Antiphospholipid antibodies and fetal loss.
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Biomedical subjects
Publications and source records attributed to S Pierangeli.
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A soluble tumour-associated antigen was prepared by homogenizing AKR lymphoma cells (L15) followed by treatment with acetone and glycine-HCl buffer pH 3. It was analyzed by immunoelectrophoresis, rocket electrophoresis in the presence of Concanavalin A and SDS-PAGE. It showed rapid electrophoretic mobility, and the major component had an estimated molecular weight of 70,000 daltons. The molecular composition of the antigen included a glycoprotein. Specific antibodies against this antigen were demonstrated in BALB/c mice in which the AKR lymphoma was conditioned to grow by introducing the L15 cells into a subcutaneously implanted glass cylinder. In this model antibodies were found in both tumour-bearing (progressor) and tumour-rejecting (regressor) animals. In vivo experiments showed that pretreatment of BALB/c mice with L15 acellular extracts, 10 days before tumour challenge, led to a significant increase in allogeneic tumour growth. A rabbit anti-tumour extract serum was prepared and was rendered tumour -specific by exhaustive absorption with normal AKR serum and tissues. It shared the same epitopic specificity with tumour progressor or regressor mouse sera since indirect immunofluorescence using L15 cells could be reciprocally inhibited.
An experimental model was used in which AKR lymphoma cells (L15) were conditioned to grow in BALB/c mice leading to tumour-bearing (progressor) and tumour-rejecting (regressor) animals. The behaviour of antibodies present in the sera of these animals was studied using as antigen L15 cells or a soluble tumour-associated antigen TEs. Both sera showed similar IIF and haemagglutinating activity. However differences were observed for the complement cytotoxicity assay. Regressor serum as well as a rabbit anti-tumour-associated antigen serum were strongly cytotoxic for the AKR lymphoma cells while progressor serum showed markedly lower activity. Specific antibodies against the tumour-associated antigen were purified. In both sera they were located mainly in IgG1 but also in IgG2. The purified antibodies agglutinated specifically sensitized sheep erythrocytes and reacted by indirect immunofluorescence with L15 cells but not with AKR thymocytes. It is suggested that two qualitatively different humoral immune responses are involved in the mechanisms leading to tumour enhancement or rejection.
Antiphospholipid antibody, measured by enzyme-linked immunosorbent assay (ELISA) or by radioimmunoassay, and the lupus anticoagulant represent similar but different tests. The ELISA is now well standardized. It is at least partly, and possibly primarily, dependent on the presence of a cofactor, beta 2-glycoprotein I. Tests for both antiphospholipid antibody by ELISA and lupus anticoagulant should be performed in patients suspected of having this syndrome.
OBJECTIVE: Reports have shown that anticardiolipin (aCL) antibodies present in patients with autoimmune diseases are dependent on the cofactor,beta2 glycoprotein I (beta2 GPI), as opposed to aCL antibodies seen in infectious diseases such as syphilis, HIV hepatitis C, etc. The assay for anti-beta2GPI antibodies has been reported to be more specific for antiphospholipid syndrome (APS). However, the prevalence of these antibodies in diseases such as leishmaniasis and leptospirosis remains unknown. The aim of the present study was determine the prevalence of antibodies to cardiolipin and to beta2GPI in patients with different infectious diseases, including leptospirosis, syphilis and leishmaniasis. METHODS: Samples from patients with Kala-azar (visceral leishmaniasis), syphilis or leptospirosis were tested for IgG and IgM anticardiolipin and IgG anti-beta2GPI antibodies by ELISA. RESULTS: In patients with Kala-azar the prevalence of IgG aCL, IgM aCL and anti-beta2GPI was 6% (2/30), 3% (1/30) and 53% (16/30), respectively. In syphilis the prevalence was 18% (14/74), 13% (10/74) and 10% (8/70), respectively. In leptospirosis the frequency of these antibodies was 23% (9/39), 10% (4/39) and 17% (6/34), respectively. There was no statistical correlation between aCL and anti-beta2GPI antibodies in these diseases. DISCUSSION: This study clearly shows a significant prevalence of anti-beta2GPI antibodies in leptospirosis and leishmaniasis and syphilis. This indicates that the assay for antibeta2GPI antibodies should be thoroughly validated before it is introduced as a definitive tool for the diagnosis of APS, testing a larger number of sera from patients with a wider range of clinical conditions.
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