Antinuclear antibodies in the serum of normal pregnant women: a prospective study.

A prospective study was performed to determine the incidence of antinuclear antibodies in 214 normal pregnant women and in 50 age-matched controls. Serum samples of 23 pregnant women (10.7%) yielded positive results (1 + or more at a dilution of 1:20) in contrast with only one sample (2%) in the control group (p less than 0.05). Of the pregnant women found to be positive, five (9.2%) were in the second trimester, and 18 (13.4%) were in the last trimester. Only two also had positive anti-DNA antibodies. A review of their hospital records disclosed no reason to suspect systemic lupus erythematosus or other rheumatologic diseases nor any significant increase in neonatal morbidity of their infants. We conclude that the incidence of antinuclear antibodies in pregnant women is significantly higher than in nonpregnant women and that the finding probably does not correlate with any adverse clinical effect.

Sjögren's syndrome presenting with hypereosinophilia, lymphopenia and circulating immune complexes.

Although mild peripheral eosinophilia is a common finding in Sjögren's syndrome (SS), severe eosinophilia with a clinical picture simulating hypereosinophilic syndrome is extremely rare. We report a 24 year old male with SS presenting with swelling of the parotid glands, redness and irritation of the eyes, polyarthralgias and polyarthritis, weight loss, exertional dyspnea, malaise, erythematous and urticarial skin lesions and enlarged lymph nodes. Laboratory tests showed hypereosinophilia (34%, total 3800/mm3), lymphopenia (2%, total 220/mm3), a positive RA factor (1:2560) and decreased C3 and C4. Biopsy of an enlarged submaxillary gland was consistent with SS. A Schirmer test showed decreased tear production. Salivary glands showed a marked decrease in uptake of radioactive (Tc99) dye. Circulating immune complexes (CIC) were markedly elevated by both C1q binding and Raji cell assays. T-cell subsets showed OKT3 = 63%, OKT4 = 32% and OKT8 = 16%. "Histamine trap" in vivo test for CIC revealed fluorescence in upper dermal blood vessels with IgM, C1q, C3 and fibrin. Biopsies of the liver, bone marrow and skin revealed eosinophilic infiltration. A notable response to therapy with high doses of corticosteroids was seen with recurrence of symptoms and laboratory abnormalities after the therapy was stopped. In conclusion, we present a case of SS which is remarkable for the age and sex of the patient, extreme hypereosinophilia, marked lymphopenia, and CIC.

Defective expression of OKT4 antigen on the cell surface of helper T lymphocytes in a patient with systemic lupus erythematosus.

OKT-monoclonal antibodies directed to total T-cells (OKT3), inducer/helper (OKT4) or suppressor/cytotoxic (OKT8) T-cells recognize developmental antigens on human T-cells. We report here an 18 year old male patient with systemic lupus erythematosus who had a prominent decrease in the proportion of OKT4-reactive T-cells in his peripheral blood, although the proportion of OKT3- and OKT8-reactive T-cells were essentially normal. His peripheral blood lymphocytes (PBL) responded well to stimulation by phytohemagglutinin-P (PHA) or concanavalin-A (Con A), which are stimulators for OKT4-reactive T-cells or for both subsets. Furthermore, helper T-cell function for B-cell proliferation was demonstrable in the patient's T-cells which lacked both OKT4 and OKT8 antigens. Trypsinization of PBL from healthy individuals abrogated detection of the OKT4 antigen, and a complete recovery of the antigen was observed after 6 days of culture of the treated PBL. The OKT4 antigen, however, could not be expressed on the patient's PBL after this treatment and incubation. In addition, the patient's serum could not block the recovery of OKT4 antigen on trypsinized T-cells from healthy individuals. The decrease in the percentage of OKT4-reactive T-cells was relatively stable in the patient, while his clinical disease activity and medications were variable. Taken together, these results suggest a defective expression of OKT4 antigen on the helper T-cell subset in this patient.

Further characterization of mitogen-induced autorosette-forming cells: correlation with T-cell subsets and with lymphocyte proliferative responses to mitogens.

Spontaneous autologous rosette-forming cells (ARFC), which form rosettes with autologous erythrocytes, have been of interest as a subset of thymus-derived lymphocytes (T cells). An association of these cells with concanavalin A (Con A)-induced ARFC has been suggested. Furthermore, the Con A-induced ARFC have been shown to be a suppressor T-cell subset in the Con A-generated suppressor system. We have previously reported the induction of ARFC from T cells by several T-cell mitogens such as phytohemagglutinin-P (PHA) and allogeneic non-T cells other than Con A. In the present report, we further characterized the mitogen-induced ARFC and have extended the study to patients with systemic lupus erythematosus (SLE). We have found that ARFC are also inducible from peripheral blood T cells by pokeweed mitogen (PWM). Studies of T-cell surface markers on the ARFC using OKT monoclonal antibodies confirmed the induction of ARFC from both OKT4- and OKT8-reactive T cells by either Con A, PHA, or PWM stimulation. However, OKT4-reactive T cells were the major cellular source of the ARFC induced by all of the mitogens. In studies of SLE patients, proportions of both Con A- and PWM-induced ARFC were found to be significantly low in PBL of SLE patients treated with moderate or large doses of prednisone, with or without concomitant immunosuppressants, but not in SLE patients without such treatment. Proportional analysis of the T cells and their subsets suggested association of these alterations in the mitogen-induced ARFC with the OKT4-reactive T cells, since a significant decrease in the OKT4-reactive T-cell subset was demonstrated in the PBL of these patients. Proportions of PHA-induced ARFC, however, were not significantly different between SLE patients and healthy adults. Moreover, positive correlations of the mitogen-induced ARFC with lymphocyte proliferative responses to each mitogen were established in both SLE patients and healthy adults. These results further support our previous observation that suggest the receptors for autologous erythrocytes are enhanced or reexpressed on those T cells which are highly activated by mitogens.

Thymosin administration in autoimmune disorders.

Five patients with autoimmune disorders were given thymosin, fraction 5, parenterally for periods ranging from 2 to 35 mth. Four patients had systemic lupus erythematosus and the 5th had rheumatoid arthritis and Sjögren's syndrome. Treatment with thymosin was based on the hypothesis of a T-suppressor defect in these autoimmune disorders. Circulating T lymphocytes increased and remained above pretreatment levels in all patients. Assays for cytotoxicity, using mouse thymocytes and patients' sera, were positive initially and declined during the course of the treatment. In all patients, serum cytotoxicity levels were reduced to zero. There has been clinical improvement in 3 patients, and in 1, the disease has become stable. The evaluation of the 5th patient has been inconclusive. No ill effects related to the administration of thymosin were observed.