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Recent views on autoimmune diseases invoke generalized but specific perturbations in antibody repertoires, rather than the clonally restricted or non-specific polyclonal alterations proposed thus far. The present experiments analyse serum antibody reactivities in 24 systemic lupus erythematosus (SLE) patients and 17 healthy controls, using a method that quantitatively scores a large number of antibody reactivities and allows for multiparametric statistical analyses. The results show global but relatively specific perturbations in SLE antibody repertoires, and identify novel disease-associated reactivity patterns. Furthermore, a time series analysis of serum antibodies over 3 months demonstrates instability of natural antibody repertoires in individual SLE patients, contrasting with their remarkable conservation in healthy donors. Moreover, the method used clusters controls and patients independently, and might prove of diagnostic value, once large data bases are established.

Prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of pituitary prolactin secretion is complex and involves a negative feedback process in the hypothalamus, in which dopamine plays the principal role. However, the main source of serum prolactin in lupus patients is still not clearly established. Since homovanillic acid (HVA), the principal metabolite of dopamine (DA), is removed from the brain into the blood, it would indirectly reflect DA metabolism. It is assumed that the turnover of a neurotransmitter can be determined through an analysis of its metabolites. The objective of this study was to analyse plasma samples from SLE patients to see if there were any alterations in neurally functioning DA through its principal metabolite, HVA. We also measured the levels of PRL and compared HVA and PRL with the clinical activity of the disease. Twenty-four SLE patients and fifteen healthy controls were studied. The investigation was done over a period of 3 months. The results of this study show significantly low levels of HVA in lupus patients compared to controls (P < 0.0001). This corresponds to a decrease in dopamine turnover. Hyperprolactinemia was observed in nine patients, and the average level of prolactin in lupus patients was higher than in healthy controls (P < 0.001). For the duration of the study, a significant percentage of variation was observed in the levels of HVA in the clinically active patients (P < 0.05) compared to inactive patients. When PRL was compared in these groups, throughout the study, no significant percentage of variation was observed. The relationship between HVA and PRL in healthy controls was r = 0.47, P = 0.08, and in patients was r = 0.04, P = 0.84. It is suggested that there is a probable association between plasma levels of HVA and PRL in the healthy controls and not in the SLE patients.

1. A total of 450 hypertensive patients above the age of 60 years have entered the double-blind multicentre trial of the European Working Party on High blood pressure in Elderly (EWPHE). After stratification and randomization half were treated with one capsule daily containing 25 mg of hydrochlorothiazide and 50 mg of triamterene and half were given placebo. In those receiving active treatment, if blood pressure control was not adequate they were given a second capsule and if necessary up to 2 g of methyldopa/day. 2. No significant differences between the groups were present before randomization. A significant blood pressure difference of 25/10 mmHg was obtained between the groups and maintained during 4 years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. 3. During the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained during the later years. This increase in serum creatinine in the actively treated group was related (P = 0·003 and r = −0·247) to the decrease in sitting systolic blood pressure. Changes in serum uric acid were (r = 0·3 and P = 0·003) correlated with the changes in serum creatinine both in the placebo and in the actively treated group, but independent of the change in creatinine; the serum uric acid was on average 1 mg higher in the actively treated than in the placebo group. 4. Fasting blood glucose did not change significantly in the placebo-treated group but in the active treatment group the rise was statistically significant. 5. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. However, the balance between this decreased risk and the increased risk produced by the rise in blood glucose and the other treatment effects remains to be determined. Therefore the trial continues and more patients are being admitted.

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