Introduction Sézary Syndrome is one of the most common forms of CTCL. It is characterized by skin infiltration of malignant T-cells. We examined Interleukin-16, a potent T-cell chemoattractant and cell-cycle regulator, as a prospective marker of disease onset and stage. Methods The correlation of total intracellular Interleukin-16 and surface CD26 was studied by flow cytometry. Confocal microscopy was performed to determine localization of Interleukin-16 at different stages of the disease. The levels of Interleukin-16 in plasma and culture supernatants were examined by enzyme linked immunoassay. Additionally, lymphocytes from stage IB patients were cultured in the presence of Interleukin-16 alone and in combination with Interleukin-15, and their ability to survive and proliferate was determined by cell counts and [3H]TdR incorporation. Results The data indicate that loss of both nuclear and intracellular pro-Interleukin-16 highly correspond to disease stage, with a concomitant increase in secreted mature Interleukin-16 in both culture supernatants and patients’ plasma that peaks at stage IB. Loss of intracellular Interleukin-16 strongly corresponded to loss of surface CD26, which has been shown to occur with more advanced stage of CTCL. Nuclear translocation of pro-Interleukin-16 was not observed in late stages of Sézary Syndrome, indicating this loss is not reversible. Conclusions We propose that it is feasible to use plasma levels of IL-16 as a potential diagnostic marker of Sézary Syndrome, and to use loss of intracellular IL-16 as a prognostic indicator of disease severity and stage.

Background: Eosinophilic esophagitis (EoE) is a T-cell-mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE-causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen-specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. Methods:We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E-mediated milk allergy (n = 9). We measured total and milk-specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4 + T helper (T H ) cell proliferation and cytokine production after stimulation with endotoxin-depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches.Results: Total and milk-specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused T H lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL-4 + of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects.Milk-dependent memory T H -cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL-4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy.Conclusions: Peripheral markers of allergen-specific immune activation may be useful in identifying EoE-causal foods. Assaying milk-dependent IL-4 production by circulating memory T H lymphocytes most accurately predicts clinical EoE milk allergy.

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