Abstract
Purpose :
LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is expressed during Neutrophil Extracellular Trap formation (NETosis). We have previously shown that NETs accumulate on the ocular surface of oGVHD patients, therefore, we determined whether LIGHT may serve as a biomarker for oGVHD.
Methods :
Patients who developed oGVHD after bone marrow transplant were examined and ocular surface washings (OSW) collected before treatment initiation and one month after standard of care treatment. LIGHT protein amount in the OSW was determined using a Luminex system. Correlations were estimated using Pearson correlations, and 2-tail test was done for significance.
Results :
The average LIGHT levels in tears of healthy subjects are 54.3 pg/mL. In patients with ocular GVHD, the LIGHT levels were significantly increased to 400.3 pg/mL. After initiation of treatment in oGVHD patients, LIGHT levels decreased in 66% eyes. The mean percent decrease was 67% (range = 1.5% - 99%). Concomitant OSDI data was available for 57% patients. OSDI decreased by an average of 34%. All patients in whom LIGHT levels decreased, OSDI also decreased. In 85% of these patients, OSDI reduction was clinically meaningful. Corneal staining decreased in 10 eyes out of 14 eyes in total. Corneal staining data was available for 73% eyes in which LIGHT decreased. In 71% of eyes in which LIGHT was reduced, corneal staining also decreased by an average of 41%. In 21% of eyes with LIGHT decreased, corneal staining showed no change. LIGHT decrease significantly correlated with a decrease in several other cytokines/chemokines such as: neutrophil elastase (r = 0.56, p < 0.05), oncostatin M (r = 0.76, p < 0.01), interleukin-8 (r = 0.83, p < 0.01), IP-10 ( r= 0.51, p < 0.05), extracellular DNA ( r= 0.67, p < 0.01), neutrophils in tear fluid (r = 0.53, p < 0.05). LIGHT decrease correlated with the most number of cytokines/chemokines.
Conclusions :
LIGHT protein may serve as a biomarker for following ocular graft versus host disease. It may help to optimize initiation of treatment and its intensity.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.