Natural killer cells in first-episode psychosis: an innate immune signature?

Accumulating evidence majorly implicates immune dysfunction in the etiology of psychotic disorders. In particular, altered numbers and functions of natural killer (NK) cells have been described in psychosis, but interpretation has often been confounded by a number of biases, including treatment. Eighty-one first-episode psychosis (FEP) patients who subsequently received a diagnosis of either schizophrenia (SZ; n = 30) or bipolar disorder (BP; n = 31) over a five-year follow-up period were investigated for their NK cell phenotype and compared to 61 healthy controls (HCs). We found a similar proportion of CD3-CD56+ NK cells in FEP patients and HCs. The frequency of NK cells expressing the late cell activation marker HLA-DR was significantly increased in FEP patients compared to HCs, especially in patients with BP (p < 0.0001) and, to a lesser degree, in patients with SZ (p = 0.0128). Interestingly, the expression of the activating NKG2C receptor, known to be associated with infections, was higher in patients with SZ and BP than in HCs (p < 0.0001) and correlated with HLA-DR expression, altogether defining adaptive NK cells. In terms of NK cell function, we observed a suppressed capacity of SZ-derived NK cells to mount cytotoxic responses in the presence of target cells, while NK cells from patients with BP show an inability to produce IFN-γ, a cytokine pivotal to NK function. This study strongly suggests major dysfunction of NK cells in FEP with functioning impairment correlated with psychotic, manic, and depressive symptoms in subsequently diagnosed patients with SZ and BP.

Red blood cells free α-haemoglobin pool: a biomarker to monitor the ß-thalassemia intermedia variability. The ALPHAPOOL study.

The severity of ß-thalassaemia (ß-thal) intermedia is mainly correlated to the degree of imbalanced α/non α-globin chain synthesis. The phenotypic diversity of ß-thal depends on this imbalance and reflects all possible combinations of α- and ß-globin genotypes, levels of fetal haemoglobin (HbF) and co-inheritance of other modulating factors. This study aimed to demonstrate the validity of a new surrogate of α/non α-globin biosynthetic ratio by measuring the soluble α-Hb pool in lysed red blood cells. Our results confirm that the α-Hb pool measurement allows a good discrimination between ß-thal intermedia patients, controls and α-thal patients (P < 0·003). Receiver operator characteristic analyses revealed an area under the curve of 0·978 for the α-Hb pool measurement at a threshold of 120 ng free α-Hb/mg of total Hb/ml of haemolysate (ppm) with a sensitivity and specificity of 86% and 100%, respectively, to discriminate between ß-thal and not ß-thal subjects. Significant correlations were observed between the α-Hb pool and biological parameters of ß-thal, the most significant association being observed with red cell hexokinase activity. This study indicates that the α-Hb pool could be a new marker for assistance in diagnostic orientation of ß-thal intermedia patients and may be clinically useful for monitoring the evolution of the disequilibrium of globin synthesis in response to treatments.

Impact of comorbidities on hospital-acquired infections in a geriatric rehabilitation unit: prospective study of 252 patients.

OBJECTIVES: Hospital-acquired infections (HAIs) remain a major source of morbidity and mortality in long-term care units, despite advances in antimicrobial therapy and preventive measures. Our aim was to investigate risk factors for HAIs, especially in the elderly, and to describe the relationship between comorbidities (number, severity, and specific diseases) and HAIs using a comprehensive inventory of comorbidities. DESIGN: Prospective cohort study SETTING: Geriatric rehabilitation unit in a university hospital in the Paris metropolitan area. PARTICIPANTS: Participants were 252 consecutive patients aged 75 years or older (mean age, 85 ± 6.2 years) and admitted between 2006 and 2008. MEASUREMENTS: Surveillance of HAI was conducted. A complete inventory of comorbidities was done using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Potential risk factors were evaluated in 2 risk models, one with HAI acquisition, CIRS-G, activities of daily living score less than 10, and at least 1 invasive procedure (yes/no) and the other with HAI acquisition and specific invasive procedures and diseases. RESULTS: Of the 252 patients, 97 experienced HAIs, for an incidence of 5.6 infections per 1000 bed-days. The most common HAI sites were the respiratory tract (48%; 65/136) and urinary tract (37%; 51/136). The CIRS-G global score and comorbidity index were higher in patients with than without HAIs. Among HAI categories, respiratory and urogenital diseases were more prevalent in the group with HAIs. In the model combining CIRS-G, activities of daily living score less than 10, and at least 1 invasive procedure, independent risk factors for HAI were CIRS-G index (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.13-2.11; P = .005) and invasive procedures (OR, 5.18; 95% CI, 2.77-9.71; P < .001). In the model including specific procedures and diseases, independent risk factors for HAI were intravenous catheter (OR, 7.39; 95% CI, 2.94-18.56; P < .001), urinary catheter (OR, 3.33; 95% CI, 1.40-7.88; P = .006), gastrointestinal endoscopy (OR, 3.69; 95% CI, 1.12-12.16; P = .03), pressure sores (OR, 2.52; 95% CI, 1.04-6.10; P = .03), and swallowing impairment (OR, 3.37; 95% CI, 1.16-9.74; P = .02). CONCLUSIONS: This study identified several important risk factors for HAIs. There is a need for HAI prevention via the implementation of infection-control programs, including surveillance, in rehabilitation units.