title: Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis.
abstract: OBJECTIVE
  Ocular complications related to Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (<12 months) and chronic (>12 months) disease.
  
  
  METHODS
  Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21).
  
  
  RESULTS
  Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(-) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = -0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0).
  
  
  CONCLUSIONS
  These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression.
authors.affiliation: Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, City Hospital, Birmingham, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Geraint P
authors.initials: GP
authors.lastname: Williams
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tomlins
authors.forename: Alastair K
authors.initials: AK
authors.lastname: Denniston
authors.forename: H Susan
authors.initials: HS
authors.lastname: Southworth
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Sreekantham
authors.forename: S John
authors.initials: SJ
authors.lastname: Curnow
authors.forename: Saaeha
authors.initials: S
authors.lastname: Rauz
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D002908:Chronic Disease; D003228:Conjunctiva / Q000473:pathology*; D003229:Conjunctival Diseases / Q000276:immunology*; D003430:Cross-Sectional Studies; D004848:Epithelium / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D013262:Stevens-Johnson Syndrome / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD
keywords: SJS; TEN; innate immunity; neutrophils