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Sapna Tibrewal, Joy Sarkar, Sarmad Hassan Jassim, Yair Ivanir, Eunjae Kim, Yong Soo Byun, Rama Wahood, Shweta Chaudhary, Kaele Leonard, Sandeep Jain; Non-self extracellular DNA (eDNA) may potentiate inflammation and severity of dry eyes in patients with chronic ocular Graft-Versus-Host Disease (GVHD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2008.
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We hypothesize that donor neutrophil-derived non-self eDNA present on the ocular surface of patients with chronic ocular GVHD promotes inflammation and severity of dry eye.
We examined patients with severe dry eye disease (Schirmer I ≤ 2 mm) and compared the clinical signs and symptoms between GVHD (n=12) and Non-GVHD (n=12) dry eye patients. Fluorescent in situ hybridization (FISH) was performed to identify the sex chromosomes in mucoid films seen on the ocular surface of these patients. One-way Mixed Lymphocyte Reaction (MLR) was performed using stimulator cells (irradiated C57BL/6 mouse splenocytes) and responder cells (BALB/c mouse splenocytes) to evaluate differences in immunogenic potential of allogeneic (C57BL/6 mouse) and syngeneic (BALB /c mouse) DNA. Cell-cytotoxicity experiments were performed using two different human corneal epithelial cell lines (Human corneal epithelial Large T antigen; HCET, and Human corneolimbal epithelial; HCLE) to compare the effect of allogeneic (HCLE) and syngeneic (HCET) DNA on cell viability, cytotoxicity and cellular apoptosis.
GVHD patients were more symptomatic than Non-GVHD dry eye patients with similar tear deficiency (Schirmer I = 0.5±0.2 and 0.7±0.2 mm, respectively, p=0.16; OSDI score = 54.7±4.6 and 41.8±3.8, respectively, p<0.05). Mucoid films from ocular surface of GVHD patients contained abundant neutrophil extracellular traps (NETs). FISH examination revealed that eDNA within these NETs was non-self. Syngeneic and allogeneic DNA did not produce cytotoxicity, cell viability, or apoptosis in HCET cells, however allogeneic DNA was significantly more immunostimulatory than syngeneic DNA in MLR.
Patients with chronic GVHD have non-self eDNA on the ocular surface, which has greater immunostimulatory potential than self DNA. This may be one reason for greater severity of dry eye disease in these patients.
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