[Autoimmune diseases in pregnancy].
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Biomedical subjects
Publications and source records attributed to Y Shoenfeld.
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Strenuous work or sports activities in a hot environment can cause significant fluid and salt losses due to excessive sweating. Fluid replacement is commonly accepted to be beneficial, but controversy surrounds the necessity of adding salt to the dietary intake in hot climates. Five healthy young men participated in a self-controlled experiment designed to investigate the effects of salt loading on acclimatized people exercising under controlled laboratory conditions. The additional salt ingestion was found to cause an increase in body weight, rectal temperature, heart rate, urinary sodium and potassium concentrations and in the total amounts of sodium and chloride excreted in urine during the exercise. Furthermore, it decreased plasma aldosterone level and sweat chloride excretion, but did not affect fluid intake, urine output, sweat rate, skin temperature, excretion of sodium and potassium in sweat or urinary potassium content and chloride concentration. Neither did the additional salt intake affect plasma electrolyte levels, renin activity or acid base balance. It is concluded that acclimatized people living in a hot dry climate need no supplementary salt to their daily dietary intake while engaging in physical exercise or sports activities up to two hours a day. Salt loading has no beneficial effects in these conditions and may even be hazardous.
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Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.
Two out of 25 monoclonal anti-DNA autoantibodies that were produced by human-human hybridoma were found to have lymphocytotoxic activity. The antibodies reacted with normal B and T lymphocytes at cold (4 degrees C) as well as at warm (37 degrees C) temperatures. The lymphocytotoxic activity of the monoclonal anti-DNA antibodies could be inhibited by prior incubation of the antibodies with either polynucleotides, e.g. poly(I), poly(dT) or anti-idiotypic antibodies, that had been raised against a dominant anti-DNA antibody. The cross-reactivity between nuclear material and lymphocyte membrane raises the question whether these apparently diverse materials have a shared epitope. The cross-reactivity between anti-DNA antibodies and lymphocyte membrane may account in part for the lymphopenia observed in systemic lupus erythematosus patients.
Seven of 60 human monoclonal anti-DNA autoantibodies derived from 3 patients with SLE were shown to bind to Raji cells by radioimmunoassay. The binding of the lupus autoantibodies to the Raji cells in solution was not affected by prior incubation of the cells with DNase. Preincubation of the monoclonal autoantibodies with polynucleotides and cardiolipin, resulted in significant inhibition which correlated with the direct binding characteristics of these antibodies. Previous results with mouse IgG monoclonal anti-DNA antibodies supported by our results with human IgM anti-DNA autoantibodies suggest caution in interpreting analyses of immune complexes of sera containing anti-DNA antibodies entailing Raji cells.
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.
The general effect of pregnancy on autoimmunity remains controversial. In the majority of cases, pregnancy may have no effect on the disease, while on other occasions, pregnancy induces exacerbations that may be especially pronounced in the immediate post-partum period. The reasons for this preponderance are still unclear. Another important aspect of autoimmune diseases during pregnancy entails the passive transfer of the disease into the fetal compartment. It seems that until the pathogenesis and a better specific therapy for autoimmune diseases are clearly defined, careful clinical and immunologic observation of each mother-infant pair will be invaluable.
Benign familial leukopenia (BFL) is a hereditary phenomenon, encountered in several ethnic groups. Subjects bearing BFL are believed to be affected by bacterial infection in no greater incidence than normal subjects. In our study we investigated a group of subjects with BFL during an acute bacterial infection in comparison to subjects without BFL with the same infection. We found that the subjects with BFL had no absolute leukocytosis during the infection. Nevertheless, they reacted similarly to the other subjects in regard to their temperature and heart rate; however, they were hospitalized for fewer days than subjects without BFL. We conclude that BFL is a benign phenomenon, requiring neither specific treatment as such, nor more aggressive therapy during infection. The benign course of an acute bacterial infection in BFL indicates that perhaps the number of WBC's that are normally recruited during an infection in normal subjects highly exceeds that which is necessary.
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Monoclonal anti-DNA antibodies prepared by the hybridoma technique were used for an analysis of idiotypes of anti-DNA antibodies in systemic lupus erythematosus (SLE). Serum levels of one idiotypic marker, 16/6/R, were higher than normal in 40 of 74 patients (54%) with active SLE, compared with only 6 of 24 patients (25%) with inactive SLE, 9 of 38 patients (25%) with rheumatoid arthritis, and 4 of 96 normal subjects (4%). Levels of the 16/6/R idiotypic marker were determined in serially collected serum samples from 12 patients with SLE. Concordance was found between idiotype levels and clinical activity in 8 of the 12 patients. Levels of the 16/6/R idiotype tended to correlate with levels of antibodies to double-stranded DNA, but in some cases the clinical status was reflected better by the idiotype levels than by the levels of anti-double-stranded-DNA antibodies. Measurement of idiotypes of anti-DNA antibodies may provide information valuable in monitoring the clinical course of patients with SLE.