clinicaltrials.gov Identifier: NCT01822795.

No abstract

This study confirms the high prevalence of MYD88 L265P mutation in PCLBCL-LT and shows its association with shorter survival. The clinical effect of MYD88 mutation activating the nuclear factor-κB pathway supports the use of targeted therapies at the time of relapse after conventional therapies.

Objective: To investigate the diagnostic value of commercially available BP230 and BP180-NC16a enzyme-linked immunosorbent assays (ELISAs) in routine practice in patients with bullous pemphigoid (BP).Design: Single-center retrospective study.Setting: French academic dermatology department. Patients:The study population comprised 138 patients, Interventions: Sera samples were analyzed by ELISA; clinical and immunopathological data were recorded from the patients' medical charts.Main Outcome Measures: BP230 and BP180-NC16a ELISA scores were evaluated with respect to clinical characteristics (number of blisters, mucosal involvement, localized or generalized disease, and outcome) and routine indirect immunofluorescence (IF).Results: Of the 138 study patients, 81 (59%) had a positive BP230 ELISA result and 119 (86%) had a positive BP180 ELISA result. There was no relationship between a positive ELISA BP230 result and the disease extent at diagnosis or the presence of mucosal involvement. Serum antibasement membrane zone autoantibodies (indirect IF) were more frequently detected when the BP230 ELISA result was positive (P Ͻ .001). The median anti-basement membrane autoantibody titer as detected by indirect IF was higher in patients with a positive BP230 result (PϽ.001). The BP180 ELISA result was associated with disease extent at diagnosis as estimated by both the percentage of patients with extensive BP (P=.01) and the mean number of blisters (P=.03) but was not associated with mucosal involvement. Conclusions:The currently available BP230 ELISA is a reliable although less-sensitive test than BP180 ELISA in BP, and its diagnostic added value compared with BP180 ELISA alone is approximately 5%. Our results support the predominant contribution of the BP230-specific autoantibodies to anti-basement membrane zone antibody titer as detected by indirect IF.

The pronounced decrease in the level of anti-BP180 autoantibodies and, to a lesser extent, those directed against BP230 confirmed the use of superpotent topical corticosteroids alone as a reference BP treatment. Furthermore, our study suggests that neurological diseases play a major role in BP, not only as a predisposing but also as a prognostic factor.

A major improvement in the survival of patients with PCDLBCL-LT has occurred over time in France, mainly as a result of the use of intensive rituximab-PCT regimens in most patients, including very elderly ones. Until further prospective clinical trials are conducted, such regimens should be considered as the standard of care in these patients.

Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment.

BackgroundDyspnea is very frequent in obese subjects. However, its assessment is complex in clinical practice. The modified Medical Research Council scale (mMRC scale) is largely used in the assessment of dyspnea in chronic respiratory diseases, but has not been validated in obesity. The objectives of this study were to evaluate the use of the mMRC scale in the assessment of dyspnea in obese subjects and to analyze its relationships with the 6-minute walk test (6MWT), lung function and biological parameters.MethodsForty-five obese subjects (17 M/28 F, BMI: 43 ± 9 kg/m2) were included in this pilot study. Dyspnea in daily living was evaluated by the mMRC scale and exertional dyspnea was evaluated by the Borg scale after 6MWT. Pulmonary function tests included spirometry, plethysmography, diffusing capacity of carbon monoxide and arterial blood gases. Fasting blood glucose, total cholesterol, triglyceride, N-terminal pro brain natriuretic peptide, C-reactive protein and hemoglobin levels were analyzed.ResultsEighty-four percent of patients had a mMRC ≥ 1 and 40% a mMRC ≥ 2. Compared to subjects with no dyspnea (mMRC = 0), a mMRC ≥ 1 was associated with a higher BMI (44 ± 9 vs 36 ± 5 kg/m2, p = 0.01), and a lower expiratory reserve volume (ERV) (50 ± 31 vs 91 ± 32%, p = 0.004), forced expiratory volume in one second (FEV1) (86 ± 17 vs 101 ± 16%, p = 0.04) and distance covered in 6MWT (401 ± 107 vs 524 ± 72 m, p = 0.007). A mMRC ≥ 2 was associated with a higher Borg score after the 6MWT (4.7 ± 2.5 vs 6.5 ± 1.5, p < 0.05).ConclusionThis study confirms that dyspnea is very frequent in obese subjects. The differences between the “dyspneic” and the “non dyspneic” groups assessed by the mMRC scale for BMI, ERV, FEV1 and distance covered in 6MWT suggests that the mMRC scale might be an useful and easy-to-use tool to assess dyspnea in daily living in obese subjects.