Kyoichi Kano

Tubular Lesions Produced by Autoantibodies to Tubular Basement Membrane in Human Renal Allografts

In two patients with chronic glomerulonephritis who received renal allografts, transplant failure was associated with binding of transplantation antibodies to the graft and with glomerular and vascula

CYTOTOXICITY OF HUMAN THYROID AUTOANTIBODIES

The knowledge that damage of living tissue cells can occur by way of an immunological mechanism has intensified interest in reactions between antigens of living cells and their corresponding antibodies. T o evaluate the cytotoxic effect of serum autoantibodies, we have employed the techniques of cell culture. In recent years, the cultivation of thyroid cells by Pulvertaft et al. and the use of such cells for evaluating the cytotoxic effect of thyroid autoantibodies has been reported by Pulvertaft, Doniach, Roitt and Hudson,, Irvine,, Forbes et al. and Chandler et al. It is the purpose of this paper to review our own findings in this area and to present some additional approaches to the problem, We obtained a selection of human thyroid tissue and serum from patients undergoing surgery for various disorders of the thyroid. The thyroid tissue was minced and treated with a mixture of 0.1 per cent collagenase and 0.06 per cent trypsin to obtain a dispersed cell suspension.. We have demonstrated that these cells will grow in culture as epithelial-like cells, and for a short time a t least will retain the ability to take up radioactively labeled iodine and to maintain a cytoplasmic organ-specific antigen which can be detected by immunofluorescense. I n the intact thyroid tissue, this antigen is found only in the cells lining the follicles.

Detection of circulating immune complexes by the inhibition of anti-antibody.

Abstract An inhibition test of agglutination of sensitized erythrocytes by human or rabbit anti-antibody was established for the detection of circulating immune complexes. Anti-antibody is a previously described IgM serum factor which combined specifically with homologous IgG antibodies that underwent molecular transformation in reaction with their corresponding antigen. In testing in vitro -formed immune complexes by human or rabbit IgG antibodies, it was found that this test is capable of detecting immune complexes at antigen concentration as low as 2–3 μg/ml. After the addition of corresponding antigens, all 14 serum-sickness sera and all 9 chronic thyroiditis sera which contained precipitating antibodies inhibited human anti-antibody. IgG of normal human sera, heataggregated IgG, and repeatedly frozen and thawed normal sera gave negative inhibition tests. By means of this inhibition test, immune complexes were demonstrated in 35% of the systemic lupus erythematosus sera, 69% of the rheumatoid arthritis sera, 54% of the malaria sera, 22% of the postrenal transplantation sera, 22% of the liver disease sera, 32% of the leukemia sera, and 35% of the lymphoma sera. All 19 of the leprosy sera from India also gave positive results. None of the sera of 36 healthy staff members and only 3% of the sera of random blood donors gave positive results.

Immunologic sequelae of thermal injury.

1) Thermal injury induces a marked inhibition in the ability of tuberculin‐sensitive guinea pigs to respond to intradermal challenge with tuberculin. The effect is most marked during the first and second weeks after burning, but may persist as long as five weeks.

Mixed Agglutination with Platelets

Platelet layers firmly adhering to the glass surface were obtained by allowing human platelets to sediment onto the wall of test tubes or onto glass slides and ‘fixing’ them by means of a 2% formaldehyde solution. Mixed agglutination tests with these platelet preparations were performed in following the procedure used for studies on monolayer cell cultures. It was shown that platelets contain human species-specific antigens similar to those present on all human nucleated cells. Reactions with human sera containing antibodies to alloantigens were also studied. Mixed agglutination tests with platelets gave antiserum titers 100 times higher than those obtained in the corresponding lymphocytotoxicity tests. In some instances, mixed agglutination tests with platelets detected HL-A antigens which were not demonstrable by means of lymphocytotoxicity tests.

Classification of Human Heterophile Antibodies

A classification of heterophile antibodies is proposed, which is based on interactions with guinea pig kidney homogenate. The major groups of antibodies combining with guinea pig kidney encompass Hanganutziu-Deicher antibodies, Forssman antibodies, and antibodies to Newcastle disease virus. Antibodies which fail to combine with guinea pig kidney are primarily those of Paul-Bunnell variety.

Immune complex disease.

Immune complex (IC) disease can be defined as a pathologic condition resulting from the deposition of circulating IC in various tissues or the in situ formation of IC within an organ. In the middle of the last century, Claude Bernard [ l ] noted that injections of sera from foreign species would result in proteinuria. Following the establishment and wide application of therapy with antitoxic sera, a number of symptoms resulting from the injection of serum from a foreign species into human beings were noted. The most frequently observed symptoms were fever, urticaria, joint pain and swelling of lymph nodes; in rare instances, sudden death was observed. In 1905, VOR Pirquet and Schick [2] reviewed a number of such patients and coined the term ‘serum sickness’ to denote the symptoms induced by injections of serum from foreign species. Other investigators [3,4] noted a marked leukopenia and a decrease

Antibody-Induced Lysis of Nucleated Cells in Agar Gel

Cytolysis of nucleated cells incorporated into agar gel was studied using hetero- and isoantibodies. Evidence was presented that IgG and IgM antibodies may participate in these reactions. Studies on t

Hemagglutinins in Sera of Africans of Gambia

Summary Thirty-eight sera from Africans of Gambia were studied serologically. Twenty-two sera had increased titers of agglutinins to guinea pig erythrocytes and 20 had increased titers of rat hemagglutinins. Of 19 individuals of blood group O, 9 had increased titers of agglutinins to human A and/or B erythrocytes. Eleven of 38 sera agglutinated human blood group O erythrocytes exposed to trypsin. Possible relation of these serological findings to infectious processes, especially malaria, is discussed.

Comparison of various procedures for the detection of antigen-antibody complexes.

The described test of inhibition of AA activity proved to be a procedure of exquisite sensitivity and specificity for detection of immune complexes. This could have been expected since AA is an antibody specifically combining with IgG antibody that suffered molecular transformation in the reaction with its corresponding antigen. Complexes formed at or close to the equivalence zone were most active in inhibiting AA, whereas those at extreme antigen excess did not inhibit it at all. Inhibition of AA was capable of detecting circulating immune complexes as well as immune complexes deposited in the tissues. It was also shown that by using this procedure, identification of the antigen participating in immune complex formation is feasible since excess of the specific antigen converts inhibitory complexes into inactive complexes.