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Tobino K.,Tazuke Kofukai Medical Research Institute | Tobino K.,Kitano Hospital | Muso E.,Tazuke Kofukai Medical Research Institute | Iwasaki Y.,Tazuke Kofukai Medical Research Institute | And 6 more authors.
Nephrology | Year: 2015

Aim The role of urinary (U-) thioredoxin (Trx), a class of small redox proteins, in physiological and pathological conditions, in addition to its gender specificity, has been insufficiently determined in chronic kidney disease (CKD) patients, especially in diabetes mellitus (DM) nephropathy. Methods U-Trx was measured cross-sectionally in 110 CKD outpatients with estimated glomerular filtration rate (eGFR) of >15 mL/min per 1.73 m2, namely, in 57 type 2 DM patients (male: n = 41, female: n = 16) and 53 non-DM patients (M: n = 33, F: n = 20), as well as 30 healthy controls (M: n = 11, F: n = 19). Comparisons were made among controls, DM and non-DM, and between M and F, with clinical parameters compared in each group. In addition, a comparison between average U-Trx level and the changes of renal function during a one-year period was performed. Results U-Trx was significantly higher in females than in males in controls (P < 0.05) and in non-DM patients (P < 0.05). Multiple regression analysis revealed that urinary protein (UP)/creatinine (Cr) ratio, female sex and HbA1c were independent factors affecting U-Trx among all subjects (adjusted R2 = 0.468). In DM patients, U-Trx was negatively correlated with eGFR, especially in males, and positively correlated with UP/Cr and NAG in both sexes (all P < 0.01), as well as with systolic blood pressure in all (P < 0.05). Average U-Trx was positively correlated with the rate of annual eGFR decline of male (P < 0.01) but not female DM patients. Conclusion U-Trx might have a gender-specific physiological and pathological role and be a potent marker of renal damage in DM nephropathy. Summary at a Glance This clinical study provides evidence that urine thioredoxin levels may be a biomarker of diabetic renal injury, particularly in males. © 2015 Asian Pacific Society of Nephrology.

Arimoto-Miyamoto K.,Kyoto University | Kadowaki N.,Kyoto University | Kitawaki T.,Kyoto University | Iwata S.,Tokyo Medical University | And 3 more authors.
Immunology | Year: 2010

Summary Studies in mice have shown that CD70 on dendritic cells (DCs) is sufficient to convert T-cell tolerance into immunity and hence induce anti-tumour immune responses. Therefore, it is important to investigate (i) optimal stimuli to induce CD70 on human monocyte-derived DCs (MoDCs), which are widely used for tumour immunotherapy, and (ii) the role of CD70 in functional differentiation of naive CD4+ and CD8+ T cells stimulated with MoDCs. We show that interferon-α (IFN-α) is a key cytokine to differentiate monocytes into DCs with the capacity to express CD70 upon maturation. CD70 expression on IFN-α-induced MoDCs was elicited by different categories of maturation-inducing factors (Toll-like receptor ligands, CD40 ligand and pro-inflammatory mediators), among which prostaglandin E 2 was most effective. Naive T cells stimulated with MoDCs also expressed CD70. Stimulation with MoDCs promoted naive CD4+ T cells to acquire the ability to produce T helper type 1 and 2 cytokines in a CD70-dependent manner. In contrast, the CD70-CD27 interaction diminished the production of an immunoregulatory cytokine IL-10. The CD27 signal did not play a dominant role in the induction of effector molecules in naive CD8+ T cells during the stimulation with MoDCs. This study adds a novel function to the versatile cytokines, type I IFNs, that is, the induction of CD70 on MoDCs. CD70 promotes naive CD4+ T cells to acquire immunostimulatory activity through the DC-T-cell and T-cell-T-cell interactions during the stimulation with MoDCs. Hence, the CD70-CD27 interaction may play an important role in inducing effective immune responses in DC-based immunotherapy. © 2010 Blackwell Publishing Ltd.

PubMed | Tazuke Kofukai Medical Research Institute
Type: Journal Article | Journal: Pediatric hematology and oncology | Year: 2011

Familial hemophagocytic lymphohistiocytosis (FHL), which typically has its onset during infancy, is uniformly fatal if not treated. It therefore requires prompt therapeutic intervention. Although hyperferritinemia has been emphasized as a useful marker for FHL, some nonfatal cases in infants with spontaneous remission also manifest with hyperferritinemia. However, distinguishing them is difficult because initial clinical features of these infants are similar. The authors encountered 14 infants with hyperferritinemia (serum ferritin >674 ng/mL), which normalized within 3 weeks following a benign clinical course. The authors compared the levels of HLA-DR+CD3+ T-cell subsets and interferon-gamma (IFN-) in the peripheral blood between these infants and FHL cases: one of the authors own patients and others from the literature. Serum IFN- was not detected in infants with hyperferritinemia. Moreover, levels of HLA-DR+CD3+ T cells were extremely depressed. In contrast, serum IFN- was elevated and HLA-DR+CD3+ T cells were not depressed in FHL. Measurement of activated T cells and serum IFN- might help differentiate FHL in febrile infants with transient hyperferritinemia.

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