Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR-RFLP technique was used to detect IL10 promoter genotypes at the positions of −1082 (G/A), −819 (C/T) and −592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of −1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21-5.82), p-value = 0.046]. The CC genotype in −819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26-9.07), p-value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15-3.01), p-value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of −592 SNP and decreased in AA genotype carriers of −1082. IL10 was also increased in SLE patients with CGT (−592/−1082/−819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of −592 and TT genotype carriers at the region of −819. SLEDAI was also elevated among patients with CGC (−592/−1082/−819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 -819(C/T), −1082(G/A) and −592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings. K E Y W O R D S haplotype, interleukin 10, polymorphism, promoter, systemic lupus erythematosus | 21 MOHAMMADI et Al.

Background and Objectives: Vitamin D is an essential secosteroid that plays a crucial role in the homeostasis of a few mineral elements, particularly calcium. Since vitamin D deficiency and thyroid diseases are two important global health problems, we aimed to investigate a possible relationship of vitamin D and calcium levels with hypothyroidism in an Iranian population.Methods: This case-control study was conducted on 175 subjects with hypothyroidism (75 males and 100 females) and 175 euthyroid controls (85 males and 90 females) who were referred to a laboratory in Gorgan, Iran. Serum levels of 25hydroxyvitamin D, calcium, thyroid-stimulating hormone (TSH), free triiodothyronine (free T3) and thyroxine (total T4) were measured in all participants.Results: Vitamin D and calcium were significantly lower in patients with hypothyroidism (P<0.0001). Free T3 and calcium levels differed significantly among hypothyroid patients based on their vitamin D status (P<0.0001), but vitamin D levels were within sufficient range in all groups. Moreover, there was a positive correlation between free T3 with vitamin D (r= 0.337, P<0.0001) and calcium (r= 0.361, P<0.0001) levels.Conclusions: Our results suggest that there may be a relationship between decreased vitamin D levels and thyroid function parameters.

Background: Cytokines, as key regulators of immune responses, are imbalanced in tuberculosis (TB) which may reflect the status of the disease. Therefore, cytokines could be introduced as potential diagnostic and prognostic TB biomarkers. Objectives: Here, we examined the plasma levels of IL-17, IL-6, and TGF-β among newly diagnosed patients with TB in comparison to normal subjects and analyzed the diagnostic utility of each cytokine to introduce a novel TB biomarker. Methods: A total of 105 smear-positive, including 78 newly diagnosed (ND) and 27 under treatment (UT) patients with pulmonary TB and 111 age-and sex-matched healthy subjects were recruited. ELISA cytokine assay was used to determine the plasma levels of IL-17, IL-6, and TGF-β. Results: IL-6 plasma level was higher in the ND patients than healthy subjects (P = 0.002) and the UT patients (P < 0.0001). Also, IL-17 and TGF-β were significantly overexpressed among both groups of patients with TB compared with healthy subjects. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic utility of the evaluated cytokines. Area under the curve (AUC) for IL-6 was 0.5598 (P = 0.129). Regarding the diagnostic value of IL-6 to distinguish between the ND and UT patients, AUC for IL-6 was 0.8139 (P < 0.0001). Setting the optimal cut-off value at 23.75 gave a sensitivity of 77.78% and a specificity of 74.36%. AUC for IL-17 was 0.9148 (P < 0.0001), while AUC for TGF-β was 0.8877 (P < 0.0001). Setting the optimal cut-off value at 14.05 for IL-17 gave a sensitivity of 81.90% and a specificity of 79.28%, while setting the optimal cut-off value at 51.20 for TGF-β resulted in a sensitivity of 82.69% and a specificity of 72.73%. Conclusions: All evaluated cytokines were overexpressed in newly diagnosed TB patients with different diagnostic utilities. IL-6 is more convenient in distinguishing the ND from UT patients. IL-17 is more specific in distinguishing TB infection and TGF-β represented a higher sensitivity. It is suggested that multiple cytokine assay should be conducted to have a better diagnostic performance rather than individual cytokine evaluation.