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Episodic angioedema with eosinophilia (EAE) (Gleich syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia, and frequent elevated serum IgM level. We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. A total of 30 patients with a median age at diagnosis of 41 years (range, 5-84) were included. The median duration of each crisis was 5.5 days (range, 1-90), with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%), of whom 5 (17%) showed evidence of clonal T-cell receptor gamma locus gene (TRG) rearrangement. The median duration of follow-up was 53 months (range, 31-99). The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio, 4.15; 95% confidence interval, 1.18-14.66; P =.02). At last follow-up, 3 patients (10%) were able to have all treatments withdrawn and 11 (37%) were in clinical and biologic remission with less than 10 mg of prednisone daily. EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) antibodies constitute a new generation of cancer treatments, associated with immune-related adverse events (irAEs). A previous retrospective study of patients with metastatic melanoma (treated mostly with anti-CTLA4 antibodies) reported a serious infection rate of 7.3%. The main risk factors were corticoids and infliximab use. We sought to describe infections and risk factors among patients receiving anti–PD-1/PD-L1 ICIs. We reviewed 200 medical records sampled randomly from a French prospective registry, which collates patients treated with anti–PD-1/PD-L1 ICIs. We recorded demographic data, the occurrence of irAEs, immunosuppressant use, and the outcome. Thirty-six patients (18%) experienced an infection by a median (interquartile range) of 47 (19.2–132) days after initiation of the ICI. Twenty-one patients (58.3%) had a lung infection, seven (19.4%) had a skin infection, seven (19.4%) had a urinary tract infection, and all of them received antibiotics. The infection was generally mild, and the patients were treated as outpatient. There were no infection-related deaths and no opportunistic infection. Sixty percent of the patients were being treated for metastatic melanoma and 35.5% for non–small cell lung cancer, and 106 irAEs (mostly grade II) were reported. Forty-seven patients received steroids for cancer symptoms or irAEs, and five received immunosuppressants during the immunotherapy. We did not observe any association between corticosteroid or immunosuppressant use and the occurrence of an infection. The infection rate in patients treated with an anti–PD-1/PD-L1 ICI was 18%, without any severe or opportunistic infection. The occurrence of an infection was not associated with corticosteroid or immunosuppressant use. • Infections were searched for in 200 records from patients treated with ICIs. • The infection rate was 18%, without any severe or opportunistic infection. • Twenty-one patients (58.3%) had a lung infection. • The occurrence of an infection was not associated with immunosuppressant use. [ABSTRACT FROM AUTHOR]

Introduction The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient. Objective To report on efficacy and safety of TNF antagonists in severe and refractory sarcoidosis. Methods Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min–max) age = 45.5 (14–78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors. Results The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up ( p < 0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months). Conclusion TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events. [ABSTRACT FROM AUTHOR]

Background Long-term anticoagulation is recommended in antiphospholipid syndrome with thrombosis in order to prevent recurrences. While the current mainstay relies on vitamin K antagonists, their long-term maintenance may remain challenging. Objectives To report on the safety and the efficacy of oral direct inhibitors of thrombin and factor Xa (ODIs) in antiphospholipid syndrome (APS). Methods We performed a descriptive analysis of patients with APS enrolled in a French multicentre observational cohort between January 2012 and March 2014 and receiving ODIs. The main outcomes were the occurrence of a thrombotic recurrence or bleeding events. Results Twenty-six patients with APS (primary in 12) received ODIs. Twenty patients had been previously treated with VKA (n = 19), or fondaparinux (n = 1) for a median duration of 3 years. ODIs were introduced as second-line therapy because of INR lability/therapeutic simplification (n = 17), recurrent thrombosis (n = 1), VKA's associated bleeding event (n = 1), and atrial fibrillation (n = 1). Six patients received ODIs as first-line therapy. After a median [IQR] follow-up of 19 [8–29] months, one relapse of arterial thrombosis, two bleeding events (hypermenorrhea and rectal bleeding under rivaroxaban) and one recurrent migraine were reported, leading to discontinuation of therapy in these 4 patients. Conclusion ODIs might be an alternative therapeutic option in APS. Prospective studies are warranted to evaluate their safety in this condition. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3-ANCA) are a serological hallmark of small vessel vasculitis, particularly granulomatosis with polyangiitis (GPA). To increase their sensitivity, some ELISA employ the human native PR3 combined with a recombinant protein. Their specificity in daily practice is still to be defined. Our objective was to compare the performance for GPA diagnosis of three PR3-ANCA assays in daily practice. Patients and methods: Seventy-eight consecutive patients' sera with suggestive IIF were included. All sera were tested with a routine Enzyme Linked Immuno adsorbant Assay (ELISA) employing a mixture of human native and human recombinant (hn+hr) PR3 (EUROIMMUN™) compared to two assays using immobilized purified human PR3 (QUANTA Lite® ELISA and QUANTA Flash® Chemiluminescence assay (CIA), INOVA Diagnostics). Clinical data including BVAS score were collected retrospectively. Results: Nineteen out of the 78 patients had GPA. The hn+hr PR3 ELISA had a good sensitivity (100%) but a lower specificity for the diagnosis of GPA (61.0%) than the assays using the sole native protein (hn ELISA: 81.4%, hn CIA: 69.5%). False positive results mainly consisted of patients with inflammatory bowel disease, who had a specific PR3-ANCA positivity assembly when coupling the assays. The antibody titers by human native PR3 assays, but not hn+hr assay, positively correlated with BVAS score. Conclusion: These results highlight the need of a close collaboration between physicians and immunologists. Combining assays including last generation CIA employing human native antigens should improve the performance of GPA's diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To describe the small retinal and systemic vessel involvement in Takayasu''s arteritis. Methods: We described 3 patients with Takayasu''s arteritis and small retinal vessel occlusion seen in our department between 2004 and 2011. We performed an extensive literature review and provided a global analysis of small retinal vessel involvement in Takayasu arteritis (i.e., total number of patients analyzed=9). Results: Seven patients had small retinal artery occlusion, and two had venous involvement. Four cases were inaugural of the disease (44.4%). Takayasu''s arteritis was extended (Type V) in the majority of patients presenting with small retinal vessel occlusion (5/9, 55.6%), and 8/9 reported cases (88.9%) presented with involvement of the supra-aortic branches. Immunosuppressive regimen allowed an improvement in 5/9 patients and stabilization in 1/9, but the situation worsened in 3/9 patients. The visual outcome was severe, and 3/9 patients (33.3%) experienced irreversible blindness. Conclusion: Occlusion of small retinal vessels is a rare and severe microcirculatory complication in Takayasu''s arteritis, as well as necrotizing cutaneous vasculitis or myocarditis. Small retinal vessel involvement can be inaugural of the disease and seriously impact the visual prognosis in TA patients. [Copyright &y& Elsevier]

Plants are constantly exposed to a variety of biotic and abiotic stresses that reduce their fitness and performance. At the molecular level, the perception of extracellular stimuli and the subsequent activation of defense responses require a complex interplay of signaling cascades, in which protein phosphorylation plays a central role. Several studies have shown that some members of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) family are involved in stress and developmental pathways. We report here a systematic analysis of the role of the members of this gene family by mutant phenotyping in the monocotyledon model plant rice, Oryza sativa . We have then targeted 176 of the ∼320 LRR-RLK genes (55.7%) and genotyped 288 mutant lines. Position of the insertion was confirmed in 128 lines corresponding to 100 LRR-RLK genes (31.6% of the entire family). All mutant lines harboring homozygous insertions have been screened for phenotypes under normal conditions and under various abiotic stresses. Mutant plants have been observed at several stages of growth, from seedlings in Petri dishes to flowering and grain filling under greenhouse conditions. Our results show that 37 of the LRR-RLK rice genes are potential targets for improvement especially in the generation of abiotic stress tolerant cereals. [ABSTRACT FROM AUTHOR]

Introduction Le syndrome de Gleich ou angioedème avec hyperéosinophilie est une entité rare associant des crises récurrentes d'angioedème avec hyperéosinophilie concomitante et élévation fréquente d'immunoglobulines M sériques polyclonales. Patients et méthodes Nous avons conduit une étude rétrospective nationale multicentrique afin d'évaluer le spectre clinique et la prise en charge thérapeutique des angiœdèmes avec hyperéosinophilie. Résultats Trente patients ont été inclus avec un âge médian au diagnostic de 41 ans [5–84]. La durée médiane de chaque crise d'angiœdème était de 5,5 jours [1–90] avec atteinte principale du visage et des membres supérieurs. Le taux sériques d'immunoglobuline M était élevé pour 20 patients (67 %). Un phénotype lymphocytaire T aberrant était détecté chez 12 patients (40 %) avec mise en évidence d'un réarrangement clonal du TCR γ chez 5 de ces patients (17 %). Le suivi médian était de 53 mois [31-99]. Tous les patients ont reçu une corticothérapie initialement efficace, mais 15 patients ont rechuté après cette première ligne (50 %) justifiant une deuxième ou troisième ligne de traitement par interferon-α (n = 8,27 %), mepolizumab (n = 2,7 %), ciclosporine A (n = 5,17 %), methotrexate (n = 4,13 %) ou hydroxycarbamide (n = 2,7 %). La présence d'un phénotype lymphocytaire aberrant était le seul facteur associé aux rechutes (hazard ratio 4,15 [IC 95 % 1,18–14,66] ; p = 0,02). Lors du dernier suivi, 3 patients (10 %) étaient sevrés de tout traitement et 11 patients (37 %) étaient en rémission clinique et biologique sous moins de 10 mg d'équivalent prednisone par jour. Conclusion Le syndrome de Gleich ou angiœdème avec hyperéosinophilie est une entité hétérogène au sein des syndromes hyperéosinophiliques. Bien que les patients présentent une bonne réponse à la corticothérapie, les patients porteurs d'un phénotype lymphocytaire T aberrant ont un risque de rechute augmenté. [ABSTRACT FROM AUTHOR]