title: Vitamin D deficiency and lower TGF-β/IL-17 ratio in a North Indian cohort of pemphigus vulgaris.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.forename: Neha
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. rwminz.minz88@gmail.com.
authors.forename: Ranjana W
authors.initials: RW
authors.lastname: Minz
authors.forename: Shashi
authors.initials: S
authors.lastname: Anand
authors.forename: Nisha V
authors.initials: NV
authors.lastname: Parmar
authors.forename: Amrinder J
authors.initials: AJ
authors.lastname: Kanwar
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014807:Vitamin D; C104450:25-hydroxyvitamin D