TNFRSF13B/TACI Mutations in Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: The pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) remains still inconclusive. Recent studies identified an increased expression of BAFF (a B cell-activating factor) and its receptor TACI (Transmembrane Activator and cAML Interactor) in nasal polyp samples, while TNFRSF13B/TACI mutations have been found in patients with benign lymphoproliferative disorders and primary antibody deficiencies. OBJECTIVE: The aim of our study was to evaluate the possible contribution of TNFRSF13B/TACI mutations in CRSwNP pathogenesis. METHODS: Forty-four (44) patients with CRSwNP (male/female: 33/11, mean age: 52.5 years, range: 16-83) were analyzed for TNFRSF13B/TACI mutations by PCR-sequencing. RESULTS: No pathogenic TNFRSF13B/TACI mutations were identified in our cohort study of CRSwNP patients. We detected two common missense mutations (p.P251L and p.V220A), along with other common silent mutations and intronic polymorphisms in an identical prevalence to healthy control population. CONCLUSION: TNFRSF13B/TACI mutations might not play a role in the pathogenesis of CRSwNP.

Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension.

BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.

Pulmonary function and circulating adhesion molecules in patients with diabetes mellitus.

BACKGROUND: Lung function in diabetes has been reported in several studies with contradictory results. Diabetes mellitus increases expression of adhesion molecules through hyperglycemia. These molecules play an important role in the pathophysiological dysfunction of the vasculature. OBJECTIVE: To explore the possible relationship between lung function and circulating levels of adhesion molecules in diabetes. METHODS: Sixteen type 1 diabetic patients, 33 type 2 diabetic patients and 22 healthy subjects matched for age and sex were studied. Spirometry measurements were performed and pulmonary diffusion capacity for carbon monoxide (DLco) was measured in sitting and supine positions by the single-breath method corrected by alveolar volume (VA). Glycosylated hemoglobin, retinopathy and nephropathy were included as parameters of metabolic control and diabetic complications. Circulating levels of soluble E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were determined in all subjects. RESULTS: Diabetic subjects showed lower variation in DLco and DLco/VA by changing posture from sitting to supine position (P=0.043 and P<0.001, respectively), and showed reduced total lung capacity (P<0.001) and forced expiratory volume in 1 s/forced vital capacity (P=0.009) compared with healthy control subjects. Serum concentrations of E-selectin were elevated in diabetic patients (P<0.001). There was no difference in serum VCAM-1 concentrations between diabetic and control subjects. On stepwise regression analysis, E-selectin concentrations were the most important contributing factor to the variation in DLco/VA. CONCLUSIONS: Diabetic patients show lower pulmonary volumes and variation in DLco by changing posture from sitting to supine position, and they also show increased levels of E-selectin. A possible explanation is impaired pulmonary microvasculature, because adhesion molecules seem to be sensitive markers of endothelial activation and damage seen in diabetes.