Atypical patterns of STAT3 phosphorylation in subpopulations B cells in patients with common variable immunodeficiency.

BACKGROUND: Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by defective B cell differentiation and antibody production. Interleukin (IL)-21 activates STAT3, a potent regulator of B cell differentiation into plasma cells. We have studied the phosphorylation of STAT3 in CVID patients and its contribution to B cells subsets. METHODS: We studied 23 CVID patients and 14 healthy donors (HD), determining pSTAT3 in naïve and memory B cells, stimulated with IL-21 at 15 and 60 min. RESULTS: pSTAT3 was increased in total (p = 0.044), naïve (p = 0.023), and memory (p = 0.001) B cells at 60 min in CVID patients compared with HD. We classified patients by the percentage of isotype-switched memory B cells. We observed an increase in pSTAT3 at 60 min in memory B cells in both CVID groups of patients (p = 0.026, p = 0.007, respectively). Interestingly, the analysis of each group individually; demonstrated that patients with decreased memory B cells exhibited an increase in pSTAT3 at 60 min (p = 0.023), while HD had an expected decrease in pSTAT3 (p = 0.045). CONCLUSION: CVID patients showed an increased atypical of pSTAT3, which could affect the differentiation of B cells. Further studies in the IL-21 pathway are necessary to understand how this alteration could promote differentiation defects in patient B cells.

Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma.

Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.

Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma

Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.