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Geraint P. Williams, Peter Nightingale, H. Susan Southworth, Alastair K. Denniston, Stephen Turner, John Hamburger, Simon Bowman, S. John Curnow, Saaeha Rauz; Sub-clinical Inflammation In Ocular Mucous Membrane Pemphigoid: 'Hidden' Epithelial CD45INTCD11b+CD16+CD14- Neutrophils May Predict Progression Of Conjunctival Fibrosis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1869.
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Ocular Mucous Membrane Pemphigoid (OcMMP) is a blinding autoimmune disease. Up to 50% of patients demonstrate disease progression in clinically quiescent eyes leading to sight-threatening keratopathy with no biomarkers to aid clinical decision-making. This study was designed to characterise inflammatory cells within the superficial conjunctival epithelium and define whether these could be used to detect ‘sub-clinical’ inflammation and predict progressive fibrosis.
57 patients with OcMMP underwent detailed ocular grading of disease activity and damage (including measurement of conjunctival shrinkage with fornix depth measurements), together with conjunctival ocular surface impression cytology (OSIC) at 0 and 12 months follow-up. Inflammatory cells recovered from OSIC were stained with fluorochrome-conjugated antibodies to identify leukocyte subsets by 9 colour flow cytometry. Comparisons were made with healthy age-matched (n=21) and disease controls (Primary Sjögrens Syndrome; PSS(n=19).
Conjunctival epithelial CD45INTCD11b+CD16+CD14- granulocytes were defined as neutrophils and were significantly higher (p<0.0001) amongst patients with OcMMP (109(18%)(n(%)) as compared with PSS(1.8(0.2%)) or healthy volunteers (5.8(0.8%))), and also correlated with disease activity (p<0.001). Importantly, neutrophils were significantly elevated in clinically quiescent eyes compared to healthy controls (44vs.5.8;p=0.02; 7.9vs.0.8%;p<0.001). At 12 months, 53%(37/70) eyes had clinical evidence of progression and patients with measured lower fornix shrinkage were found to have a greater number/percentage of intra-epithelial neutrophils (p<0.001). Moreover, clinically quiescent eyes were more likely to progress when accompanied by a higher proportion of neutrophils (p=0.035) and the degree of conjunctival shrinkage also increased with the number of neutrophils (p=0.04).
These data indicate an underlying conjunctival neutrophil infiltrate is present in OcMMP, even when the eye appears uninflamed. Quantification of neutrophils by OSIC/flow cytometry could represent a putative biomarker and non-invasive tool for monitoring ongoing disease activity and progression.
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