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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.

In a Canadian family of northern Irish origin, a new hemoglobin variant, hemoglobin Etobicoke, was observed. It differs from hemoglobin A by having a residue of arginine in place of serine in position 84 of the α-chain (helical notation F5). This hemoglobin is slightly less stable than hemoglobin A, but it does not cause an inclusion body anemia.

Two cases of chronic granulocytic leukemia were considered atypical because abnormal “monocytoid” granulocytes and morphological abnormalities of the erythrocytes were present. This suspicion was confirmed by the course of the disease and by the existence of several abnormal chromosome cell lines in both patients, including double Ph1 chromosomes. The presence of Ph1 chromosomes suggested the patients were in a “preblastic” stage of chronic granulocytic leukemia, particularly since double Ph1 chromosomes have been reported in the terminal stages of other cases of this type of leukemia.

Summary. In one type of hereditary dyserythropoietic anaemia, HEMPAS (hereditary erythroblastic multinuclearity with a positive acidified-serum test) striking increases in the activity of some, but not all, erythrocyte enzymes have been detected in three cases. Since there was only minimal reticulocytosis, these enzyme changes cannot be accounted for by the presence of a young erythrocyte population. It is suggested that the enzymatic abnormalities of HEMPAS result from abnormal karyo- and cyto-kinesis of the erythroid precursors.

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.

In a Canadian family of British origin, a new hemoglobin variant, hemoglobin Manitoba, was observed. It was shown to differ from hemoglobin A by having a residue of arginine in place of serine in position 102 of the α-chain (helical notation G9). There was no evidence that this hemoglobin variant has any adverse clinical symptoms.

SUMMARY Hyperacute rejection of cardiac allografts was studied in dogs sensitized by two previous heart, kidney, or skin grafts or more. Organ donors were selected on the basis of a positive cytotoxicity test using the donor's lymphocytes and the recipient's serum. Eight of the 19 heart grafts were rejected in less than 4 hr; 7 of the 8 were rejected in less than 1 hr. Characteristic gross changes included cyanosis and turgor. Serial biopsies of myocardium within the first 1/2 hr showed interstitial edema and hemorrhage, but no infiltration with inflammatory cells. Small arterioles and capillaries were occluded by clumps of platelets. In most hearts, immunofluorescence staining revealed IgG in the walls of blood vessels and on the sarcolemma. Bound complement (β10-globulin) was seldom detected. There was some correlation between the occurrence of hyperacute rejection and the titer of cytotoxic antibody in the recipient's serum against the donor's lymphocytes. It is suggested that antibody-antigen complexes formed in the graft cause platelet aggregation with occlusion of the lumen and damage to the walls of small blood vessels.

Blood chimaerism in twins of unlike sex was established by karyotypes and by differences in five genetic marker systems. The female twin produced an unusual antibody (anti-A 1 Le b ) which agglutinated the A 1 red blood-cells in the male twin's blood. This apparent breakdown of immune tolerance could be explained by the postnatal development of Lewis substances, and the consequent lack of molecules with A 1 Le b specificity in the plasma of the group-A fetal blood grafted from the male to the female twin in utero. This graft contained only blood-cells, and not secretory cells: thus, although 50% of the female twin's red blood-cells were A 1 ,Le(b+), she could not secrete A and A 1 Le b substances into her body fluids. Transformation experiments, in vitro and in vivo, supported the new hypothesis that the plasma of A 1 ,Le(b+) subjects normally contains A 1 Le b molecules.

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.

Cardiac rejection was studied in 25 mongrel dogs receiving heterotopic abdominal cardiac allografts from unrelated donors. Seventeen recipients were not given immunosuppressive therapy; the other eight were treated with antilymphocyte serum. Antibodies cytotoxic to dog lymphocytes were detected in the serum of five dogs after transplantation. Immunofluorescence studies showed the presence of IgG deposits on the sarcolemma of hearts undergoing rejection. In addition, there were focal IgG deposits on many of the recipients' own hearts, including five which showed changes of focal myocarditis when stained with hematoxylin and eosin. In the dogs treated with antilymphocyte serum, rejection was delayed, and the histological changes were modified. However, the development of lymphocytotoxic antibody and the deposition of IgG were unaffected.

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.