Regulatory T Cell Counts and Development of Malignancy in Patients with HIV Infection.

BACKGROUND: T-regulatory cells (Tregs) play an important role in maintaining homeostasis by attenuating the cytokine response to T-cell receptor (TCR) stimulation and by suppressing the functioning of neighboring immune cells. In Human Immunodeficiency Virus (HIV) infection, Tregs can be either beneficial, by suppressing generalized T-cell activation, or detrimental, by suppressing protective anti-HIV cell-mediated immunity. An imbalance of Tregs and effector T-cells can blunt immune responses to malignant cells or facilitate inflammation-mediated pathologies. OBJECTIVE: The purpose of our study was to explore the possible correlation between Tregs' concentration and HIV infection's parameters as well as the development of hematological and solid malignancies. METHODS: In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline. All patients were then followed up every 3 months and the development of solid or hematological malignancies was noted. RESULTS: A total of 155 patients were included in the study and the median follow-up period was 64 months. Treg counts were significantly higher among males, patients with high viral load (>350 copies/ml) and patients with virological failure to antiretroviral treatment (ART). Linear regression analysis showed a significant negative correlation between Treg levels and CD4 (+) T-cell counts. Patients with neoplasia had lower levels of Tregs while increasing levels showed a negative correlation with the development of neoplasia. CONCLUSION: In our population of HIV-infected patients, high levels of Tregs were associated with disease progression, and low baseline levels were associated with a higher probability of developing neoplasia.

Seroprevalence of hepatitis E in HIV infected patients in Greece.

HEV infection is an emerging public health problem worldwide Data concerning HEV infection in HIV+ patients in Greece is scare. The aim of the study was to determine HEV seroprevalence in patients with HIV infection in Greece. We studied 243 HIV(+) patients 214 men (88%) and 29 women (12%) with a median age of 45 years (range 19-83) who attended the HIV unit of Pathophysiology Department of Laikon General Hospital in Athens for the presence of anti-HEV IgG antibodies with (EIA) (EIA HEV IgG, Adaltis, Rome, Italy Eighteen/243 patients (7.3%) were positive for HEV IgG antibodies, a seroprevalence that was not different from that described for the blood donors group from Greece There was no difference of the presence of HbsAg, hepatitis C and hepatitis A between the HEV(+) and HEV(-) patients. There was no statistically significant difference between the HEV(+) and HEV(-) group in terms of HIV acquisition, sexual orientation, median duration of HIV infection, ART treatment, or duration of ART. Only the median age of HEV(+) was 52 years (35-78) while that of HEV(-) was 44 years (19-83)(P = 0.03). Only 2/18(11.1%) HEV(+) HIV(+) patients had abnormal ALT and AST values. The seroprevalence of hepatitis E in HIV(+) patients in Greece seems to be the same with that of the general population thus implying that HIV infection is not a risk factor for HEV infection and only age shows a positive correlation with seropositivity.

Pilot investigation of the association between serum stress neuropeptide levels and lymphocyte expression of fas and fas ligand in critical illness.

INTRODUCTION: In critical illness, apoptotic loss of immunocytes is associated with immunosuppression. AIM: To explore expression of Fas/Fas ligand (FasL) on B and T cells from critically ill patients without sepsis compared to matched controls and associations with disease severity and neuropeptide Y (NPY), cortisol, adrenocorticotropic hormone (ACTH), and prolactin (PRL) levels. METHODS: Repeated-measures correlational design with 36 critically ill patients (14-day follow-up) and 36 controls. Disease severity was assessed using the Multiple Organ Dysfunction Score (MODS) and Multi Organ Failure scale. Fas/FasL values were standardized for viable cell counts. An enzyme-linked immunosorbent assay (NPY) and electrochemiluminescence immunoassay (cortisol, ACTH, and PRL) were employed. RESULTS: Fas and FasL expression on T-helper (p < .0001-.03) and T-cytotoxic cells (p < .0001-.002) and Fas expression on B cells (p < .0001-.03) were higher in patients. MODS severity was associated with FasL expression on cytotoxic T cells (r = .752-.902, p = .023-.037). There was an inverse association between Day 1 NPY levels and Fas expression on T-helper cells (r = -.447, p = .019). On the day of maximum severity, we report for the first time an inverse association between NPY levels and FasL expression on helper (r = -.733, p = .016) and cytotoxic (r = -.862, p = .003) T cells. Cortisol levels were positively associated with counts of FasL-positive helper (r = .828) and cytotoxic (r = .544, p < .05) T cells. CONCLUSION: Results suggest a potential role for stress neuropeptides in lymphocyte survival and activation in critical illness.

Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations.

OBJECTIVE: Potential physiological correlates of stress and the role of stress neuropeptides, other than those of the hypothalamic-pituitary-adrenal axis, in critical illness have not been addressed. We investigated: (a) serum levels of stress neuropeptides (ACTH, substance P (SP), neuropeptide Y (NPY), cortisol, prolactin) in critically ill individuals compared to matched controls, (b) associations with lymphocyte counts, (c) associations among stress neuropeptide levels, and (d) associations with perceived intensity of stress, critical illness severity and survival. METHODS: Correlational design with repeated measures. Thirty-six critically ill patients were followed up for 14 days compared to 36 healthy matched controls. Stress was assessed by the ICUESS scale. Correlations, cross-sectional comparisons and multiple regression models were pursued. RESULTS: For the first time, we report lower SP (Difference of means (DM) = 2928-3286 ng/ml, p < 0.001) and NPY (DM = 0.77-0.83 ng/ml, p < 0.0001) levels in critically ill individuals compared to controls. Cortisol levels were higher (DM = 140-173 ng/ml, p<0.0001) and lymphocyte population counts (p < 0.002) were lower in patients throughout the study. NPY levels associated with lymphocyte (r = 0.411-0.664, p < 0.04), T-lymphocyte (r = 0.403-0.781, p< 0.05), T-helper (r = 0.492-0.690, p < 0.03) and T-cytotoxic cell populations (r = 0.39-0.740, p < 0.03). On day 1, cortisol levels exhibited associations with lymphocyte (r = -0.452, p = 0.01), T-cell (r = -0.446, p = 0.02), T-helper (r = -0.428, p = 0.026) and T-cytotoxic cells ( r = -0.426, p = 0.027). ACTH levels associated with NK cell counts (r = 0.326-0.441, p < 0.05). Associations among stress neuropeptides levels were observed throughout (p < 0.05). ACTH levels associated with disease severity (r = 0.340-0.387, p < 0.005). A trend for an association between ACTH levels and intensity of stress was noted (r = 0.340, p = 0.057). CONCLUSION: The significantly lowered NPY and SP levels and the associations with cortisol, ACTH and lymphocytes suggest that the role of these peptides in critical illness merit further investigation. Future studies need to address associations between these neuropeptides and functional immune cell responses and inflammatory markers in critical illness.