Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients

International audienceINTRODUCTION: Septic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients. METHODS: This prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed. RESULTS: We observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration. CONCLUSIONS: These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease

Lymphocytopenia-associated sarcoidosis: CD4+ T-cell hypo-responsiveness to IL-2 and lectin

AbstractDespite classical identification of immune response impairment in sarcoidosis, such as anergy to delayed skin tests, the characterization of contributing mechanisms are still uncertain and infectious events complicating the course of the disease are unfrequent. Rarely, additional quantitative T-cell defects are reported in association with the disease. Although mechanisms of lymphocyte disorders are unknown, lymphocytopenia is usually revealed by an opportunistic infection.We report the case of an 18-year-old man, with pulmonary sarcoidosis, treated by corticoids, who developed cryptococcal meningitis. A CD4+ T-cell defect was simultaneously discovered, which was not influenced by corticoid arrest, persisted following infection resolution and control of sarcoidosis. In vitro experiments were performed in parallel, demonstrating a restricted CD4+ T-cell proliferation hypo-responsiveness to both IL-2 and lectin. In addition, rhIL-2 subcutaneously administrated failed to restore peripheral T-cell count.A multi-visceral sarcoidosis associated to CD4-lymphocytopenia is rarely reported and highly demonstrative of the related risk for an opportunistic infection development. In context, the absence of lectin and IL-2 effects on in vitro CD4+ T-cell proliferation assays and the inefficiency of in vivo rhIL-2 on T-cell count have been infrequently reported and suggested the presence of a defective intracellular signaling pathway, responsible for T cell defect