Effect of interferon-gamma on B lymphocytes of patients with systemic lupus erythematosus

We studied the effect of interferon-gamma (IFN-gamma) on B cells in systemic lupus erythematosus (SLE). Low density B cells, which were fractionated on density gradients of Percoll, increased, and high density B cells decreased in number in SLE. Proliferative response of the high density B cells to interleukin 4 was reduced by IFN-gamma in normal controls, but not in SLE. IgG production of whole B cells induced by interleukin 2 or phytohemagglutinin induced T cell factors was enhanced by IFN-gamma in both normal controls and SLE in which activated B cells were thought to be increased in number. Therefore, IFN-gamma may be one of the factors which promote polyclonal B cell activation in SLE.     

The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia

We measured cerebrospinal fluid (CSF) levels of dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassay in seven patients with multi-infarct dementia (MID), fourteen age- and gender-matched non-demented patients with a history of cerebral infarction and fifteen age- and gender-matched patients without neurological disorders. The levels of DHEAS in CSF of patients with MID were significantly lower than those in non-demented patients with a history of cerebral infarction or those in patients without neurological disorders. Daily intravenous administration of 200 mg DHEAS for 4 weeks markedly increased serum and CSF levels of DHEAS in seven MID patients, improved decrease of daily activities and emotional disturbances in three patients and EEG abnormalities in two patients. The DHEAS therapy may provide a beneficial effect on MID patients.     

Defects in antigen-driven lymphocyte responses in common variable immunodeficiency (CVID) are due to a reduction in the number of antigen-specific CD4+ T cells.

T cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette-Guérin (BCG) was reduced to 1 in 109,000 T cells compared with 1 in 18,600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells.     

The role of circulating immune complexes in the pathogenesis of Graves' disease

It has recently been reported that many immunological abnormalities including the presence of TSH-receptor antibody (TRAb) were found in Graves' disease (GD). Circulating immune complexes (CIC) have also been detected in the serum of patients with GD as observed in systemic lupus erythematosus, which is thought to be a typical model of immune complex disease. The role of CIC in pathogenesis of hyperthyroidism, however, remains to be elucidated. Therefore, to clarify pathophysiological functions of CIC in GD, the levels of it in those patients were compared with their symptoms, those of TRAb, and lymphoblastogenesis (LBG) induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The subjects were forty patients with GD without any medication, one hundred and nine patients with GD on medication with methimazole (MMI), and fifteen healthy volunteers. CIC was measured by three different methods; polyethyleneglycol precipitation method (PEG), Clq binding assay (Clq), and Protein A binding assay (PA). The normal range was estimated with the mean plus or minus two times the standard deviation of normal controls. In untreated GD, CIC determined by PEG, Clq and PA widely distributed from normal range to high levels. The positive rates of CIC determined by PEG, Clq, PA, and any one method of these three were 17.5%, 22.5%, 30.0% and 52.5%, respectively. LBG using incorporation of tritiated thymidine showed the decreases in PHA and Con A, and the increases in PWM in patients with GD. The positive rates of CIC determined by PEG and PA were significantly higher in patients without goiter or with small one than those with large one (p less than 0.05). CIC measured by all three of PEG, Clq and PA showed negative correlation with TRAb significantly (p less than 0.05, p less than 0.01, p less than 0.01, respectively). On the other hand, CIC measured by Clq showed significant negative correlation with serum thyroxine concentration (p less than 0.01). The levels of CIC, TRAb and PWM-induced LBG decreased following the tapering dose of MMI sufficient to keep patients in euthyroid state. In consequence, there were no longer any correlations between CIC and TRAb after thyroid function was normalized. These observations suggest that CIC's which have huge molecular weight or have ability to bind Fc receptor on K cell, macrophage, neutrophil, and other immune cells may be one of the factors to inhibit the goitrogenic action of TRAb, and that CIC's which have ability to activate the complement system may be one of the factors to inhibit the stimulation of secretion of thyroid hormone by TRAb.(ABSTRACT TRUNCATED AT 400 WORDS)