HLA-DR in chronic idiopathic thrombocytopenic purpura (ITP).
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Biomedical subjects
Publications and source records attributed to C Mueller-Eckhardt.
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To evaluate the applicability of a radioactive 125I-anti-IgG test (RIAT) for the detection of small amounts of IgG antibodies on red blood cells (RBC) of patients with autoimmune hemolytic anemia of warm type (AIHA), RBC of 125 patients were studied (AIHA, n = 53; Coombs'-negative AIHA, n = 6; chronic cold agglutinin disease, n = 7; non-immune anemias, n = 59). It was found that the RBC of all cases (33/33) with a positive direct IgG antiglobulin test (DAT-IgG), but also 13 out of 20 patients with a negative DAT-IgG, but detectable complement (C3/C4), and 4 out of 6 cases with Coombs'-negative AIHA gave positive results in the direct RIAT. RBC-associated IgG was higher in the DAT-IgG positive group (n = 33; -x = 8.1%) than in the DAT-IgG negative group (n = 26; -x3.4%). There was no correlation between hypergammaglobulinemia and RBC-associated IgG. The sensitivity of the indirect RIAT was not remarkable better as compared to the indirect antiglobulin test. The RIAT is valuable in the serology of borderline cases of AIHA.
Blood cell separators have been successfully used in the treatment of chronic leukaemias. With the intermittent flow system Haemonetics model 30, we found it important to collect 150-300 ml buffy coat/cycle in order to obtain a substantial depletory effect. In 2 patients with chronic myeloid leukaemia on short-term leukapheresis and in 1 patient with prolymphocytic leukaemia on long-term leukapheresis we found a definite decrease in the WBC count. 2 of them experienced a transitory improvement of their disease. Only minor side-effects occurred. However, the loss of erythrocytes and plasma albumin necessitated replacement therapy. From our experience the intermittent flow blood cell separator can be successfully used in the treatment of well-defined forms of chronic leukaemia.
The role of platelet alloimmunization in the survival of 51Cr-labeled allogeneic platelets was investigated in 89 patients with severe thrombocytopenias. The serological analysis included HLA typing of patients, screening of their sera in the lymphocytotoxicity test (LCTT), the platelet complement fixation test (PCFT), and the platelet radioactive anti-IgG test (PRAT; N = 38). Platelet donors were selected according to the best available HLA match and crossmatch in LCTT. Alloantibodies against HLA antigens were found in the sera of 17 patients (19.1%). No platelet-specific alloantibodies were detected. The use of compatible, allogeneic platelets permitted the discrimination of diminished platelet production from increased platelet turnover in thrombocytopenic patients with proven alloimmunization. Our results stress the necessity of a serological workup prior to platelet survival studies.
Two patients with post-transfusion thrombocytopenic purpura are described, the first cases recognized in Austria and Germany. Both patients were female, 51 and 60 years of age. The purpura was evoked by blood transfusions with a latent period of 2 and 7 days. The thrombocytopenic episode lasted for 22 and 60 days. In one case, thrombocytopenia was associated with agranulocytosis due to transient bone marrow failure. Both patients were negative for the platelet-specific antigen PlA1 (= ZWa). Their sera contained PlA1 as well as potent HLA antibodies. Detailed clinical and serological data are presented. The literature with a total of 25 cases so far reported is surveyed.
Platelet-associated IgG (PAIgG) was studied by a quantitative platelet radioactive anti-IgG test (PRAT) in 298 patients. At the time of investigation, 171 patients were thrombocytopenic (platelet count < 100 X 10(9)/l), 127 had normal platelet counts. Patients fell into the following disease categories: Idiopathic thrombocytopenic purpura (ITP) (N = 81), possible ITP (19), acute ITP (9), systemic lupus erythematosus (22), autoimmune haemolytic anaemia of warm-type (18), systemic blood disease (65), liver diseases (35), other (49). A significant elevation of PAIgG was found in all disease categories. There was a significant correlation between PAIgG and the reciprocal values of platelet counts for most disease groups. No relationship was discernible between PAIgG and hypergammaglobulinaemic states (serum IgG > 1.8 g/l). Platelet survival studies (N = 30) revealed that normal and increased values of PAIgG were associated with normal or shortened platelet mean life span. It is concluded that an elevated PAIgG is only one of several factors involved in the development of immunologically medicated thrombocytopenia.
The direct demonstration of HLA-C antigens Cw2, Cw-3, and Cw4 on human platelets is described. The antigens were detected by means of a platelet radioimmune anti-IgG test using acid eluates from platelets and lymphocytotoxic antisera. It is concluded that HLA-C determinants are only weakly expressed on platelets. Individual differences observed reflect antigenic variations.
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This article reviews in detail our present knowledge concerning the pathogenesis, clinical picture and therapy of the most serious complications of blood transfusion (the hemolytic transfusion reaction, the febrile transfusion reaction, the acute posttransfusion pulmonary syndrome, the posttransfusion purpura, the anaphylactic transfusion reaction and the "posttransfusion" hepatitis). Recent literature is quoted.
The diagnosis of immunologically caused platelet deficiencies in newborn infants requires use of methods permitting demonstration of platelet auto- and allo-zntibodies, complete and incomplete antibodies. Taking the well known differentiation of neonatal immunothrombocytopenias into auto- and allo-immune diseases as a basis, the immune-haematological findings in eight cases are reported. For the first time two cases are reported in which both idiopathic thrombocytopenic purpura of the mother was known and allo-immunisation against paternal HLA antigens of the child could be demonstrated.
The effect of washed human platelets, platelet lysates, and platelet antibody complexes on 14C-thymidine incorporation by human lymphocytes was studied. For sensitization of platelets, HLA-specific alloantibodies as well as platelet autoantibodies were used. Lymphocytes for in vitro cultures were collected from unsensitized individuals, healthy women with proven fetomaternal immunization against HLA antigens and patients with idiopathic thrombocytopenic purpura (ITP). Unsensitized platelets have a dose-dependent inhibitory effect on the in vitro proliferation of normal lymphocytes induced by mitogens (PHA, ConA, PWM). Platelet antibody complexes (allo- and autoantibodies; allogenic and autologous lymphocyte-platelet combinations) did not stimulate 14C-thymidine incorporation. Lymphocytes from ITP patients showed a significantly reduced stimulatory response toward PHA compared to normal persons. These findings are discussed in the light of our present knowledge regarding the role of cellular immune reactions in the pathogenesis of ITP.
The case of an 18-year-old male patient with aplastic anemia is reported who was successfully treated by platelets from his father, mother and uncle over a period 8 months because of the very rare constellation of HLA-A,B identity in the family. The patient deceased from uncontrollable septicemia.
79 patients with definite ITP were investigated for HLA-A, -B, -C antigens. There was an increased frequencey of HLA-B5 in the entire groups (27.8% vs. 16.5% in controls and for HLA-B12 in male patients. However, after correction for the number of antigens tested, the difference of antigen frequencies became insignificant.
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Eight female patients with drug-induced agranulocytosis (five patients with definite seropositive rheumatoid arthritis (RA), three patients with upper respiratory infections) were studied for the presence of HLA-B27 and antinuclear antibodies (ANA). Five of eight patients were found to be HLA-B27 positive and all RA patients had ANA in their serum. The frequency of HLA-B27 and ANA was found to be significantly different from control groups. It is concluded that the occurrence of HLA-B27 and ANA was found to be significantly different from control groups. It is concluded that the occurrence of HLA-B27 in female patients with seropositive RA (especially in those with ANA) and of HLA-B27 alone in other individuals could reflect an increased risk for drug-induced agranulocytosis.
A platelet radioactive antiimmunoglobulin test (PRAT) has recently been introduced. In the present report, a detailed analysis the influence of varying test conditions (i.e. efficiency of iodination of anti-IgG, cell number, degree of sensitization of platelets, times and temperatures of incubation, frequency of washings) on the results of this technique is presented. A standard procedure based on these findings is outlined. It is shown that the PRAT is two to four times more sensitive than platelet complement fixation for the detection of HLA antibodies.
It is shown that the 125I-anti-immunoglobulin test with platelets is as sensitive and reproducible for the detection of quinidine-associated antibodies as platelet complement fixation. Because of its independence from complement activation, this test might prove most valuable for the demonstration of non-complement-fixing, drug-associated antibodies.
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