Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo

Mutations in STAT3 and IL12RB1 impair the development of human IL-17 producing T cells

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Agglutinines froides, circonstances de découverte chez l'adulte et signification en pratique clinique (analyse rétrospective à propos de 58 patients)

Les agglutinines froides (AF) sont rares, leur pouvoir pathogène est extrêmement variable, fonction de multiples facteurs, et leur prise en charge thérapeutique souvent difficile. Ce travail, divisé en deux grands chapitres, avait pour objectif d'analyser la signification de la présence d'une AF en pratique clinique et d'étudier l'impact d'un traitement par anticorps (AC) monoclonal anti-CD20 (Rituximab) en cas d'AF symptomatique. Deux études rétrospectives ont pour cela étaient menées. Dans la première étude (1) (1997-2002), 58 patients ayant une recherche spécifique d'AF positive étaient analysés: paramètres cliniques et d'hémolyse, caractéristiques immuno-hématologiques, pathologies associées. Les manifestations cliniques et biologiques étaient hautement variables entre menace vitale par hémolyse intra-vasculaire et l'absence de symptomatologie. L'intensité de ces manifestations était, le plus souvent, corrélée aux caractéristiques immuno-hématologiques des AF in vitro, témoignant de leur agressivité, (intensité et spécificité du TCD, titre, amplitude thermique). Les causes secondaires étaient prévalentes (77,6%): maladies auto-immunes (n=19), hémopathies lymphoïdes (n=11), infections (n=10) avec une fréquence remarquable de l'hépatite C chronique (4/10). Cette série soulignait l'intérêt d'une concertation clinicien biologiste en cas de discordance entre manifestations cliniques et caractéristiques biologiques in vitro et rappellait la nécessité de prolonger la recherche d'hémopathie lymphoïde devant une AF idiopathique. Dans la deuxième étude (2) (2002-2005), 9 patients traités par Rituximab du fait d'une anémie hémolytique (8/9) et/ou d'un acrosyndrome (4/9) étaient étudiés. Une excellente réponse clinico-biologique était obtenue dans la majorité des cas (7/9). Par contre, il n'y avait pas d'éradication du syndrome lymphoprolifératif sous-jacent ni de l'auto-AC et les caractéristiques immuno-hématologiques des AF in vitro restaient généralement inchangées suggérant que le Rituximab a d'autres potentialités que la seule élimination des cellules B, tumorales ou non, productrices d'auto-AC: interférence avec la fixation et l'activation du complément ou avec la présentation antigénique.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Infliximab in the treatment of refractory vasculitis secondary to hepatitis C-associated mixed cryoglobulinaemia

International audienc

Contribution of molecular tools for the diagnosis of endogenous pneumococcal endophthalmitis in a patient with the acquired immunodeficiency syndrome

Confirmation of infectious endophthalmitis is a major challenge. Traditional microbial tools are frequently unsuccessful mostly due to very small fluid samples and prior use of antibiotics. Here we report the first case of Streptococcus pneumoniae endophthalmitis diagnosed by polymerase chain reaction. Molecular biology should be considered as a new tool for the diagnosis of such sequestered sites as the eye

Complete remission of a relapsing adult T cell leukaemia following treatment of a secondary acute promyelocytic leukaemia: towards a reappraisal of arsenic trioxide and all-transretinoic acid?

Despite improvements in therapeutic options, human T cell lymphotropic virus type 1 (HTLV-1)-related adult T cell leukaemia/lymphoma (ATLL) has a dismal prognosis. The present report concerns the case of a multirelapsing ATLL that reached a complete remission following the treatment of a secondary acute promyelocytic leukaemia with cytarabine, anthracyclin, all-transretinoic acid and arsenic trioxide. This unexpected result with a multitreated/chemorefractory disease led us to reconsider the potential therapeutic benefits of arsenic trioxide, which has demonstrated efficacy against ATLL cells

Imported African Histoplasmosis in an Immunocompetent Patient 40 Years after Staying in a Disease-Endemic Area

International audienceHistoplasmosis caused by Histoplasma capsulatum var. duboisii is a rare disease outside central and western Africa. In Europe, all cases are imported. We report a case of an African histoplasmosis with isolated pulmonary involvement in a non-immunocompromised patient that occurred 40 years after his stay in a disease-endemic area. The patient was given itraconazole. (18)F-fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography was used to assess evolution during treatment. The outcome for the patient was favorable

Granulocyte Colony Stimulating Factor-induced Exacerbation of Fungus-related Immune Restoration Inflammatory Syndrome: A Case of Chronic Disseminated Candidiasis Exacerbation

International audienceChronic disseminated candidiasis is a complication of the intensive therapies of hematological malignancies revealed during hematopoietic recovery, a context reminiscent of the immune restoration inflammatory syndrome in human immunodeficiency virus patients receiving antiretroviral therapy. We report a case of severe exacerbation of chronic disseminated candidiasis after pegylated granulocyte-colony stimulating factor administration. We emphasize the major inflammatory substrate of the disease and suggest that immune-modulating strategies such as hematopoietic growth factors, should be used cautiously in such patients

Antifungal Therapy of Aspergillus Invasive Otitis Externa: Efficacy of Voriconazole and Review▿

Invasive otitis externa (IOE) due to Aspergillus is a rare, potentially life-threatening, invasive fungal infection affecting immunocompromised patients. The invasive process may lead to skull base osteomyelitis with progressive cranial nerve palsies and can result in irreversible hearing and neurological impairment. We report two cases of Aspergillus IOE treated with voriconazole alone and a literature review of antifungal therapy of Aspergillus IOE. Twenty-five patients, including the two described in the present report, were analyzed. Eighteen patients were treated with amphotericin B, and nine of them received itraconazole as an additional agent. Three patients received initial therapy with itraconazole, and one patient was treated with both voriconazole and caspofungin therapy. The two patients in the present report received voriconazole therapy alone with good clinical and biological tolerance despite prolonged treatment. The last patient did not receive antifungal therapy, as the diagnosis was made postmortem. Eighteen patients underwent an initial extensive surgical debridement. The majority of the patients had a favorable outcome, 17 patients experienced a complete recovery, and 6 showed a partial improvement. Both of the patients reported on here had favorable outcomes, and no aggressive surgical debridement was required. Although voriconazole has been shown to be effective for the treatment of invasive aspergillosis, its precise role in the management of Aspergillus IOE had not been documented. These observations demonstrate that voriconazole could be an effective and well-tolerated therapeutic option for the management of Aspergillus IOE