PurposeWe investigated whether C-reactive protein (CRP) to serum albumin ratio (CAR) could be an independent predictor of all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Materials and MethodsWe retrospectively reviewed the medical records of 170 patients with AAV. We collected clinical and laboratory data. We also examined AAV-related and traditional risk factors of all-cause mortality. To assess the hazard ratios of variables, we performed univariable and multivariable Cox hazard model analyses.ResultsThe mean age was 55.0 years and 53 patients (31.2%) were male among 170 patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was detected in 129 patients (75.9%). The initial mean CRP and serum albumin were 41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most common risk factor of mortality was hypertension (42.4%), followed by chronic kidney disease ≥stage 3 (25.9%). Fourteen patients (8.2%) died during the mean follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at diagnosis was identified as an independent predictor of all-cause of mortality comparable to diabetes mellitus (DM). Moreover, patients with CAR ≥10.35 and having DM exhibited a higher frequency of all-cause mortality than those without.ConclusionCAR at diagnosis can be an independent predictor of all-cause mortality, comparable to DM, the conventional risk factor of mortality.

Significance T H 17 cells are a subset of CD4 + T helper cells that secrete the cytokine IL-17 and play a role in autoimmunity. RORγt is identified as a key transcription factor driving the T H 17 differentiation. Sequence analysis indicated that transcription factor contains several conserved DNA-binding domain and isotype-specific domain that we termed transcription modulation domain (TMD). We designed a novel therapeutics, tRORγt-TMD, to deliver RORγt-TMD efficiently into the nucleus of the cells that regulates T H 17 cell functions and T H 17-mediated autoimmune diseases. With the same concept, tTbet-TMD also can regulate T H 1 functions. In conclusion, tRORγt-TMD/tTbet-TMD can be novel and highly specific therapeutics for the treatment of T H 17/T H 1-mediated inflammatory disease and further allows us to discover new function of RORγt/Tbet in animals without genetic alteration.

We investigated the rate of rheumatoid factor (RF) false positivity at diagnosis and its influence on clinical and prognostic features and rheumatoid arthritis (RA) development during the follow-up in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients without RA or other medical conditions triggering RF false positivity. We reviewed the medical records of 128 AAV patients. We divided patients with AAV and each variant into two groups according to RF positivity and compared variables between the two groups. Odds ratio and cumulative relapse-free survival rate were obtained by multivariate logistic regression analysis and the Kaplan-Meier survival analysis, respectively. The mean age at diagnosis was 53.6 years and 41 patients were male. Of 128 AAV patients, 69 patients (53.9%) were classified as microscopic polyangiitis (MPA), 29 (22.7%) as granulomatosis with polyangiitis (GPA) and 30 (23.4%) as eosinophilic GPA (EGPA). The rate of RF false positivity was 39.1% in AAV patients. On univariate analysis, general, cutaneous and mucous and ocular manifestations and myeloperoxidase (MPO)-ANCA (or perinuclear (P)-ANCA) positivity were associated with RF false positivity in patients with AAV. On multivariate analysis, cutaneous manifestation was the only independent predictor of RF false positivity in EGPA patients. RF false positivity had no influence on cumulative relapse-free survival rate of AAV or RA development during the follow-up. RF false positivity rate was 39.1% in AAV patients and it was associated with cutaneous manifestation in EGPA patients at diagnosis, but not relapses of AAV or RA development during the follow-up.

Hypoxia-inducible factor-1 alpha (HIF1A) is an important transcription factor for angiogenesis. Recent studies have used the protein transduction domain (PTD) to deliver genes, but the PTD has not been used to induce the expression of HIF1A. This study aimed at using a novel PTD (Hph-1-GAL4; ARVRRRGPRR) to overexpress the HIF1A and identify the effects on angiogenesis in vitro and in vivo. Overexpression of HIF1A was induced using Hph-1-GAL4 in human umbilical vein/vascular endothelium cells (HUVEC). The expression levels of genes were analyzed by the quantitative real-time polymerase chain reaction (qPCR) after 2 and 4 days, respectively. An in vitro tube formation was performed using Diff-Quik staining. HIF1A and Hph-1-GAL4 were injected subcutaneously into the ventral area of each 5-week-old mouse. All of the plugs were retrieved after 1 week, and the gene expression levels were evaluated by qPCR. Each Matrigel plug was evaluated using the hemoglobin assay and hematoxylin and eosin (HE) staining. The expression levels of HIF1A and HIF1A target genes were significantly higher in HIF1A-transfected HUVEC than in control HUVEC in vitro. In the in vivo Matrigel plug assay, the amount of hemoglobin was significantly higher in the HIF1A-treatment group than in the PBS-treatment group. Blood vessels were identified in the HIF1A-treatment group. The expression levels of HIF1A, vascular endothelial growth factor (Vegf), and Cd31 were significantly higher in the HIF1A-treatment group than in the PBS-treatment group. These findings suggest that using Hph-1-G4D to overexpress HIF1A might be useful for transferring genes and regenerating tissues.

No abstract