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Biomedical subjects

P D Issitt

Publications and source records attributed to P D Issitt.

At least 55 records · Page 3Linked to original sources

High frequency antigens of human erythrocyte membrane sialoglycoproteins. I. Ena receptors in the glycosylated domain of the MN sialoglycoprotein.

The specificity of various allo- and autoantibodies, which agglutinate normal erythrocytes, but do not react with En(a-) red cells and normal erythrocytes, treated with trypsin (anti-EnaTS) or ficin (anti-EnaFS), was investigated. Various fragments and modification products of the major (MN) red cell membranes sialoglycoprotein were used in hemagglutination inhibition assays. Six anti-EnaFS sera were found to be directed against the residues approx. 46-56 of the molecule. Five of these require the carbohydrate unit, attached to Thr50, for binding. One anti-EnaTS serum was found to be directed against the residues approx. 36-42. Another antibody with anti-EnaTS specificity was shown to react with the residues 31-39 in some of the MN sialoglycoprotein molecules, namely those not glycosylated at a certain position (probably Thr33). A third anti-EnaTS serum, directed against the sequence domain around Lys30, was also found to react only with a fraction of the molecules, apparently due to the variable attachment of oligosaccharides in that region. The heterogeneity of glycosylation, detected by these two sera, appears to account for the partial tryptic and chymotryptic cleavage in this domain of the MN sialoglycoprotein, which has been described previously. Heterogeneity of the glycosylation at various positions of the molecule could be established by the isolation and analysis of peptides.

Amino Acid Sequence↗

Atypical presentation of acute phase, antibody-induced haemolytic anaemia in an infant.

We describe a case of 'warm' antibody-induced haemolytic anaemia (WAIHA) in which marked depression of red cell Rh antigen expression resulted in the patient presenting with severe anaemia but a negative direct antiglobulin test (DAT). The serum contained potent IgG Rh antibodies. Unlike two previously reported cases (Koscielak, 1980; Veer et al. 1981) in which the diagnosis of WAIHA was established before the DAT became negative, this patient presented with negative serological findings during his first episode of anaemia. As a result, the serum antibodies appeared to be allo- not autoimmune in nature and to be unrelated to the patient's anaemia. Confirmation of the autoimmune nature of the Rh antibodies was not possible until nearly 2 years after the first episode of anaemia.

Anemia, Hemolytic, Autoimmune↗

Critical re-examination of the specificity of auto-anti-Rh antibodies in patients with a positive direct antiglobulin test.

Forty-eight autoantibodies with apparent 'simple' anti-Rh specificity (anti-e, -E, -c, -D, -C, -Ce, -G), have been studied by means of multiple absorption tests. The finding that 34 (70.8%) of these antibodies could bind to red blood cells lacking the antigens that the antibodies appeared to define, indicated that the antibodies had different specificities than seemed to be the case in initial antibody identification tests. Those autoantibodies that at first appeared to be directed against the Rh antigens e, E or c, most often had anti-Hr or anti-Hro specificity. These data explain why some apparent anti-Rh autoantibodies can be eluted from the red blood cells of patients negative for the antigens that the antibodi:s appear to define. However, they also illustrate that the phenomenon of autoantibodies mimicking specificities that they do not possess is common in patients positive for the antigens against which their autoantibodies appear to be directed. An explanation for the mode of action of these autoantibodies in complexing with the Rh agglutinogen is proposed, and the significance of the antibodies in transfusion therapy is considered.

Anemia, Hemolytic, Autoimmune↗

The antigen Duclos. A new high frequency red cell antigen related to Rh and U.

An antibody is described which defines a new high frequency red cell antigen, Duclos, whose expression seems to require the presence of both U and Rh fundamental antigens. Apart from the antibody maker's own red cells the only nonreactive samples were from Rhnull U impaired individuals, one example of which was shown however to yield very slight amounts of antibody through absorption-elution tests. Rhmod U weak cells gave very depressed and Rhnull U positive or Rh common U negative cells moderately depressed reactions. The proposita's red cells had an apparently normal Rh-LW condition but their U antigen was significantly decreased. No further Duclos negative individual was found by screening 8,500 blood donors in the Paris area.

Aged↗

Autoimmune hemolytic anemia and cold hemagglutinin disease: clinical disease and laboratory findings.

As is apparent from the length of this review, a multitude of laboratory investigations can be performed on the blood of patients with AIHA and CHD. Unfortunately, because of the considerable complexity of some of these tests, their significance is not always apparent to the physician who treats the patient. Communication gaps between the laboratory scientist and the physician at the bedside are bound to occur because of the high degree of specialization of both immunohematology and medical care. The purpose of this review has been to bridge the communication gap. The agents that cause AIHA and CHD are antibodies. Although they are often autoantibodies of complex specificity, usually reacting with all normal red cells, they nevertheless obey most of the rules explaining the action of alloantibodies that sometimes complicate transfusion therapy. By approaching AIHA and CHD as antibody-induced conditions, and by regarding autoantibodies as similar in their actions to alloantibodies, hopefully, physicians will appreciate the significance of the tests performed in the laboratory. For their part, the laboratory workers will be able not only to report test results but also to explain the findings. This review may aid in establishing the essential dialogue.

Agglutinins↗

Anti-Wrb, and other autoantibodies responsible for positive direct antiglobulin tests in 150 individuals.

Eluates from the red blood cells (and sera whenever free autoantibody was present) of 150 individuals with positive direct antiglobulin tests, have been studied for antibody specificity. Of 87 patients with AIHA, 64 had autoantibodies reacting with all red cell samples including Rhnu11. Of these 64 anti-d1 autoantibodies, two were, and 32 contained, auto-anti-Wrb. Of 33 patients being treated with alphamethyldopa, who had developed positive direct antiglobulin tests, 23 had anti-d1 autoantibodies four of which contained auto-anti-Wrb. Of 30 haematologically normal donors with positive direct antiglobulin tests, 23 had anti-d1 autoantibodies, two of which were, and six of which contained, auto-anti-Wrb. The full specificities of autoantibodies, other than anti-Wrb and anti-d1, in the 150 patients are described, as are the natures of the protein red cell coatings that caused the positive direct antiglobulin tests. The presence of free serum autoantibody as a correlate of the three clinical conditions is reported. Several observations on auto-anti-Wrb are documented. The antibody can cause gross red cell destruction in vivo, but can be benign on other occasions; it occurs with approximately the same frequency in AIHA patients and "normal" donors with positive direct antiglobulin tests, but in fewer patients with alphamethydopa induced positive direct antiglobulin tests; it does not activate complement in vivo; and finally it may eventually provide a clue to the aetiology of AIHA.

Anemia, Hemolytic, Autoimmune↗