Vitamin D deficiency and lower TGF-β/IL-17 ratio in a North Indian cohort of pemphigus vulgaris.
Vitamin D deficiency and lower TGF-β/IL-17 ratio in a North Indian cohort of pemphigus vulgaris.
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DOI：
10.1186/1756-0500-7-536
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发表时间：
2014-08-15
影响因子：
1.8
通讯作者：
Kanwar AJ
中科院分区：
文献类型：
--
作者：
Joshi N;Minz RW;Anand S;Parmar NV;Kanwar AJ
寻常天疱疮（PV）是一种自身免疫性大疱性疾病，由致病性桥粒芯蛋白-3自身抗体引起的角质形成细胞棘层松解引起。由于维生素D对先天性和适应性免疫应答的免疫调节作用，维生素D的作用最近已涉及各种自身免疫性疾病。维生素D免疫调节的关键机制之一是通过抑制Th 17功能发挥抗炎作用。因此，维生素D可能参与PV的发病机制。在这项研究中，PV患者以及健康对照者的血清维生素D、IL-17和TGF-β水平被估计，以了解参与疾病发病机制的潜在免疫机制。这项回顾性研究包括30例经活检证实的PV患者的血清。招募10名年龄匹配的无任何皮肤或自身免疫性疾病的志愿者作为健康对照（HC）。使用化学发光法测定血清维生素D水平，而使用ELISA法测定IL-17和TGF-β水平。所有患者均显示维生素D水平不足（11.1 ± 5.8 ng/ml）。此外，所有PV患者血清IL-17水平均升高（210.7 ± 105.3），而在任何（n = 10）健康对照血清中均未检测到IL-17（ELISA灵敏度≥ 8 pg/ml）。与健康对照相比，患者血清中的平均血清TGF-β浓度也较低，并且与健康对照（1363.34 ± 559.52）相比，患者中的TGF-β/IL-17比率（30.30 ± 28）显著降低。维生素缺乏症在印度北部很常见，通过健康对照组的维生素缺乏水平可以确定，并且在PV患者中也一直观察到。这些低水平与年龄或性别无关。PV患者血清IL-17水平升高，TGF-β/IL-17比值显著降低，提示T效应细胞Treg/Th-17轴失调可能在PV发病机制中具有重要意义。因此，该研究表明，维生素D不足可能是PV的一个诱发因素，通过其在体内调节T细胞功能的各种适应性免疫机制中的作用而发挥作用。因此，需要进一步评估Treg/Th-17轴，因为它可能在疾病进展中起重要作用。
Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by acantholysis of keratinocytes due to pathogenic desmoglein-3 autoantibodies. Role of vitamin D has been recently implicated in various autoimmune conditions due to its immunomodulatory effects on innate and adaptive immune responses. One of the key mechanisms of the immune regulation by vitamin D is through its anti-inflammatory effects by suppression of Th17 functions. Thus, vitamin D may be involved in pathogenesis of PV. In this study, the serum vitamin D, IL-17 and TGF-β levels in PV patients as well as healthy controls were estimated in order to understand the underlying immune mechanism involved in disease pathogenesis. This retrospective study included 30 biopsy proven PV patients’ sera. Ten age matched volunteers without any cutaneous or autoimmune conditions were recruited as healthy control (HC). Serum Vitamin D levels were measured using chemiluminescence, whereas IL-17 and TGF-β levels were determined using ELISA. All patients showed deficient vitamin D levels (11.1 ± 5.8 ng/ml). Moreover, all the PV patients had elevated serum IL-17 levels (210.7 ± 105.3), whereas it was not detectable in any (n = 10) of the healthy controls sera (ELISA sensitivity ≥ 8 pg/ml). The mean serum TGF-β concentration was also lower in patient sera as compared to healthy control, and the TGF-β/IL-17 ratio was drastically reduced in patients (30.30 ± 28), as compared to healthy controls (1363.34 ± 559.52). Hypovitaminosis is common in North India, as ascertained by deficient levels in healthy controls, and was also consistently observed in PV patient. These low levels were not related to age or gender. The increased serum IL-17 and dramatic reduction in TGF-β/IL-17 ratio in diseased patients further indicate that dysregulation of the Treg/Th-17 axis of T effector cells may be of significance in pathogenesis of PV. Thus, the study indicates that vitamin D insufficiency may be a predisposing factor in PV, contributing through its role in any of the various adaptive immune mechanisms that regulate T cell functions in vivo. Thus, there is a need to further evaluate the Treg/Th-17 axis, as it may have an important role in disease progression.