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Of 156 families who were HL-A typed and Chido-typed, 15 were found to be suitable for linkage analysis. It was calculated that the odds in favour of linkage of Chido and HL-A are 1,450,000:1. The maximum likelihood estimate of the Chido:1.HL-A recombination fraction is 2½% with 95% confidence limits, obtained graphically, of 0 and 12%; the estimate of the Chido:2.HL-A recombination fraction is 1½%, with limits of 0 and 9%. Among Chido negative subjects, the antigens HL-A12 and W5 occurred more frequently than in a control population.

A and B and A1Leb substances were adsorbed onto red cells exposed to glycosphingolipid fractions prepared from the serum of group A and B and A1,Le(a minus b plus) donors. Group O cells exposed to fractions prepared from the serum of group A or B donors were agglutinated by an IgM cross-reacting antibody present in some group O sera. Cells exposed to fractions from A1,Le(a minus b plus) serum were agglutinated by anti-A1Leb. The amount of A substance in the fractions was related to the A subtype (A1 or A2) and to the Lewis and secretor phenotype of the donor. The uptake of blood-group substances from the lipid fractions was inhibited by the addition of whole serum to the fractions.

Fetal red blood cells were concentrated from mixtures of maternal and fetal cells by differential agglutination with anti-i serum. This method will be useful for prenatal diagnosis of hemoglobinopathies when blood obtained from the fetus is heavily contaminated by maternal cells. The method is practical, except in very rare cases in which the maternal red cells are strongly agglutinated by anti-i.

Reduction of interchain disulfide bonds converted some IgG incomplete antibodies to direct hemagglutinins. This conversion occurred whether antibody was free in solution or bound to the red-cell surface. Reduced antibody permitted to reoxidize in air no longer behaved as a direct agglutinin; reversion to an incomplete antibody did not occur when reoxidation was prevented by S-alkylation. These results suggest that mild reduction of the antibody imparts sufficient freedom to permit bridging between cells and are interpreted as evidence that the interheavy-chain disulfide bonds restrict segmental flexibility within the Fc fragment of IgG.

The specific inhibition of anti-Chido by the plasma (and serum) of Chidopositive subjects (adult and newborn) is the basis for the Chido-substance inhibition test. This test has proved to be a reliable method for detecting Chido-negative donors, and for identifying anti-Chido. Among 639 random donors in Toronto, the plasma of 11 lacked Chido-substance (i.e., 1.7% were Chido-negative). The Chido-antigen in human plasma is thus a useful genetic marker.

Summary Seven cases, in which the presence of a blood group iso-antibody was unsuspected until several days after transfusion, are described. In one case the rapid appearance of multiple antibodies produced signs and symptoms simulating auto-immune haemolytic anaemia. In two of the seven cases, antibodies were detectable in the pre-transfusion serum only when cells containing a double dose of the corresponding antigen were used.

A soluble glycosyltransferase which can trasfer N-acetylgalactosamine from UDP-N-acetylgalactosamine to exogenous acceptors is present in the serum of human subjects with the blood group A gene. The enzyme is in the serum of secretors and non-secretors of group A and AB but is not in the serum of group 0 or B subjects. The activity of serum from A 1 subjects is 5 to 10 times higher than that from A 2 subjects. Activity was lower in two group A 1 pregnant women. There was low activity in the serum of a hematopoietic chimera whose A 1 gene is restricted to her “grafted” blood cells.

SUMMARY Serum from group O volunteers, who had been injected with porcine A blood group substance, was used in lymphocytotoxicity tests. Positive reactions were obtained only with lymphocytes of group A secretors; the strongest reactors were Le(a-b-). The same group O sera reacted with group O lymphocytes which had been exposed to a glycosphingolipid fraction prepared from the plasma of A, Le(a-b-) secretors. These reactions were specifically inhibited by A substance. It is suggested that, unlike the A antigen on red cells, the A antigen detected in lymphocytotoxicity tests is entirely derived from the plasma.

CHIDO (Ch) AND RODGERS (Rg) are blood-group antigens present in plasma and on red cells. Interest in these antigens was stimulated when Ch (ref. 1) and Rg (ref. 2) were found to be genetic markers for the major histocompatibility complex, HLA, and when strong linkage disequilibrium between the Rg-negative phenotype and HLA-A1, B8 homozygosity was noted3. Ch and Rg recently attracted a broad audience when O'Neill et al.4 showed that the Ch and Rg phenotype of plasma was correlated with the electrophoretic polymorphism of human C4, the fourth component of complement, and that C4 purified to homogeneity inhibited anti-Ch and anti-Rg. We have studied the transfer of Ch and Rg from plasma to red cells in conditions in which C4 is transferred. We report here a correlation between the Ch, Rg polymorphism and functional C4, and show that Ch and Rg reside on the C4d fragment of the molecule. We also report that a monkey antiserum to human C4d (ref. 5) is predominantly anti-Ch and anti-Rg.

The level of blood-group A1-specified alpha,3'-N-acetyl-D-galactosaminyl-transferase in the serum of recently-delivered women was found to be appreciably lower than the level of this enzyme in the serum of non-pregnant adults and of newborn infants; a similar but less striking decrease was observed in the levels of the A2-specified alpha,3'-N-acetyl-D-galactosaminyltransferase and the H-specified alpha,2'-L-fucosyltransferase. Although the red cells of newborn infants are known to have relatively few A and H antigen sites, the serum of neonates was found to have a level of A1- and A2-dependent N-acetylgalactosaminyltransferases and H-dependent fucosyltransferase as high as, if not higher than, the serum of non-pregnant adults. This finding is compatible with the fact that the haemopoietic tissue contributes only about 20% of the serum transferase level.

Summary. Abnormalities of the membrane of HEMPAS red cells have been demonstrated by certain serological tests and in freeze-etch electron micrographs. There is also a marked increase in the activity of certain red-cell enzymes. The positive acidified-serum lysis test has proved useful in distinguishing HEMPAS from other kinds of hereditary dyserythropoietic anaemia. The greatly increased reactivity with anti-i (although characteristic of HEMPAS) is a less specific finding, since enhancement of the i antigen is found in other dyserythropoietic anaemias, hereditary and acquired. Although the lysis of HEMPAS cells by acidified serum at first suggested that their membrane defect was similar to that present in PNH, further investigation showed that the mechanism of activation of complement is different in the two conditions. Lysis of HEMPAS cells depends on the binding of complement by a naturally-occurring, cold antibody (“anti-HEMPAS”) specific for an antigen present on HEMPAS cells, but not detectable on PNH or normal cells. Unlike PNH cells, HEMPAS cells are not lysed by complement in the absence of antibody. As judged by tests with anti-I and human complement, PNH cells have a true increase in sensitivity to complement in that the binding of only a small number of complement sequences is sufficient to effect lysis. The increased lysis of HEMPAS cells by anti-I appears to be due to the binding by antibody of many more complement sequences than are bound to PNH or normal cells. With some examples of anti-I, an increased uptake of antibody by HEMPAS cells also contributes to their increased lysis.

Summary. In five patients (including two sisters) an unusual anaemia was characterized by erythroblastic multinuclearity, ineffective erythropoiesis and a positive acidified-serum test. Unlike PNH, the sugar-water test was always negative in these patients. The lysis of their cells by acidified normal sera indicated their abnormal sensitivity to an agglutinating and complement-binding antibody present in some normal subjects. The patients cells gave high agglutination scores with anti-i, and were unusually susceptible to lysis by anti-i and anti-I. The disorder is apparently inherited as an autosomal recessive character.

SEVERAL blood group antigens are more strongly reactive on adult red cells than on the red cells of new-born infants. A notable exception is the antigen i, which is maximally developed at birth and decreases in strength during the first year of life1. The decrease in antigen i is associated with a reciprocal increase in antigen I, which is poorly developed at birth.

HEMPAS or ‘CDA Type II’ is an autosomal recessive form of congenital dyserythropoietic anaemia, characterized by ineffective erythropoiesis. The clinical and haematological features of 39 patients are reviewed. Anaemia and jaundice are characteristic; less than a quarter of the patients are sufficiently anaemic to need repeated transfusions. The spleen is usually moderately to markedly enlarged and the liver is often slightly enlarged. The bone marrow is strikingly abnormal, with many erythroblasts containing two or more nuclei. The circulating red cells show moderate morphological abnormalities; unlike normal cells, they are strongly agglutinated by anti-i, and lysed by anti-i and anti-I. Moreover, the red cells are agglutinated and lysed by an alloantibody present in many normal sera, but they are not lysed in the patient's own serum. It seems possible that an abnormality of the cell membrane may be the cause of the defective cell division, the failure of the multinucleated erythroblasts to expel their nuclei, and the characteristic serological reactions.

USUALLY Ii specificity is assigned to cold agglutinins on the basis of their reactions with the red cells of human adults (adult red cells) and newborn infants (cord red cells). Those which react more strongly with adult red cells are said to detect I antigen and are designated anti-I; those which react more strongly with cord red cells are said to detect i antigen and are designated anti-i1,2. We have now found that I and i antigens can be easily detected on lymphocytes.

The ABO system has two features unique among blood-group systems: the antigens (A, B and H), when present, are widely distributed in the cells and fluids of the body; and the antibodies (anti-A, an...