with I, i or N antigens. They reacted in saline, papain and antiglobulin systems but were inactivated by albumin. Their pathogenesis is obscure.
In 9 out of 26 newborns with necrotising enterocolitis (NEC) exposure of the Thomsen-cryptantigen (T-antigen), probably due to the action of circulating bacterial neuraminidase, was demonstrated on red blood cells. The serological titres seemed to correlate with the clinical course of the disease. Neuraminidase-producing clostridia were isolated in two of the patients. Reaction between the exposed T-antigen and anti-T-agglutinins, normally present in human blood, may lead to difficulties during blood transfusion. This potential transfusion hazard is best avoided by routine T-antigen-tests and by transfusion of packed or washed red blood cells to T-antigen-positive patients.
A predominantly Cad-specific lectin is present in the seeds of Leonurus cardiaca. Extracts of these seeds makes a valuable addition to reagents used in the elucidation of red cell polyagglutinability.
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