Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients.

Background: The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4+T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance. Methods: CD4+T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers. CD4+T cells from the 3 groups were compared in terms of their gene expression profile, phenotype and functionally upon activation. Results: Gene expression analysis of transcription factors and signalling proteins, in addition to surface proteins expression and cytokine production, revealed that tolerant recipients possessed fewer Th17 cells and exhibited reduced Th17 responses, relative to patients with chronic rejection or healthy volunteers. Furthermore, impaired TCR signalling and altered cytokine cooperation by monocytes contributed to the development of Th17 cells in tolerant recipients. Conclusions: These data suggest that defective proinflammatory Th17 responses may contribute to the prolonged graft survival and stable graft function, which is observed in tolerant recipients in the absence of immunosuppressive agents. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Subcutaneous Islet Allotransplantation Without Immunosuppression Therapy: the Dream of the Diabetologists and of their Patients.

No abstract available

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mTOR Inhibition for Transplantation: More may not be better.

No abstract available

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Urinary CXCL10 chemokine is associated with alloimmune and virus compartment-specific renal allograft inflammation.

Background: Urinary CXCL10 is a promising biomarker for subclinical tubulointerstitial inflammation, but limited data exists regarding its correlation with (micro)vascular inflammation. Furthermore, no study has evaluated whether concomitant serum CXCL10 improves the discrimination for (micro)vascular inflammation. Methods: We investigated whether serum/urinary CXCL10 reflect subclinical inflammation within different renal compartments. Patients (n=107) with 107 surveillance biopsies were classified as: normal histology (n=47), normal histology with BKV or CMV viremia (n=17), moderate-severe tubulointerstitial inflammation (tubulitis >=2, n=18), pure microvascular inflammation (n=15), and isolated v lesions (n=10). Serum and urinary CXCL10 ELISA was performed. An independent validation set was evaluated for urine CXCL10: normal histology (n=14), normal histology with BKV or CMV viremia (n=19), tubulitis >=2 (n=15), pure microvascular inflammation (n=41), and isolated v lesions (n=14). Results: Elevated urinary CXCL10 reflected inflammation within the tubulointerstitial (urinary CXCL10/creatinine 1.23ng/mmol vs. 0.46ng/mmol, p=0.02; AUC 0.69, p=0.001) and microvascular compartments (urinary CXCL10/creatinine 1.72ng/mmol vs. 0.46ng/mmol, p=0.03; AUC 0.69, p=0.02) compared to normal histology. Intriguingly, urinary CXCL10 was predominantly elevated with peritubular capillaritis, but not glomerulitis (p=0.04). Furthermore, urinary CXCL10 corresponded with BKV, but not CMV viremia (p=0.02). These urine CXCL10 findings were confirmed in the independent validation set. Finally, serum CXCL10 was elevated with BKV and CMV viremia but was not associated with microvascular or vascular inflammation (p>=0.19). Conclusions: Urinary CXCL10 reflects subclinical inflammation within the tubulointerstitial and peritubular capillary spaces, but not the vascular/systemic compartments; this was consistent with BKV (tubulointerstitial) and CMV viremia (systemic). Serum CXCL10 was not a useful marker for (micro)vascular inflammation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Evaluation of the efficacy and safety of oral isotretinoin versus topical isotretinoin in the treatment of plane warts: a randomized open trial

Abstract

Background

Plane warts are a common therapeutic problem. Our aim was to assess the efficacy and safety of oral versus topical isotretinoin in the treatment of plane warts.

Methods

Forty patients with multiple plane warts were randomized into two groups. Group A was treated with oral isotretinoin capsules in the dose of 0.5 mg/kg/d and Group B with topical isotretinoin 0.05% in gel formulation once daily at night. Treatment was given to the patients for 3 months or until the complete clearance of lesions, whichever was earlier. Patients with complete response were followed up monthly for 4 months to record the relapse rate.

Results

Results were analyzed in 16 patients of Group A and 13 patients of Group B. At the end of 3 months of therapy, 11 (69%) patients in Group A had complete remission whereas five (31%) had partial remission. In Group B, at the end of study, five (38%) patients had complete remission and six (46%) had partial remission, whereas two patients had no remission. The difference was statistically significant between two groups; P < 0.0001. The most common side effect in Group A was cheilitis. In Group B, five patients had to be dropped because they developed severe erythema and scaling.

Conclusion

Oral isotretinoin showed better and earlier response than topical isotretinoin. Oral isotretinoin should definitely be given a trial particularly in cases of multiple facial warts before trying various destructive procedures.

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Issue Information - Contents

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Cover Image

The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.

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