Margaret E. Nichols

Chronic Granulomatous Disease and the Kell Blood Groups

Summary. Fifteen antigenic determinants are known to be related to the Kell blood group. Some boys with X‐linked chronic granulomatous disease have the very rare McLeod or K0 phenotype on their red cells. Serological studies of the McLeod type suggest that the weak Kell antigens that are present differ qualitatively and quantitatively from those on red cells of common Kell type. A new antigen, Kx, has been characterized and shown to be present on red cells and neutrophil leucocytes. Lack of red‐cell Kx is associated with the McLeod phenotype, lack of leucocyte Kx is associated with chronic granulomatous disease.

Inhibition of anti-I sera by human milk.

Summary. Human milk has been found to contain a high concentration of water‐soluble I blood‐group substance. Tests with 24 different anti‐I sera showed that to a variable extent all of them could be inhibited by milk and some could be inhibited by strong I secretor saliva. The susceptibility of I antibodies to inhibition was not related to titer, and the results suggest that qualitative differences in the antibody‐antigen reaction are responsible.

The definition of two I antigen components.

Abstract. The I blood group antigen has two main components named IFetal (IF) and IDeveloped (Id). The IF component is present on all human red cells including those of icord and iadult persons, and also on Rhesus monkey red cells. The ID component develops slowly on the red cells before birth and to a greater extent in the 18 months after birth. Inhibition studies with human milk show that strongly‐inhibitable anti‐I sera are of the anti‐ID variety, but only a minority of such sera are inhibitable. Comparative studies on the red cells of 12 newborn infants suggest that the same sequence of I antigen development occurs in them all, but different infants vary in the amount of I development that they have achieved at the time of birth. I antigen variants affect mainly the ID component, and it is this part of the antigen that may be weakened on the red cells of people with leukemia.

Kx antigen, the McLeod phenotype, and chronic granulomatous disease: further studies.

Abstract. Leukocytes of nine unrelated boys with X‐linked chronic granulomatous disease lack Kx antigen. In three of these cases, the red cells also lack Kx and have the McLeod phenotype and abnormal morphology. X‐linked chronic granulomatous disease CGD can thus be separated into two types. Type I cases have an antigenic deficiency that is restricted to the phagocytic leukocytes while in type II, the deficiency involves both leukocytes and red cells. Red cells of type II CGD patients have enhanced i antigen activity suggesting that they are under hemopoietic stress. Normal Kx synthesis is directed by an X‐linked gene named X1k. Three rare variants, X2k, X3k, and X4k order the different permutations of leukocyte and red cell Kx antigen production that have been recognized.

Auto‐Anti‐Kpb Associated with Weakened Antigenicity in the Kell Blood Group System: A Second Example

An 84‐year‐old woman with intestinal bleeding had marked reduction of red blood cell antigenicity in the Kell system, and a positive direct antiglobulin test caused by auto‐anti‐Kpb. Kx antigen activity of her cells was increased, an observation which supports the belief that Kx marks a precursor structure utilized in the normal Kell biosynthetic pathway. It is postulated that reduced Kell antigenicity was an acquired change that resulted from enzymatic degradation, possibly of bacterial origin.

Two blood group M epitopes disclosed by monoclonal antibodies.

Abstract. Two cloned mouse hybridomas, designated G8 and E3, produced anti‐M of immunoglobulin classes IgG2b and IgG1, respectively. No discrepancies were observed in testing over 5,000 normal donor blood samples with appropriately diluted G8 and E3 culture supernatant fluids in parallel with rabbit anti‐M and anti‐N typing reagents. The specificity and titer of antibodies produced by G8 and E3 were minimally affected by changes in temperature (37°C, 22°C, 4°C). G8 and E3 showed reduced activity with type MM red cells that had been treated with either neuraminidase or papain, but differences were observed in the susceptibility of the respective epitopes to treatment with neuraminidase. Furthermore, G8 and E3 exhibited different specificities when used to test the red cells of nonhuman primates and erythrocytes of the rare MgMg human blood type. These results indicate the existence of at least two M antigen epitopes.

Kidd Blood-Group Antigens of Leukocytes and Platelets

Neutrophil leukocytes have a strong absorptive capacity for anti‐JkaJkb, made by Jk (a‐b‐) persons, but do not absorb anti‐Jka or anti‐Jka. The Jka Jkb antigen does not appear to be present on lymphocytes or platelets. The results indicate that JkaJkb activity is not a crossreaction between Jka and Jkb, but is a distinct and separable specificity.

Monoclonal Anti‐K14 and Anti‐K2

Abstract. Mouse hybridoma clones have produced monoclonal antibodies directed against the K:14 and K:2 high‐incidence antigens of the Kell blood group system. Two examples of anti‐K14 were isolated, each arising from a separate fusion procedure. All three monoclonal antibodies are of the immunoglobulin class IgGl. Serological activity is consistent with that seen with human antibodies to high‐incidence Kell system antigens, and their epitopes are destroyed, as usual, by 2‐aminoethylisothiuronium bromide treatment. Specificity was further confirmed by adsorption and elution studies. Tests against nonhuman primate red cells demonstrated the expression of K:14 only by the great apes, whereas K:2 was present on all red cells tested. These findings emphasize the usefulness of monoclonal antibodies to elucidate the evolutionary patterns of blood group variants.

Autologous Anti-I and Anti-M Following Liver Transplant

A patient who received a liver transplant subsequently developed autologous anti‐I and anti‐M. The antibodies were demonstrated in the serum and in eluates from the patients red blood cells, and could be separated by cross‐absorption with appropriate red blood cells. The patient received horse antilymphocyte globulin and the possibility could not be excluded that the anti‐M was transferred passively.

Studies of MNSsU Antigen Activity on Leukocytes and Platelets

Leukocytes or platelets from donors of appropriate blood type do not absorb anti‐M, anti‐N, anti‐S, or anti‐s. Leukocytes from U‐positive donors absorb anti‐U, but white blood cells collected from U‐negative donors do not absorb the antibody. Tests with separated platelets, lymphocytes, and neutrophils indicate that U‐antigen is probably restricted to the neutrophils.