[The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance].

Objective: To evaluate the expression and clinical significance of γ-glutamylcyclotransferase (GGCT) in patients with bladder urothelial cell carcinoma. Methods: Immunohistochemical staining for GGCT were performed on tissue sections of 86 patients with bladder urothelial cell carcinoma and 10 normal controls, and the correlations between GGCT and clinicopathological characteristics and the prognosis were analyzed. Results: The positive rate of the expression of GGCT in 86 cases of bladder urothelial cell carcinoma was 61.6% (53/86). GGCT protein was located mainly in cancer cell cytoplasm, and it can be seen in the nucleus of the tumor cells in some cases. The level of GGCT expression was positively related to pathological classification (P<0.001), stage (P=0.020), and tumor size (P=0.025). Immunohistochemical semiquantitative analysis showed that the expression of GGCT in patients with T1 stage of non-muscle invasion bladder urothelial cell carcinoma was significantly higher than that with Ta stage (P=0.034). Kaplan-Meier analysis showed that the expression of GGCT was correlated with the recurrence-free survival in patients with non-muscle invasive bladder cancer, the recurrence-free survival rate was lower in the GGCT positive group (P=0.029). Multivariate COX regression analysis showed that the pathological stage (OR=5.029, P=0.009) and the number of tumors (OR=3.320, P=0.024)were the independent risk factors for recurrence-free survival in patients with early urothelial cell carcinoma of the bladder. Conclusions: The expression of GGCT is significantly increased in bladder urothelial cell carcinoma and is related to the malignant biological behavior and progression of tumor. Patients with GGCT positive early bladder tumor are inclined to recur.

Diagnosis and risk stratification in patients with anti-RNP autoimmunity.

INTRODUCTION: Anti-RNP autoantibodies occur either in mixed connective tissue disease (MCTD) (with a frequently favorable prognosis), or in systemic lupus erythematosus (SLE) cases with aggressive major organ disease. It is uncertain how to assess for the risk of severe disease in anti-RNP + patients. METHODS: Following institutional review board-approved protocols, clinical data and blood were collected from patients with known or suspected anti-RNP autoimmunity and normal controls in a cohort study. Samples were screened for parameters of immune activation. Groups were compared based on clinical diagnoses, disease classification criteria, disease activity and specific end-organ clinical manifestations. RESULTS: Ninety-seven per cent of patients satisfying Alarcon-Segovia MCTD criteria also met Systemic Lupus International Collaborating Clinic (SLICC) SLE criteria, while 47% of the anti-RNP + SLE patients also met MCTD criteria. Among SLICC SLE patients, MCTD criteria were associated with reduced rates of renal disease (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.3-14.0), increased rates of Raynaud's phenomenon (OR 3.5, 95% CI 1.3-9.5) and increased serum B-cell maturation antigen, transmembrane activator and CAML interactor and TNFα levels. Circulating immune markers and markers of type I interferon activation were not effective at distinguishing clinical subgroups. CONCLUSIONS: Among anti-RNP patients, the question of MCTD versus SLE is not either/or: most MCTD patients also have lupus. MCTD classification criteria (but not a broad set of immune markers) distinguish a subset of SLE patients at reduced risk for renal disease.

Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein-protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.