Coombs-positive Hemolytic Anemia Research Articles

Insulin resistance in juvenile diabetes mellitus: Immunologic studies

A case of insulin-resistant juvenile diabetes mellitus with lymphadenopathy, hepatosplenomegaly and Coombs-positive hemolytic anemia is presented. Anti-insulin—containing plasma cells were recovered from the child's bone marrow, and he was found to have a poor humoral and cellular immune response to antigens other than insulin. The patient's erythrocytes were shown to be coated with a monoclonal, IgG, anti-insulin antibody, and this was found to be antigenically, electrophoretically, genetically and immunochemically identical with the serum mediated anti-insulin antibody. The child's serum was found to contain more insulin-anti-insulin soluble immune complexes than free anti-insulin antibodies, and it is suggested that these complexes coated the erythrocytes and rendered them Coombs-positive. The immunopathology of this syndrome is discussed in relation to immune complex disease.

Immunologic Reactions to Penicillin and Cephalosporin Drugs.

Meeting Abstracts1 May 1970Immunologic Reactions to Penicillin and Cephalosporin Drugs.Lawrence D. Petz, M.D., F.A.C.P., Lee Wilkinson, M.D., Peter Spath, M.D.Lawrence D. Petz, M.D., F.A.C.P.Search for more papers by this author, Lee Wilkinson, M.D.Search for more papers by this author, Peter Spath, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-812_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of the present study was to investigate the incidence and clinical significance of immunologic reactions to cephalosporins and penicillins. Previous reports have documented that Coombs-positive hemolytic anemia may be caused by the administration of penicillin in high doses and that significant in vitro cross-allergenicity occurs between penicillin and cephalothin in humans. Reports from other laboratories have indicated that 38 to 75% of patients receiving cephalothin develop a positive direct Coombs' test and that allergic reactions may occur on the basis of cross-allergenicity between the drugs. Our present study concerns immunologic testing in 110 patients receiving penicillins or cephalosporins.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, Calif. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIncidenz und Mechanismus des positiven direkten Antiglobulin-(Coombs-)Testes bei Cephalosporin-Behandlung 1 May 1970Volume 72, Issue 5Page: 812-812KeywordsAllergy and immunologyClinical immunologyDrugsHemolytic anemiaPatientsPenicillin Issue Published: 1 May 1970 PDF downloadLoading ...

Coombs-positive drug-induced hemolytic anemia.

Two cases of Coombs-positive drug-induced hemolytic anemia are presented. One case was associated with the prolonged administration of methyldopa (Aldomet). An antibody which reacted like the antibodies found in autoimmune hemolytic anemia was present in the patient's serum and eluted from the Coombs-positive erythrocytes. The drug was not necesssary in the test system to produce a positive antiglobulin reaction. The second patient's blood contained a circulating antibody that was drugdependent (penicillin). Both patients reached essentially normal hematologic levels after discontinuation of the offending drugs.

Erythrocyte Autoantibody Associated with Alpha-Methyldopa: Heterogeneity of Structure and Specificity

Abstract A case of Coombs-positive hemolytic anemia associated with alpha-methyldopa therapy was studied with particular attention to the structure and specificity of the erythrocyte autoantibodies. Eluted auotantibodies were found to be heterogeneous in both respects. Serologic evidence was obtained for the presence of at least four antibody specificities, all possibly related to the Rh complex: "anti-e," "anti-c," and at least two additional specificities for undefined antigens which may be a part of the hypothetic Rh "core" or precursor substance. The autoantibody population was found to contain γG globulins with both κ and λ light chains and three heavy-chain subclasses, in proportions approximating those found in normal human serum. These findings are judged to be most compatible with a response of basically normal lymphoid tissue to some antigenic alteration brought about by alpha-methyldopa or a derivative.

Effects of neonatal thymectomy on spontaneous murine autoimmune disease.

SummaryThymectomies were done on the first day of life in NZB-NZW and NZB-NZC F1 hybrid mice. Sham thymectomized and nonthymectomized animals served as controls. Survival was somewhat shortened in thymectomized animals. The appearance of antinuclear antibodies, but not of Coombs positive hemolytic anemia was accelerated. There was little effect of thymectomy on the morphology of spleen and lymph nodes. When considered in relation to recent work on the bursa of Fabricius the results suggest that the mammalian analog of the bursa, rather than the thymus, may play a more important role in the pathogenesis of the murine autoimmune disease.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN CHILDHOOD AND ADOLESCENCE

Two cases of PNH in adolescence and childhood are reported. The first presented at age 7½ years with aplastic anemia and improved after splenectomy performed at age 14. The second, a 15-year-old girl, presented with a Coombs-positive hemolytic anemia and has had a course complicated by multiple peripheral thromboses. The clinical and laboratory manifestations, complications, and certain therapeutic aspects of PNH are discussed. Anticoagulant therapy appears indicated in the presence of multiple thrombotic episodes. Erythrocyte metabolic studies revealed normal glycolysis, ATP stability, and GSH content in the cells of a child with a normal reticulocyte count. Mild elevations of glycolysis, noted in the child with a reticulocytosis, was ascribed to a younger mean red cell population since further elevations found in the "top" reticulocyte-rich layer after centrifugation. Heparin, the anticoagulant used in these studies, had no adverse effect on glycolysis but did inhibit hemolysis and minimize ATP instability when compared to cells suspended in defibrinated serum. Erythrocytes fractionated by centrifugation revealed increased glycolytic enzyme activities of hexokinase, G3PD, PGK, TPI, PK, LDH, G6PD, and 6PGD in the reticulocyte-rich layer. Normal, rather than increased activity of aldolase, a membrane enzyme, may reflect damage to the red cell membrane. PFK, known to be decreased in the erythrocyte of neonates, showed normal activity, but it was lowest in the reticulocyte-rich layer. Fetal hemoglobin was elevated in this layer. AChE deficiency and increased suceptibility to hydrogen perioxide and acid hemolysis confirmed previous reports and were most marked in the young cell layer. The level of increased glycolytic rates and enzyme activity, AChE deficiency, acid hemolysis and peroxide hemolysis were related to the clinical severity of the disease.

Coombs-Positive Hemolytic Anemia Caused by Penicillin Administration

CIRCULATING antipenicillin antibody (CAPA) was first reported by Ley et al.1 During routine blood-banking procedures the serum of a prospective transfusion recipient was found to agglutinate an entire panel of erythrocytes that had been stored with penicillin as part of the preservative; erythrocytes from the same donors, when not exposed to penicillin, were not agglutinated by this serum. Ley and his co-workers1 and Watson, Joubert and Bennett,2 in tests on 2000 and 3000 unselected serums, respectively, found this antibody only in donors who had previously received penicillin. Although there is an increased incidence of the antibody in allergic persons3 4 5 6 7 8 it . . .

AUTOIMMUNE DISEASE IN NZB/BL MICE. I. PATHOLOGY AND PATHOGENESIS OF A MODEL SYSTEM OF SPONTANEOUS GLOMERULONEPHRITIS.

This study, based upon 528 laboratory examinations and 16 complete autopsies of NZB/Bl mice, deals with autoimmune manifestations (as shown by hypergammaglobulinemia, Coombs positive hemolytic anemia, and the occasional presence of lupus- and rheumatoid-like factors) and mainly with the pathology and the pathogenesis of glomerulonephritis in these mice, a model system of membranous glomerulonephritis with spontaneous and insidious onset, progression through chronic stages, and almost certainly induced by immunological, and autoimmune, mechanisms. The earliest and lasting histological change was hyaline thickening of the capillary walls and adjacent intercapillary regions of the glomerular tufts, corresponding in location to polysaccharide-rich capillary basement membrane and mesangial materials. Distributed focally and diffusely in the glomerular tuft and eventually sparing no glomerulus, hyaline, granular, and fibrillar ("spongy fiber") materials produced narrowing of capillary lumens by concentric or eccentric encroachment upon them. In the later stages hyaline lobulation and sclerosis of the glomerular tufts occurred. Thus the lesions corresponded to those seen in human focal and diffuse membranous, chronic lobular, and lastly (intracapillary) sclerosing glomerulonephritis. In all instances of glomerulonephritis the glomerular tufts contained selective localizations of mouse immunoglobulins corresponding in distribution to that of the hyaline and (PAS-positive) polysaccharide-rich materials in the focal and diffuse membranous and lobular lesions and in amounts increasing with the severity of glomerular disease. The mouse immunoglobulins were extracted from frozen sections of glomerulonephritic kidneys and were then capable of recombination with glomerular tufts in sections of autologous or isologous glomerulonephritic kidneys from which in vivo localized immunoglobulins had been extracted. The pattern of recombination with glomerular tufts was similar to that of in invo localized immunoglobulins. The extracted immunoglobulins did not show affinity for mouse red cells (in the indirect Coombs test) nor for autologous or isologous cell nuclei (in the immunofluorescence test). The serum of mice with severe glomerulonephritis contained immunoglobulins with in vitro affinity for extracted autologous or isologous glomerular tufts. Thus circulating as well as localized antibodies were demonstrated. The immunogenic materials (autoantigens) may have been formed in the glomerular tufts or accumulated in them from some other source, such as the circulating plasma; however they corresponded in location to polysaccharide-rich capillary basement membrane and mesangial materials. The spleen was identified at the cellular level as the main site of formation of autoantibodies to red cells, as well as the main site of red cell destruction. Some evidence was brought forth suggesting that these autoantibodies were "heavy" or gammaM-globulins. More studies are in progress.

COOMBS-POSITIVE HEMOLYTIC ANEMIA AND GENERALIZED AMYLOIDOSIS IN MICE FOLLOWING TRANSMISSION OF SUBCELLULAR LEUKEMIC MATERIAL.

SummaryFollowing transmission with cell-free supernatant fluid or with virus extract of leukemic tissue or plasma from various types of murine plasma cell leukemias a disease developed, characterized by hyper-gammaglobulinemia, weight loss, anemia, marked splenic, renal and hepatic amyloidosis and plasma cell infiltrations in the lungs. The disease was also transmissible through the placenta or with the milk of infected mice. In DBA/2 males the incidence of the disease was much higher (100%), the survival shorter and the anemia much more severe than was the case in DBA/2 females and in (DBA/2 × CBA) Fimice of both sexes. It is proposed that the development of the lesions is mediated through an autoimmune mechanism created by the antigenic effect of the virus-transformed host cells.Addendum: Dmochowski (Symposium on Current Research in Leukaemia, Cambridge Univ. Press, in press) has reported on the presence of Mycoplasma (PPLO) in the blood of leukaemic mice and in the blood of leukaemic patients, in addit...

THE CROSS-REACTIVITY OF LYMPHOCYTE AND RED CELL ANTIBODIES.

Abstract This study, stimulated by the observation that in chronic lymphocytic leukemia both lymphocytes and red cells may be coated with antibody globulins reactive with Coombs antiserum, defined the presence of common red cell and lymphocyte cellular antigens by demonstrating that their experimentally induced antibodies are cross-reactive. This was done by immunizing rabbits with separate antigens and, with appropriate agglutinations and absorptions, quantitating homologous (concordant) and heterologous (discordant) antibody reactivities. Finer details of these antibodies were delineated by sensitizing lymphocytes with matched and mismatched antisera, subsequently incubating them with red cells, and evaluating these reactants for mixed lymphocyte-red cell agglutination and separate red cell clumping. In addition, dissociation of nonagglutinating lymphocyte antibody from the lymphocyte and reassociation on the red cell were tested by the mixed agglutination technique in combination with rat anti-rabbit globulin. The composite findings suggested that both cellular elements share antigens with like structural groupings but that lymphocyte antibody has a greater avidity for the red cell than red cell antibody has for the lymphocyte. This experimental antibody partitioning, also observed clinically, suggests that the lymphocyte may be coated prior to the red cell in the Coombs-positive hemolytic anemia of chronic lymphocytic leukemia and that the current autoantibody concept of this type of anemia might be reappraised on this account.

Lilly Lecture: The Thymus and Auto-immune Disease.

Excerpt The lecture is based primarily on the finding A that a strain of mice, NZB, which spontaneously shows 3 classical manifestations of autoimmune disease, Coombs positive hemolytic anemia, a h...