IgM class autoantibodies in human cord serum.

It has previously been shown that human neonatal B lymphocytes in vitro can synthesize autoantibodies which typically are of IgM class, polyreactive and of low affinity and thought to represent natural autoantibodies. We screened 1034 cord serum specimens to find sera with elevated IgM levels; 98 such sera were further examined by an enzyme-linked immunosorbent assay (ELISA) to determine whether antibodies against a panel of autoantigens could be found. We detected low levels of IgM class antibodies against cardiolipin, pyruvate dehydrogenase, single-stranded DNA, thyroglobulin and Fc fragments of IgG as rheumatoid factors. The IgM concentration correlated with autoantibody levels. The specificity of the autoantibody assays was confirmed by inhibition tests. We conclude that several types of autoantibodies can be found in some sera of newborns and that increased IgM concentration of some neonates may reflect a polyclonal antibody response.

Antibodies to oxidized low-density lipoprotein and to cardiolipin in nonpregnant and pregnant women with habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to oxidized low-density lipoprotein (LDL) in women with a history of habitual abortion before and during pregnancy. DESIGN: Immunoglobulin G class antibodies to malondialdehyde modified LDL were determined by a solid-phase ELISA in 42 habitual aborters before pregnancy, in 39 patients during pregnancy, and in 23 comparable nonpregnant and 22 pregnant control women without a history of abortion. In addition, we assessed the presence of anticardiolipin antibodies by ELISA in the same sera. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Early pregnancy was accompanied by a decrease in the median levels of antibodies to oxidized LDL both in habitual aborters and in the control series. Only one patient exhibited a raised level of antibodies to oxidized LDL before pregnancy but, during pregnancy, nine patients (23%) had elevated levels of antibodies to oxidized LDL, similar to women with a favorable outcome of pregnancy (6/27, 22%) and in women whose current pregnancy also ended in abortion (3/12, 25%). Cardiolipin binding antibodies were detected in three habitual aborters before pregnancy (7%) and in nine women during pregnancy (23%), with a tendency to be more frequent in patients with miscarrying pregnancies than in those with continuing pregnancies (4/12, 33% and 5/27, 19%). Antibodies to oxidized LDL and cardiolipin were simultaneously present in three habitual aborters with continuing pregnancies. CONCLUSIONS: Increased levels of antibodies to oxidized LDL and cardiolipin may be associated with habitual abortion.

Antibodies to beta 2-glycoprotein I and prothrombin in habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to beta 2-glycoprotein I (beta 2-GP-I) and prothrombin in women with histories of habitual abortions when pregnant and nonpregnant. DESIGN: Antibodies to beta 2-GP-I and prothrombin were measured by ELISA using irradiated polystyrene plates in 43 women with habitual abortions and 22 healthy controls. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki. PATIENT(S): Twenty-two women of the habitual abortion patients had never delivered (primary aborters) and 21 had delivered at least one living child before miscarriage (secondary aborters). INTERVENTION(S): Venous blood samples were collected before and during pregnancy. MAIN OUTCOME MEASURE(S): Immunoglobulin G class antibodies to beta 2-GP-I and prothrombin. RESULT(S): The secondary aborters showed higher levels of antibodies to prothrombin than the primary aborters when both pregnant and nonpregnant and also showed higher levels of antiprothrombin antibodies than the controls when pregnant. No such differences were found in levels of antibodies to beta 2-GP-I. The habitual abortion patients showed a tendency toward higher levels of these autoantibodies when pregnant than when nonpregnant. Gestational diabetes was more common among the antibody-positive habitual abortion patients than among the antibody-negative patients. CONCLUSION(S): Increased levels of antiprothrombin antibodies were associated with secondary abortions. Elevated levels of antibodies to beta 2-GP-I and prothrombin often were found in habitual abortion patients with gestational diabetes.

A follow-up study of immunoglobulin levels and autoantibodies in an unselected pregnant population.

PROBLEM: To obtain a systematic view of changes in the levels of immunoglobulins (Igs), other serum proteins, and autoantibodies during pregnancy and postpartum. METHOD: A series of 220 women were followed throughout pregnancy and four to six months postpartum. RESULTS: Immunoglobulin G (IgG) concentration clearly decreased toward term. The concentrations of IgM and IgA decreased only slightly. In most instances autoantibody levels paralleled changes in the corresponding immunoglobulin class levels. In few cases, however, there were clear deviations from this. With respect to IgG class autoantibodies, the highest autoantibody levels were found in the postpartum specimen. IgM class autoantibody levels remained almost constant throughout the follow-up period. CONCLUSIONS: The intrapregnancy decrease of IgG is mainly due to hemodilution, but when the effect of hemodilution is taken into account, total amounts of IgM and IgA are increased. The results suggests that compared to IgG the regulatory mechanisms of IgM and IgA are altered during pregnancy.

Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared.

Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters.

Demonstration of antibodies to mosquito antigens in man by immunodiffusion and ELISA.

Cutaneous reactions to mosquito bites are believed to be immunologically mediated, but knowledge of the underlying mechanisms is very limited. In the present work, comprising 598 subjects, we show that precipitating and ELISA-reactive IgG-class antibodies occur frequently in the adult population. The operating antigen(s) were found in whole-body extracts of Aedes mosquitoes and also in a continuous mosquito cell line culture. The appearance of antimosquito antibodies seems to be correlated with the exposure to mosquito bites; however, massive exposure at an early age may result in a suppressed response.

Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.

Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.