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Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation
  1. Srividya Gurumurthy1,
  2. Geetha Iyer, Co Correspondence2,
  3. Bhaskar Srinivasan2,
  4. Shweta Agarwal2,
  5. Narayanasamy Angayarkanni, correspondence1
  1. 1 R.S. Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Sankara Nethralaya, Chennai, India
  2. 2 C.J. Shah Cornea Services, Dr G Sitalakshmi Memorial Clinic for Ocular Disorders, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  1. Correspondence to Professor Narayanasamy Angayarkanni, R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, 41, College Road, Chennai-600 006, India; drak{at}snmail.org and Dr Geetha Iyer, C.J. Shah Cornea Services; Dr G Sitalakshmi Memorial Clinic for Ocular Disorders, Medical Research Foundation, Sankara Nethralaya, Chennai, India; drak{at}snmail.org

Abstract

Background To study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK).

Methods In a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer’s strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17). Tear cytokines were profiled using 27-bioplex array. Transforming growth factor-beta (TGF-β)-mediated extracellular matrix changes in conjunctival and oral mucosal cells were analysed by gene expression studies. 30

Results Tear cytokine profiling of chronic SJS cases at pre-MMG stage revealed significant upregulation of cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, IL-1β, monocyte chemoattractant protein-1, IL-15, IL-2, IL-17A and basic fibroblast growth factor (bFGF) with downregulation of IP-10 (interferon gamma-induced protein 10), tumour necrosis factor-α, interferon-γ, IL-10, vascular endothelial growth factor, regulated upon activation normal T-cell expressed and secreted (RANTES), IL-7, IL-12p70 and IL-13, with maximal increase in GM-CSF and maximal downregulation of IP-10, respectively. Of these, IL-2, IL-15, bFGF and IL-17A showed significant correlation with disease severity, pre-MMG. Conjunctival cells pre-MMG showed increase in TGF-β1, TGF-βRII, connective tissue growth factor and collagen-III gene expression by 10, 67, 173 and 184 folds, respectively, which dropped to 1.3, 11, 13.5 and 19 folds correspondingly, post-MMG. However, their expressions in oral mucosa were negligible.

Conclusion A proinflammatory, profibrotic, antiapoptotic ocular surface milieu characterises chronic ocular SJS. IP-10, an antifibrotic cytokine was noted to be maximally downregulated, unlike in other forms of chronic dry eye disease. The alterations in the ocular surface are seen to reverse largely with MMG for LMK.

  • Inflammation

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Footnotes

  • Contributors SG contributed to the study protocol, conducted the experiment, analysed and interpreted the data, wrote, proofed and revised the article. AN designed the study protocol, analysed and interpreted the data, wrote, proofed and revised the article. GI and BS provided materials, designed the study protocol, analysed and interpreted the data, proofed and revised the article. SA provided materials, analysed the data, proofed and revised the article.

  • Funding The study is partly funded by the Department of Science &Technology SR/WOS(A)/ LS-1221/2014(G), Government of India.

  • Competing interests None declared.

  • Patient consent An institutional consent form was signed by all patients included, agreeing to be part of the study.

  • Ethics approval Ethics Sub-Committee (Institutional Review Board) 388-2013-P.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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