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Objective: To determine the prevalence of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in patients with systemic lupus erythematosus (SLE), and to assess their association with and predictive value for the clinical classification criteria of the antiphospholipid antibody syndrome (APS)., Methods: One hundred thirty-three consecutive patients with SLE were recruited from 2 lupus clinics in the University of Toronto. Serum and plasma samples were tested for IgG anticardiolipin antibodies (aCL), prolonged partial thromboplastin time (PTT), a panel of lupus anticoagulant (LAC) assays, and anti-beta2-GPI (IgG, IgM, IgA). Normal ranges for the assays were established using 129 healthy controls. A literature review from 1992 to 2000 was performed using beta2-GPI, SLE, APS, thrombosis, and recurrent pregnancy loss as key search words., Results: The distribution of anti-beta2-GPI antibodies (of any isotype) in each group were as follows: all patients with SLE, 36.8%; SLE with clinical features of APS, 40.4%; SLE without clinical features of APS, 34.9%; and healthy controls, 3%. The positive predictive values of prolonged PTT, IgG aCL, and anti-beta2-GPI for at least one clinical feature of APS in SLE were 59.3, 50.0, and 38.8%, respectively. There were 27 patients with SLE who had antibodies to beta2-GPI but a normal PTT and negative aCL and LAC. Six (20.7%) of these had a history of thrombosis and/or recurrent pregnancy loss. Twelve studies (including ours) were identified in which patient groups were similar and the same antibody isotype was measured. No agreement was apparent after reviewing the literature regarding an association of anti-beta2-GPI IgG and clinical features of APS in patients with SLE., Conclusion: Antibodies to beta2-GPI were frequently seen (35%) in our SLE population. The prevalence of anti-beta2-GPI was similar in those with (19/47) and without (39/86) APS. Anti-beta2-GPI did, however, identify 6 patients with clinical features of APS who were negative for aCL and prolonged PTT. Our results indicate that anti-beta2-GPI may provide additional information for the diagnosis of APS in SLE, but do not supercede other established assays. However, when we attempted to place our results in the context of other reports, the literature review revealed that secondary diagnoses of patient groups and assay techniques are too variable among different investigators to allow useful comparison. Thus, no conclusions could be drawn regarding anti-beta3-GPI and clinical features of secondary APS in SLE.

Background: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss., Methods: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy., Results: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02)., Conclusions: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Two different effects of maternal autoantibodies presented in a third-trimester pregnancy. The first was complete fetal heart block, demonstrated ultrasonographically, which correlated with the presence of anti-Ro and anti-La antibodies in the maternal serum. The second effect was decidual vasculopathy and thrombosis, a morphologic finding in the placenta that caused massive placental infarction and intrauterine death. The placental pathology correlated with the presence of anticardiolipin antibodies in the maternal serum at the time of stillbirth.

Purpose: To test the hypothesis that since only a proportion of heavy drinkers develop significant alcoholic liver disease (ALD), an autoimmune pathogenesis is likely., Patients and Methods: Autoimmune markers were measured in 47 patients with biopsy-proven ALD and compared to measurements in 20 alcoholics without clinical and hematologic evidence of ALD and 28 patients with autoimmune chronic active hepatitis (CAH)., Results: Twenty-two percent of patients with ALD were antinuclear antibody-positive, compared to 71% of patients with CAH. Approximately 60% of patients with ALD had either anti-single-stranded or anti-double-stranded DNA antibodies, slightly more than the patients with CAH. Another marker of autoimmunity, as in systemic lupus erythematosus, is the presence of IgM antibodies to autologous and heterologous lymphocytes, which are cytotoxic at 4 degrees C. Seventy-two percent of patients with CAH had positive antilymphocyte antibodies, compared to 59.6% of patients with ALD. Furthermore, more than 90% of the sera from ALD and CAH patients displayed lymphocytotoxicity. Thirty-two percent and 25.5% of CAH and ALD patients, respectively, had all three autoantibodies present., Conclusion: These results suggest that autoimmune mechanisms may indeed play a role in the pathogenesis of ALD in at least some patients.

Based on recent structural analyses of monoclonal autoantibodies, it appears that a number of these antibodies express germ-line immunoglobulin variable region (V) genes with little or no somatic mutation. In addition, our group and others have noted the identity or near identity of some autoantibody-associated V genes to V genes apparently expressed preferentially in the fetal pre-B cell repertoire. To extend these data, we now report that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny. Sequence comparisons indicate the likely use of fetal-restricted V genes by this autoantibody. Taken together with other data on autoantibody V gene usage, these findings provide further evidence for overlap between the autoantibody-associated and early ontogeny expressed V gene repertoires and suggest that natural autoreactivity may be instrumental in the development and maintenance of the normal immune repertoire.

Sera from patients in the acute and recovery stages of parvovirus B19 infection, and from individuals with no detectable antiparvovirus antibody were examined for the presence of anti-DNA and antilymphocyte antibodies. Sixty-eight percent of individuals recently recovered from parvovirus infection had elevated levels of antidouble stranded (ds) and antisingle stranded (ss) DNA antibodies. In addition, a cytotoxic IgM antilymphocyte antibody was detected in more than 88% of these same sera. Serial specimens from volunteers experimentally infected with parvovirus B19 were also tested for these autoantibodies and it was determined that the presence of antilymphocyte IgM was dependent on the stage of infection. The antilymphocyte IgM was occasionally detectable in sera containing rubella specific IgM (11%) or varicella zoster specific IgM (25%). However, in contrast to B19 infection, these antibodies were not cytotoxic. From the results of our study, we propose that parvovirus infection of hematologically normal individuals may be accompanied by a transient, subclinical autoimmune state.

Murine lupus is characterized by the production of numerous autoantibodies and immune complex glomerulonephritis. Anti-DNA antibodies are the hallmark of this disorder and may be associated pathogenetically with the glomerulonephritis. The cellular mechanisms underlying the regulation of the production of anti-DNA antibodies may prove to be the fundamental abnormalities responsible for the lupus syndrome seen in these mice. By using a system of spontaneous anti-DNA antibody production in vitro, we have determined that such production is characteristic of autoimmune NZB and MRL-lpr/lpr mice but not of the nonautoimmune control strains. Additional examination of the cellular mechanisms involved in the regulation of this response in NZB mice revealed: 1) this response is markedly T cell dependent, 2) NZB T cells are essential for maximal production of this autoantibody, and 3) NZB T cells actively interfere with normal immune regulatory mechanisms that lead to the production of anti-DNA antibodies spontaneously in vitro by nonautoimmune syngeneic B lymphocytes. Although these studies of anti-DNA antibody production in vitro disagree with previous work by others they successfully reproduce the results obtained earlier in experiments performed in vivo.