A Combination of IgG and IgM Autoantibodies in Chronic Cold Agglutinin Disease: Immunologic Studies and Response to Splenectomy

Vox Sanguinis (Impact Factor: 2.8). 02/1985; 48(2):105-9. DOI: 10.1111/j.1423-0410.1985.tb00153.x
Source: PubMed


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.

6 Reads
  • [Show abstract] [Hide abstract]
    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 · 2.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The technique of human-human (H + H) hybridoma is employed to generate human monoclonal antibodies. However, in contrast to mouse hybridomas, the human counterpart is very difficult to establish. It is still unclear what the precise reasons are for the failure to establish the human-human hybridoma technique as a routine. Analyses of HLA antigens of seven lymphocyte donors and 22 human cell lines generated by the H + H hybridoma technique have demonstrated the importance of the compatibility between human lymphocytes and the lymphoblastoid cell lines. Furthermore, there is a preferential expression of several HLA on human hybridomas (e.g. B51; B15; B18; B35). Screening several unrelated human lymphoblastoid cell lines available demonstrated preferred HLA antigens (A2, A3; A30/31; B5; B18; B15; B35), despite the fact that these lines were derived from subjects of different ethnic origins. It seems that HLA typing of donor lymphocytes and lymphoblastoid cell lines may help to increase the yield of H + H hybridomas.
    Tissue Antigens 11/1988; 32(4):209-14. DOI:10.1111/j.1399-0039.1988.tb01657.x · 2.14 Impact Factor
  • [Show abstract] [Hide abstract]
    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 · 3.23 Impact Factor
Show more