Objective Amerindian-Europeans, Asians and African-Americans have an excess morbidity from SLE and higher prevalence of lupus nephritis than Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and socio-demographic characteristics and clinical features in a large cohort of Amerindian-European SLE patients. Methods A total of 2116 SLE patients of Amerindian-European origin and 4001 SLE patients of European descent with clinical data were used in the study. Genotyping of 253 continental ancestry informative markers was performed on the Illumina platform. The STRUCTURE and ADMIXTURE software were used to determine genetic ancestry of each individual. Correlation between ancestry and socio-demographic and clinical data were analyzed using logistic regression. Results The average Amerindian genetic ancestry of 2116 SLE patients was 40.7%. There was an increased risk of having renal involvement (P<0.0001, OR= 3.50 95%CI 2.63-4.63) and an early age of onset with the presence of Amerindian genetic ancestry (P<0.0001). Amerindian ancestry protected against photosensitivity (P<0.0001, OR= 0.58 95%CI 0.44-0.76), oral ulcers (P<0.0001, OR= 0.55 95%CI 0.42-0.72), and serositis (P<0.0001, OR= 0.56 95%CI 0.41-0.75) after adjustment by age, gender and age of onset. However, gender and age of onset had stronger effects on malar rash, discoid rash, arthritis and neurological involvement than genetic ancestry. Conclusion In general, genetic Amerindian ancestry correlates with lower socio-demographic status and increases the risk for developing renal involvement and SLE at an earlier age of onset.

BackgroundA protective role for glucocorticoid therapy in animal models of sepsis was shown many decades ago. In human sepsis, there is new interest in glucocorticoid therapy at a physiological dose after reports of improved response to vasopressor drugs and decreased mortality in a selected group of patients. However, other reports have not confirmed these results. Cellular glucocorticoid resistance could explain a possible cause of that. To evaluate this hypothesis, we evaluated the expression of glucocorticoid receptor beta, the dominant negative isoform of glucocorticoid receptor, in peripheral mononuclear cells of septic patients and the effect of serum septic patients over glucocorticoid receptor expression and glucocorticoid sensitivity in immune cells culture.MethodsA prospective cohort study and an in vitro experimental study with matched controls were developed. Nine patients with septic shock and nine healthy controls were prospectively enrolled. Mononuclear cells and serum samples were obtained from the patients with sepsis on admission to the Intensive Care Unit and on the day of discharge from hospital, and from healthy volunteers matched by age and sex with the patients. Glucocorticoid receptor alpha and beta expression from patients and from immune cell lines cultured in the presence of serum from septic patients were studied by western blot. Glucocorticoid sensitivity was studied in control mononuclear cells cultured in the presence of serum from normal or septic patients. A statistical analysis was performed using a Mann-Whitney test for non-parametric data and analysis of variance for multiple comparison; P < 0.05 was considered significant.ResultsThe patients' glucocorticoid receptor beta expression was significantly higher on admission than on discharge, whereas the alpha receptor was not significantly different. In vitro, septic serum induced increased expression of both receptors in T and B cells in culture, with a greater effect on receptor beta than the control serum. Septic serum induced glucocorticoid resistance in control mononuclear cells.ConclusionThere is a transient increased expression of glucocorticoid receptor beta in mononuclear cells from septic patients. Serum from septic patients induces cell glucocorticoid resistance in vitro. Our findings support a possible cell glucocorticoid resistance in sepsis.

Although bovine and ovine descending colon absorbed solute and sodium at approximately the same rate in vitro, water absorption by bovine colon was faster (15.0 +/- 2.0 microliters.h-1.cm-2, n = 8) than by ovine colon (8.6 +/- 1.3 microliters.h-1.cm-2, n = 9; P less than 0.01). Consequently, the observed osmolality of cattle absorbate was lower (364 +/- 13 mosmol/kg, n = 8) than with sheep (807 +/- 135 mosmol/kg, n = 9; P less than 0.01). Paracellular permselectivity was examined to elucidate this difference; the permeability of bovine descending colon to [3H]polyethylene glycol 400 and 4000 was higher than in sheep (P less than 0.001). A paracellular solvent drag was observed in bovine but not in ovine colon, and the electrical resistance of bovine colon was lower (16.0 +/- 1.4 omega.cm2) than ovine colon (28.0 +/- 2.4 omega.cm2; P less than 0.001). Pore radii of 2.5 nm for ovine and 5 nm for bovine colonic paracellular route were estimated from these data. It is concluded that an increased hydraulic conductance of the "active" route for solute absorption combined with raised solute reflux via the wider paracellular pathway may account for the failure of cattle to form a hypertonic absorbate and, consequently, hard feces.

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Previous studies have suggested that an alteration in the expression of the NaK-ATPase of muscle may be an important determinant of enhanced insulin sensitivity in chronic renal failure. Therefore, in the present studies we have examined the effect of uremia on the NaK-ATPase a isoforms in skeletal muscle, at the level of mRNA expression and enzymatic activity. The activity of the sodium pump, as measured ouabain-sensitive 'Rb/K uptake in soleus muscle, revealed a reduction in the activity in uremia, related to the increment in plasma creatinine values. The decrement in 86Rb uptake by the rat soleus muscle of experimental animals was associated with changes on NaK-ATPase gene product. Northern analysis of mRNA revealed isoform-specific regulation of Na,K-ATPase by uremia in skeletal muscle: a decrease of -50% in al subunit Na,K-ATPase mRNA, as compared to controls. The decrement in al mRNA correlates with the decreased activity of the Na,K-ATPase in uremia, under basal conditions and with the almost complete inhibition of the Na,K-ATPase, of uremic tissue by a concentration of 10-' M ouabain. Although the activity of the a2 isoform pump was not modified by uremia, the 3.4-kb message for this enzyme was increased 2.2-fold; this discrepancy is discussed. Altogether these findings demonstrate that the defective extrarenal potassium handling in uremia is at least dependent in the expression of a1 subunit of the Na,K-ATPase. (J. Clin. Invest. 1991. 88:2137-2141