Adipokine interactions promote the pathogenesis of systemic lupus erythematosus.

BACKGROUND: Adipokines are chemical mediators released from adipose tissue involved in regulation of appetite, insulin sensitivity, immune system and inflammatory responses. Adipokines contributes to low grade inflammatory response in autoimmune disease like Systemic Lupus Erythematosus (SLE) but the pathophysiology is yet not clear. The aim of this study is to understand role of adipokine interactions in SLE disease pathogenesis. METHODS: Sixty newly diagnosed treatment naïve SLE patients fulfilling the ACR criteria and forty age-sex matched healthy subjects were enrolled in thiscase-control study. Disease activity in SLE patients was evaluated using SELENA-SLEDAI. Array of adipokines, C1q circulating immune complexes (C1q-CIC), anti-C1q, anti-ribososmal P0 (anti-RibP0) and anti-mitochondrial antibodies (AMA) levels were detected by ELISA. Antinuclear antibodies (ANA) and anti-dsDNA autoantibodieswere detected by Indirect Immunofluorescence (IIF), while antigen specificities were detected by Immunoassay blot. Serum levels of C3 and C4 complement factors were assessed by nephlometer. RESULTS: Statistically significant elevation in progranulin, adipsin and resistin levels was seen among SLE patients when compared to healthy controls (p < 0.0001). Leptin and omentin levels were significantly reduced in SLE patients (p < 0.0001). There was no statistically significant difference in serum adiponectin, chemerin and visfatin levels when these two groups were compared (p > 0.05). Adiponectin, adipsin and resistin levels were elevated in SLE patients with renal manifestations (p < 0.05). Reduced leptin levels were significantly associated with presence of renal manifestations (p < 0.05). Adiponectin levels positively correlated with disease activity (r = 0.294, p = 0.027) whereas negatively correlated with C3 levels (r = -0.439, p = 0.0007). A positive correlation was observed between hypocomplementemia and leptin levels (p < 0.05). Leptin levels were negatively correlated with disease activity, anti-dsDNA, C1q-CIC and anti-C1q levels (p < 0.05). A significant positive correlation was observed between progranulin levels and anti-ribosomal P0 antibodies (r = 0.499, p < 0.0001). CONCLUSION: Adipokines levels and associated clinical manifestations suggest involvement of adipokines in disease pathogenesis of SLE. SLE disease activity and complement components may suggest regulatory effect of adipokines (adiponectin and leptin) on disease pathogenesis. Further studies on adipokines in SLE patients with renal manifestations may propose them as prognostic markers in renal damage. TRIAL REGISTRATION: NA.

Selective IgA deficiency in autoimmune diseases.

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.

Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives.

To determine the effects of potassium supplementation on endothelial function, cardiovascular risk factors, and bone turnover and to compare potassium chloride with potassium bicarbonate, we carried out a 12-week randomized, double-blind, placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure. Urinary potassium was 77+/-16, 122+/-25, and 125+/-27 mmol/24 hours after 4 weeks on placebo, potassium chloride, and potassium bicarbonate, respectively. There were no significant differences in office blood pressure among the 3 treatment periods, and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride. Compared with placebo, both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation, increased arterial compliance as assessed by carotid-femoral pulse wave velocity, decreased left ventricular mass, and improved left ventricular diastolic function. There was no significant difference between the 2 potassium salts in these measurements. The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin:creatinine ratio, and potassium bicarbonate decreased 24-hour urinary calcium, calcium:creatinine ratio, and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly. These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system, and potassium bicarbonate may improve bone health. Importantly, these effects were found in individuals who already had a relatively low-salt and high-potassium intake.

Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives.

A reduction in salt intake lowers blood pressure. However, most previous trials were in whites with few in blacks and Asians. Salt reduction may also reduce other cardiovascular risk factors (eg, urinary albumin excretion, arterial stiffness). However, few well-controlled trials have studied these effects. We carried out a randomized double-blind crossover trial of salt restriction with slow sodium or placebo, each for 6 weeks, in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. From slow sodium to placebo, urinary sodium was reduced from 165+/-58 (+/-SD) to 110+/-49 mmol/24 hours (9.7 to 6.5 g/d salt). With this reduction in salt intake, there was a significant decrease in blood pressure from 146+/-13/91+/-8 to 141+/-12/88+/-9 mm Hg (P<0.001), urinary albumin from 10.2 (IQR: 6.8 to 18.9) to 9.1 (6.6 to 14.0) mg/24 hours (P<0.001), albumin/creatinine ratio from 0.81 (0.47 to 1.43) to 0.66 (0.44 to 1.22) mg/mmol (P<0.001), and carotid-femoral pulse wave velocity from 11.5+/-2.3 to 11.1+/-1.9 m/s (P<0.01). Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups, and the decrease in pulse wave velocity was significant in blacks only. These results demonstrate that a modest reduction in salt intake, approximately the amount of the current public health recommendations, causes significant falls in blood pressure in all 3 ethnic groups. Furthermore, it reduces urinary albumin and improves large artery compliance. Although both could be attributable to the falls in blood pressure, they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone.