Complement activation in Ghanaian children with severe Plasmodium falciparum malaria.
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BACKGROUND: Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001). CONCLUSION: These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding. (+info)
Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice.
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When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results. (+info)
Detection of Rh antibodies using two low ionic diluents: extension of the incubation time and the number of Rh antibodies detected.
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BACKGROUND: Low ionic strength solution (LISS) is used to increase the rate of association of antibody to the corresponding antigen during antibody detection tests. A number of LISSs are available on the market. AIMS: The efficiency of two commercial low ionic diluents, DiaMed ID-CellStab and Inverclyde LISS were assessed using the DiaMed-ID LISS Coombs microtube column system and an incubation time varying from 15 to 35 min. MATERIALS AND METHODS: One-hundred samples containing five Rh antibodies (anti-D, anti-C, anti-E, anti-c and anti-e) were tested against commercial red cells using the two low ionic diluents after 15, 25 and 35 min. RESULTS: The Inverclyde LISS detected 91, 95 and 96% of the Rh antibodies compared to 78, 79 and 83% for ID-CellStab after 15, 25 and 35 min incubation time, respectively, for both methods. CONCLUSIONS: The Inverclyde LISS is a more suitable and efficient diluent than ID-CellStab for the detection of Rh antibodies. The sensitivity of Rh antibody detection increased for the both methods as the incubation time increased. (+info)
Evaluation of seven tests for diagnosis of human brucellosis in an area where the disease is endemic.
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An unusual case of acute brucellosis presenting with Coombs-positive autoimmune hemolytic anemia.
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Brucellosis can mimic several primary hematological diseases. Mild anemia and leukopenia have been frequently associated with acute brucellosis, but pancytopenia, thrombocytopenia, and hemolysis are less frequently seen. To our knowledge, brucellosis has not previously been described in association with Coombs-positive autoimmune hemolytic anemia. Here, we report a case of acute brucellosis presenting with coombs-positive autoimmune hemolytic anemia. The patient responded well to short-term pulse corticosteroid therapy followed by antibrucellosis treatment. We suggest that Brucella infection may be the probable cause of the immune hemolytic anemia in this patient. Therefore, the differential diagnosis of Coombs-positive autoimmune hemolytic anemia should include brucellosis, especially in areas where the disease is endemic. (+info)
The role of the direct antiglobulin test in pre-transfusion investigations and the approach to selecting blood for transfusion in autoimmune haemolytic anaemia: results of a regional survey.
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INTRODUCTION: The aim of this study was to conduct a Regional survey to determine the policies and ways of performing the direct antiglobulin test in pre-transfusion screening, the approach used in cases giving positive results with this test and the technical and operative modalities for choosing blood for transfusion in cases of autoimmune haemolytic anaemia. MATERIALS AND METHODS: A questionnaire, containing ten multiple-choice questions, was sent to all the transfusion centres in the Region of Tuscany. RESULTS: The data from all 40 regional centres were analysed. Direct antiglobulin tests and autocontrols were not regularly used in pre-transfusion screening. The direct antiglobulin test was predominantly reserved for suspected cases of autoimmune haemolytic anaemia. Sixty percent of the laboratories characterised the specificity of samples that were positive for IgG and complement by the direct antiglobulin test, 45% that were positive for IgM, 35% also for IgA, and 13% also for subclasses of IgG. Elution studies were reserved (in 18% of laboratories) for those cases in which it was expected that transfusion therapy would be used. In cases of autoimmune haemolytic anaemia, autologous/allogeneic adsorption was carried out in 27% of the structures (the use of proteolytic enzymes is predominant, followed by the "ZZAP" reagent--a mixture of dithiothreitol and an enzyme) and the dilution method in 20%; transfusion of red blood cells with a phenotype extensively compatible (c, C, D, E, e, K, Jka, Jkb, Fya, Fyb, S, s) with that of the recipient is practised in 17% of the centres, while transfusion of units of "least incompatible" red blood cells was reported by 95% of the centres, but in 88% this is preceded by at least one of the above mentioned immunohaematological investigations. CONCLUSIONS: The organisation of a network of Services of Immunohaematology and Transfusion Medicine can be exploited to overcome some technical and operative limitations of peripheral, dependent Transfusion Sections. The results of this study reveal which immunohaematology laboratory is endowed with the greatest potential and which could, therefore, become the regional reference centre. This investigation could lay the basis for defining behavioural algorithms and recommendations on the issues considered. (+info)
Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in F1 (BALB/c X NZB) hybrid mice derived by ovum transplantation.
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F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information. (+info)
Interference by heterophilic antibodies in immunoassays: wrong increase of myoglobin values.
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Aim of this work is to illustrate how analytical interference in immunoassay may produce serious errors in clinical laboratory results. The sophisticated quality assurance schemes used in many laboratories do not identify erroneous results arising from aberrant samples. Recently attention has been focused on the incidence and implication of false-positive results arising from the presence of certain substances in a patient's serum that interfere with one or more steps in immunoassays. In this paper, we present the case of a 92 year-old woman whose plasma myoglobin concentrations falsely increased when measured using the Beckman Access assay. We demonstrated that heterophilic antibodies accounted for the falsely increased myoglobin values, and we suggest how to resolve such situations. (+info)