Interleukin-16 as a Marker of Sézary Syndrome Onset and Stage

• Published in: Journal of clinical immunology 2011-02, Vol.31 (1), p.39-50
• Main Authors: Richmond, Jillian, Tuzova, Marina, Parks, Ashley, Adams, Natalie, Martin, Elizabeth, Tawa, Marianne, Morrison, Lynne, Chaney, Keri, Kupper, Thomas S., Curiel-Lewandrowski, Clara, Cruikshank, William
• Format: Article
• Language: English
• Subjects: Aged; Biomedical and Life Sciences; Biomedicine; Dipeptidyl Peptidase 4 - metabolism; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Immunology; Infectious Diseases; Interleukin-16 - blood; Interleukin-16 - metabolism; Internal Medicine; Male; Medical Microbiology; Middle Aged; Neoplasm Staging; Prognosis; Severity of Illness Index; Sezary Syndrome - diagnosis; Sezary Syndrome - pathology; Sezary Syndrome - physiopathology; Skin Neoplasms - diagnosis; Skin Neoplasms - pathology; Skin Neoplasms - physiopathology
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-010-9464-8

Introduction Sézary syndrome is one of the most common forms of cutaneous T cell lymphoma (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.