A combination of IgG and IgM autoantibodies in chronic cold agglutinin disease: immunologic studies and response to splenectomy.
ABSTRACT A patient with chronic cold agglutinin disease and anti-I antibody was studied. The titer of the patient's serum at 4 degrees C was 700 with adult I RBC, 256 with cord RBC, 256 with adult i RBC. At room temperature the titers were decreased and the serum also reacted at a titer of 4,000 with enzyme treated adult I RBC. Dithiothreitol treatment of the serum and purified antibody decreased reactivity only slightly, indicating that the antibody was IgG. The heat eluate contained 1.2 mg/ml IgG kappa, but only 80 micrograms/ml IgM kappa. A hybridoma made by fusing the patient's peripheral blood lymphocytes with a human myeloma cell line contained only IgM kappa (30 micrograms/ml) anti-I activity. The IgM fraction of the heat eluate reacted similarly to the hybridoma supernatant. The IgG fraction resembled the serum and heat eluate. In this case study, IgG kappa and IgM kappa immunoglobulins, both possessing cold agglutinin activity, were present in the patient's serum. This finding is unusual in idiopathic cold agglutinin disease and in view of the predominance of an IgG cold agglutinin, splenectomy was recommended for treatment.
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ABSTRACT: A 65-year-old white man had severe hemolytic anemia due to a mixture of low-titer IgG lambda and IgM lambda agglutinins showing optimum reactivity at 22 degrees C. The IgG agglutinins were detected by manual indirect antiglobulin test (IAT) using anti-IgG, and had a titer of 1 at 37 degrees C, 128 at 22 degrees C and 16 at 4 degrees C against adult type O red blood cells (RBC). The corresponding titers with cord RBC were 1 (37 degrees C), 64 (22 degrees C) and 8 (4 degrees C). Proteolytic enzyme and neuraminidase treatment of RBC did not decrease these titers. No known specificity could be assigned to these agglutinins. The isolated agglutinins (recovered by cold adsorption, warm elution) were shown by immunoelectrophoresis to be IgG lambda antibodies. They did not bind complement in vitro, consistent with the finding that the patient had negative manual direct antiglobulin test (DAT) by anti-C3d. It could be shown only by automated IAT that patient's serum also contained IgM cold agglutinins which also reacted best at 22 degrees C and appeared to be of lambda light-chain type. The patient responded to corticosteroid therapy and remains well without treatment 14 months after the hemolytic episode. The presence of IgG cold agglutinins may be predictive of a favorable response to corticosteroid therapy.Vox Sanguinis 02/1986; 51(2):112-6. DOI:10.1111/j.1423-0410.1986.tb00225.x · 3.30 Impact Factor
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ABSTRACT: Monoclonal antibody technology has been used in both murine and human systems to produce a variety of antibodies that react with the human red cell (RBC). RBC monoclonal autoantibodies have been obtained from animal models of autoimmune hemolytic anemia (AIHA), but to date no warm-reactive monoclonal autoantibodies have been generated from human B cells. Using the Epstein-Barr virus (EBV) transformation method, clones of RBC autoantibodies were generated from two patients with AIHA. These antibodies reacted preferentially at 37 degrees C, agglutinated or bound to a variety of different RBC phenotypes, and were IgM in nature. The serologic reactivity of one clone showed a relative specificity to e+ RBCs that was similar to that seen in the patient's serum. These results are the first to demonstrate that warm-reactive RBC autoantibodies can be obtained from patients with AIHA using the technique of EBV transformation, and they further substantiate the existence of warm-reactive IgM RBC autoantibodies in the spectrum of warm AIHA.Transfusion 03/1989; 29(3):196-200. DOI:10.1046/j.1537-2995.1989.29389162722.x · 3.57 Impact Factor
Article: Cold agglutination.[Show abstract] [Hide abstract]
ABSTRACT: Autoantibodies against red cells optimally reacting at 0 degree C, ie, CA, are normally found with low titers in the serum of human adults. High-titer CA may be induced by certain infectious agents, including M pneumoniae, EBV, CMV, and rubella virus, or may develop on the basis of chronic (malignant) B cell lymphoproliferation. The main clinical manifestation of cold agglutination is AIHA. Antigens and antibodies of cold agglutination are the best characterized reaction partners of a human autoimmune process. CA may recognize I and i antigens, which are lipid- and protein-linked branched and linear N-acetyl-lactosamine chains, respectively. They are precursors of the ABH blood group antigens and are converted into H by fucosylation. An alternative substitution by sialylation creates Gd, Fl, and probably Vo/Li antigens. CA with anti-Pr and anti-Sa specificities recognize 0-glycans with immunodominant sialyl groups on glycophorins. Several Pr subspecificities can be identified by chemically modified sialyl groups on glycophorins. Because CA in chronic lymphoproliferation are monoclonal antibodies, structure-specificity-interrelations of the antibodies could be identified by primary structure analyses of the N-terminal variable regions of H and L chains and by studies on CA idiotypes. Interrelations between distinct CA specificities and particular infectious agents could explain cold agglutination as a response to receptors for the agents or to the binding sites of antibodies against the agents. Interrelations also existing between certain CA isotypes (Ig classes and L chain types) and CA specificities could be a basis for the elucidation of the enigmatic etiology of chronic (malignant) monoclonal cold agglutination.Transfusion Medicine Reviews 05/1989; 3(2):140-66. DOI:10.1016/S0887-7963(89)70075-4 · 4.54 Impact Factor