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Jing-Feng Huang, Yi Zhang, Jim Li, Kay D. Rittenhouse; Molecular Bases for Multiple Subgroups of Dry Eye Patients?. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2317.
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Identification and characterization of the underlying molecular and cellular components contributing to the heterogeneity of ocular surface disease pathology and manifestation is of significant interest. In this study, we characterized patients with ocular surface disease at molecular level by tear protein marker profiling.
We prospectively, in two investigator sites, recruited 22 asymptomatic control subjects and 80 patients with ocular surface disease symptoms and different levels of corneal fluorescein staining (CS) (NEI scale). Of these patients, 30 had CS score < 4; 29 had CS between 4 to 7; and 21 had CS greater than 7. At study visits, tear fluids were collected from each eye with microcapillary tubes for a systematic analysis of 43 protein markers of immune mediators or markers with potential immunopathological relevance using micro-beads based multiplexed immunoassay. In addition, symptoms and clinical objective signs of dry eye disease were evaluated to assess disease characteristics.
Association analysis among tear markers showed strong correlation between certain cytokines and immune mediators. For example, the following pairs of markers were found to have partial correlation coefficient greater than 0.80: IL-17 vs. IL-23, IL-23 vs. IL-12p70, IL-1b vs. IL-17, IL-1b vs. IL-12p70, and Complement 3 vs. IgA. The expression profiles of the tear markers further revealed significant heterogeneity among patients. 3 - 4 subgroups of patients were identified and each displayed differential levels of tear markers. Subgroup A patients were found to have significantly higher level of T cell and related cytokines, such as IL-17 and IL-23, than control group and other patient subgroups (P < 0.05); while subgroup B patients had significantly higher level of IL-8 than control group and other patient subgroups (P<0.05), but had lower level of IL-17 than control group and subgroup A patients (P<0.05). Subgroup B patients were found to have significantly higher level of CS and conjunctival staining than other subgroups of patients (P<0.05).
In this study, we identify, for the first time, multiple subgroups of patients based on the profiles of tear protein markers. Different subgroups of patients are segregated by distinct molecular components of immune activation, implicating different immunopathological mechanisms involved in patients with ocular surface disease. Further analysis of the profiles of tear protein markers and disease characteristics of different subgroups will be presented, and implication of the finding will be discussed.
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