Unraveling the role of the vitamin D-VDR pathway in pemphigus vulgaris from Tunisian patients.

Vitamin D dysregulation has been recognized as a factor that may cause or aggravate autoimmunity. Vitamin D deficiency was found to be common in pemphigus vulgaris (PV) in different populations. This study aimed to investigate the vitamin D-VDR pathway in PV in the Tunisian population. A serological study was carried out to determine the vitamin D status in newly diagnosed PV patients. CYP27B1, CYP24A1 and VDR mRNA expression was assessed using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) from untreated newly diagnosed and treated PV patients. In addition, a genetic study was accomplished on VDR polymorphisms to investigate the changes in VDR gene expression. Overall, the serological study confirmed the hypovitaminosis D in newly diagnosed PV patients. Vitamin D-VDR pathway gene expression showed downregulation of CYP27B1 and CYP24A1 mRNA in first-discovery patients compared to healthy controls, while VDR mRNA was highly expressed in newly diagnosed PV patients. Moreover, CYP27B1, CYP24A1 and VDR mRNA were significantly upregulated in chronic disease severity groups compared to mild disease groups. The genetic study showed low VDR gene expression in carriers of FokI > CC genotype, which was more frequent among PV patients, and FokI > C-TaqI > C-ApaI > A-polyA > A16 haplotype, suggesting that the VDR gene polymorphisms testing can provide useful information for PV treatment decision-making. In conclusion, our findings underline the impact of vitamin D-VDR pathway disruption in the PV pathophysiology in Tunisian patients.

Annexin A1 and its receptor gene polymorphisms in systemic lupus erythematosus in the Tunisian population.

BACKGROUND: An association between ANXA1, FPR1 and FPR2 gene polymorphisms and the patho-physiology of many human diseases was suggested by numerous studies. OBJECTIVE: Our study aimed to evaluate association between common polymorphisms in the 9q21.13 and 19q13.41 and susceptibility to systemic lupus erythematosus (SLE) in the Tunisian population. MATERIALS: We performed a case-control study on 107 Tunisian SLE patients and 122 healthy controls to explore 9 polymorphisms of the three studied genes: rs2811226 and rs3739959 (ANXA1), rs5030880, rs1042229, rs1461765570, rs17849971, rs867228 (FPR1), rs17694990 and rs11666254 (FPR2). RESULTS: Four polymorphisms were found to be linked with SLE susceptibility: rs3739959-ANXA1 > G and GG (p = 0.021, OR = 1.73 and p = 0.014, OR = 2.06 respectively), rs867228-FPR1 > TT (p = 0.014, OR = 4.59), rs11666254-FPR2 > GG (p = 0.019, OR = 8.34) and rs17694990-FPR2 > T (p = 0.05, OR = 1.506). In homogenous groups of SLE patients depending on clinical manifestations and serological results, previous associations were confirmed with a panoply of manifestations of lupus including lupus nephritis, malar rash, mouth ulceration and hypocomplementia. CONCLUSION: Our study showed an association between ANXA1 > rs3739959, FPR1 > rs867228, FPR2 > rs11666254, FPR2 > rs17694990 and SLE susceptibility. Our results also showed a strong association between the two ANXA1 studied SNPs and LN which allowed us to suggest these two SNPs as biomarkers of LN development in SLE. Further research is needed to understand by which mechanism the gene variants affect susceptibility to SLE. Key Points • Lupus erythematosus is an autoimmune disease in which a panoply of factors are implicated • Annexin A1 interaction with its receptors are suggested as a target in therapy of a panoply of human disease in particular cancers • The present results highlighted the implication of Annexin A1 and its receptors gene polymorphisms in the physiopathology of lupus, in particular in the involvement of renal and cutaneous lesions.