Development of Gestational Age-Specific Thyroid Function Test Reference Intervals in Four Analytic Platforms Through Multilevel Modeling.

Background: A population-based reference interval (RI) of thyroid hormones in pregnancy using a standardized methodology is crucial for clinicians to make accurate diagnoses and important for the comparison of test results obtained from different analytic platforms. Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation, after exclusion of subjects with antibodies to thyroid peroxidase, thyroglobulin or thyrotropin receptor. Gestational age-specific RIs were constructed by using polynomial regression equations with MLwiN. Results: Free thyroxine (fT4) levels rose to a peak at the 7th-8th gestational weeks and then declined gradually till 28th week, while thyrotropin (TSH) level decreased from early pregnancy to a nadir at the 9th week. The data support the recent notion by the American Thyroid Association to raise the TSH upper RI to 4.0 mIU/L. We also demonstrate that thyroid hormone reference ranges are not affected in a mildly iodine-deficient population and by including women with the presence of antibodies against thyroid peroxidase and thyroglobulin who are otherwise healthy. Conclusions: The study highlights a methodology in constructing gestational age-specific thyroid function test RIs on different analytic platforms to provide a better interpretation and comparison of results obtained across different platforms.

Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity.

IL-23-dependent IL-17-producing T helper (Th) lymphocytes are associated with autoimmunity. We investigated the immunopathological mechanisms for activation of Th17 cells of patients with systemic lupus erythematosus (SLE). Concentration of cytokines/chemokine in plasma and culture supernatant from SLE patients and healthy controls were measured by ELISA or flow cytometry. Plasma IL-12, IL-17, IL-23 and CXCL10 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects (both p<0.05). Elevated IL-12, IL-17 and CXCL10 concentrations correlated positively and significantly with SLEDAI (all p<0.05). Plasma IL-12 and IL-17 showed significant and positive correlation with plasma Th1 chemokine CXCL10 concentration in SLE patients (all p<0.05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p<0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE.

Circulating bacterial-derived DNA fragment level is a strong predictor of cardiovascular disease in peritoneal dialysis patients.

BACKGROUND: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients. METHODS: We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival. RESULTS: The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 - 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005). CONCLUSIONS: Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.

Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) are transcriptional factors that play a crucial role in Th1 and Th2 development. We investigated the immunomodulatory roles of T-bet and GATA-3 and Th1/Th2 related cytokines in the pathogenesis of systemic lupus erythematosus (SLE) and their association with disease activity. METHODS: Gene expressions of T-bet, GATA-3, interferon-gamma (IFN-gamma), and interleukin 4 (IL-4) in peripheral blood mononuclear cells, and plasma concentrations of the Th1/Th2 cytokines IFN-gamma, IL-18, and IL-4, were assayed in 80 patients with SLE and 40 sex and age matched healthy subjects by real-time quantitative polymerase chain reaction and ELISA. RESULTS: The mRNA levels of T-bet and IFN-gamma and the relative expression levels of T-bet/GATA-3 and IFN-gamma/IL-4 were significantly higher, in contrast to the lower expressions of GATA-3 and IL-4, in SLE patients than controls (all p < 0.05). In all SLE patients, there were significant correlations in mRNA expression of T-bet with IFN-gamma (r = 0.590, p < 0.0001), and of GATA-3 with IL-4 (r = 0.245, p = 0.029). The relative expressions of T-bet/GATA-3 and IFN-gamma/IL-4 correlated with lupus disease activity (r = 0.229, p = 0.042; r = 0.231, p = 0.040, respectively). Plasma IL-18 concentration was increased significantly in all SLE patients (p < 0.05). The elevated plasma Th1/Th2 cytokine ratio IL-18/IL-4 correlated positively with disease activity in all SLE patients (r = 0.250, p = 0.025). CONCLUSION: There is an association between expression of Th1/Th2 transcription factors and cytokines in SLE. The elevated gene expressions of Th1/Th2 transcription factors and cytokines should provide a useful tool for assessing the functional status of T-helper lymphocytes in SLE disease development.