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Presents a letter to the editor related to deleted HTLV retrovirus which may be involved in the development of cutaneous T-cell lymphomas.

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval = 4.9-7.1% vs. 3.6%, observed-to-expected drug intake ratio = 1.7; 95% confidence interval = 1.4-2.0; P < 0.0001; vildagliptin = 3.3%; 95% confidence interval = 2.5-4.1% vs. 0.7%, ratio = 4.4; 95% confidence interval = 3.5-5.7; P < 0.0001). The association of any gliptin+metformin was also higher than in the general population, ratio = 1.8 (95% confidence interval = 1.3-2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome.

Pemphigus are B-cell-mediated autoimmune diseases affecting skin and mucous membranes. They are characterized by the production of pathogenic autoantibodies directed against desmogleins (Dsg). In this prospective study, we treated 21 pemphigus patients with rituximab and analyzed immunological modifications induced by anti-CD20 immunotherapy. The total depletion of peripheral B cells led to a significant decrease of total serum IgM but not IgG levels. The B-cell depletion was followed by a progressive re-emergence of naive blood B lymphocytes, with one-third of them expressing a transitional CD19+CD38(high)CD24(high) phenotype. In most patients, clinical response to rituximab was closely related to the evolution of anti-Dsg autoantibodies that decreased in patients who achieved complete remission, whereas they remained unchanged or reincreased in relapsing patients. In contrast, serum antimicrobial IgG remained stable after rituximab treatment. B-cell repertoire analysis of three patients using immunoscope showed distortions of VH-IgM and VH-IgG immunoscope profiles before treatment, particularly clonal and oligoclonal expansions in some VH families, which were not found after B-cell reconstitution, following anti-CD20 immunotherapy. The depletion of autoreactive B cells leading to the elimination of anti-Dsg autoantibodies in most remitted patients and the restoration of a diverse B-cell repertoire by naive B lymphocytes may provide an explanation for the long-lasting efficacy of rituximab in pemphigus patients.

CD158k molecules belong to the family of killer cell immunoglobulin-like receptors (KIR) that are expressed on a minor population of circulating NK and CD8+ T lymphocytes. Here, we report a strong positive correlation between the percentage of CD158k+ blood lymphocytes analyzed by flow cytometry and the percentage of atypical circulating cells (Sezary cells) determined by cytomorphology in a large group of patients with Sezary syndrome. Moreover, we show that circulating CD4+CD158k+ lymphocytes correspond to the malignant clonal cell population. Our findings suggest that the CD158k marker could be a useful tool for the evaluation of the circulating tumoral burden and the follow-up of patients with Sezary syndrome.

The participation of BRCA1 (breast cancer 1) in DNA repair is well established, especially in mammary and ovarian cells. Our purpose was to develop a new in vivo radio-sensitizing therapy for melanoma. We therefore investigated the effect of downregulation of BRCA1 on irradiated melanoma cells using an anti-BRCA1 ribozyme. Our results show that BRCA1 downregulation increased radio-sensitivity of the A375 cell line, suggesting that BRCA1 could act as a caretaker in melanoma; however, as BRCA1 functions are not limited to maintaining genomic integrity but also regulate transcription and the cell cycle, we confirmed that the proliferative rate of BRCA1 downregulated clones did not change. We also demonstrate that: (1) among the major pro-angiogenic genes, FGF-2 was not increased before or after irradiation and vascular endothelial growth factor strongly inhibited after irradiation; (2) expression of two important metalloproteinases, matrix metalloproteinase 2 and 9, involved in melanoma metastasis were decreased before and after irradiation; (3) expression of their major inhibitor, tissue inhibitor of metalloproteinase, was mainly upregulated; and (4) that invasion of BRCA1 downregulated cells was modified. Together these data suggest that BRCA1 downregulation in melanoma cells did not make them more aggressive and could lead to new therapeutic strategies for this tumor, which is so difficult to control once metastasized.