Tear fluid as a source of immune biomarkers in lacrimal gland lymphomas

Adnexal lymphoma account for about 8% of extranodal lymphomas, with the lacrimal gland involved in 7–26% of cases. Lacrimal gland lymphoma (LGL) is more commonly diagnosed in older individuals, predominantly women. B-cell subtypes predominate, with MALT lymphoma being the most frequent. Diagnosis is challenging due to clinico-radiologic mimicry; therefore, analysis of tear fluid (TF) as an accessible “liquid biopsy” has practical value. Objective: to examine the profile of 7 key cytokines (IL-6, TNF-α, IL-2, IFN-γ, IL-17A, IL-4, IL-10) in TF of patients with LGL and assess their diagnostic informativeness. Methods: The pathology group included 8 patients with histologically verified LGL (mean age 56,5 ± 10,6 years; 75% women; bilateral disease – 25 %; generalized involvement–12,5%): MALT lymphoma – 5, follicular – 2, mantle cell – 1. The control group comprised 10 healthy volunteers. TF was collected in the morning during preoperative preparation, ≥50 μL (both eyes in LGL; one eye in controls). Detection frequency and concentrations of cytokines were determined by multiplex immunoassay. Results were compared between groups using statistical analysis. Results. In the affected eye of LGL patients, the detection frequency of all cytokines increased (reaching 100% for IL-6, IL-2, and IL-17A) and their levels were higher versus controls. On the contralateral, clinically healthy side, increases were evident mainly for IL-6 and IFN-γ, with a modest rise for IL-17A. Statistically significant differences from controls were observed for all cytokines on the affected side, and between sides for IL-6, TNF-α, IL-2, and IL-4 (p < 0,05). Conclusion. Profiling TF cytokines in LGL is a promising direction not only for developing noninvasive differential diagnostic tools but also for informing targeted therapeutic approaches aimed at key mechanisms of carcinogenesis, tumor growth, and progression.