Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency : Report on 30 Patients

Correction; Early Access: ' DOI: 10.1007/s10875-022-01280-y Early Access: APR 2022Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-alpha) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.Peer reviewe

Correction to: Hematopoietic cell transplantation cures adenosine deaminase 2 deficiency: report on 30 patients

Correction to: Journal of Clinical Immunology (2021) 41:1633–164

Evénements thrombotiques au cours du purpura thrombopénique immunologique (une étude cas témoins)

Le purpura thrombopénique immunologique (PTI) de l'adulte est une pathologie fréquente et dans la majorité des cas bénigne. Bien que les complications hémorragiques soient bien connues, le PTI semble s'associer à une augmentation du risque thrombotique. Le but de notre travail est de décrire les événements thrombotiques survenus au cours du PTI, puis d'identifier des facteurs de risque grâce à une étude cas-témoins. Parmi les PTI suivis dans le service sur une période de 11,2 ans, ceux ayant présenté un événement thrombotique ont été inclus puis appariés par le sexe et l'âge à 2 témoins. Les données colligées comprenaient les données des patients, les caractéristiques du PTI et de l'événement thrombotique. Une analyse uni puis multivariée a été effectuée. Sur 386 patients, 25 événements thrombotiques ont été retrouvés chez 18 patients soit un taux d'événement de 6,5%. Ces thromboses étaient en majorité veineuses (n=21 : 11 phlébites profondes des membres inférieurs, 6 embolies pulmonaires, 3 thrombophlébites cérébrales, 1 thrombose porte). On notait 1 événement thrombotique artériel (accident vasculaire cérébral) et 2 événements combinés. Les événements thrombotiques survenaient à des taux bas de plaquettes (médiane 68 G/L). Les seuls facteurs associés à la survenue de thrombose en analyse univariée étaient un antécédent de thrombose veineuse (p=0.03), la présence d'un marqueur biologique antiphospholipide (APL) (p=0,026), et plus particulièrement l'anticoagulant circulant (p=0,003). En analyse multivariée, seule la sérologie antiphospholipide positive constituait un facteur de risque de thrombose. Les patients suivis pour un PTI présentent un risque notable d'événement thrombotique même en étant thrombopénique. Les thromboses, majoritairement veineuses, surviennent fréquemment chez les patients aux antécédents de maladie thromboembolique veineuse et chez ceux porteurs d'anticorps antiphospholipides. Leur recherche se doit d'être systématique lors du diagnostic de PTI. Le seuil thérapeutique devrait être adapté systématiquement à chaque patient en mettant en balance risque hémorragique et risque thrombotique grâce à la prise en compte des facteurs de risque.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

ANCA-associated vasculitis and malignancy: Current evidence for cause and consequence relationships

In this review, we summarise the current understanding of the potential link between cancer and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (Wegener's; GPA) and microscopic polyangiitis (MPA). As is true for many autoimmune or inflammatory rheumatic diseases, AAV diagnosis and therapy are associated with an increased risk of de novo cancer development, likely as a result of impaired immunosurveillance, direct oncogenicity of immunosuppressive agents and perhaps malignant degeneration of tissues undergoing chronic immune stimulation. Data from several studies suggest a standardised incidence ratio of cancer in AAV of 1.6-2.0 compared to the general population and a possibly higher risk in GPA than in MPA. The most prominent cancers observed in AAV include urinary tract cancer, leukaemia and non-melanoma skin cancer. The effect of individual therapeutic agents is difficult to dissect, but cyclophosphamide has emerged as a major contributor to cancer development because of its direct carcinogenic properties. Awareness of cancer risk in AAV calls for increased implementation of measures to prevent or screen for cancer and development of less carcinogenic therapies. Cancer has also been suggested as a potential trigger or cause of AAV. Although some studies found that prior or concomitant history of cancer increases the risk of AAV, available data are inconsistent and suggest that the fraction of AAV that might be attributable to cancer is at best small. (C) 2012 Elsevier Ltd. All rights reserved

Study of iron metabolism disturbances in an animal model of insulin resistance

International audienceThe relationship between iron and insulin-resistance (IR) is documented by the positive correlation between iron stores and IR. Moreover, some patients exhibited a hepatic iron overload associated with IR (HIO-IR) but the mechanism involved in this overload is not known. Thus, we studied the iron metabolism disturbances in an animal model of IR and the influence of provoked hyperglycemia/hyperinsulinemia on plasma iron parameters. Wistar rats were fed a control or a high-fat/high-energy (HF/HE) diet. Plasma glucose, insulin, iron, transferrin and transferrin saturation (TS) were measured during intra-peritoneal glucose test tolerance (IPGTT) compared to saline. Hemogram, tissue iron concentrations and hepatic hepcidin mRNA expression were determined at the end of experiment. HF/HE rats exhibited higher body and liver weights, increased IR-index and hemoglobin concentration. Iron content was lower in the spleen of HF/HE rats and tended to decrease in the liver as compared to controls. Transferrin values were higher and these of TS lower in HF/HE group. The hepcidin mRNA was 3.5-fold lower in HF/HE rats than in controls. IPGTT had no effect on iron status parameters in both groups. As reflected by higher hemoglobin concentration, IR could increase erythropoïesis which enhances iron requirement. Iron stores and TS value decreased leading to a down-regulation of hepcidin expression which increased iron absorption. Hepcidin expression should be investigated in metabolic syndrome and hepatic iron overload associated with IR

Case report: TNFα antagonists are an effective therapy in cardiac sarcoidosis

International audienceIntroduction: Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists. Methods: We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists. Results: Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34–53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25–115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT. Conclusion: TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme

Cardiac sarcoidosis: systematic review of literature on corticosteroid and immunosuppressive therapies

International audienceBackground Cardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to review systematically the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS. Methods Using Pubmed, Embase and Cochrane Library databases, we found original articles on corticosteroid and/or standard immunosuppressive therapies for CS which provided at least fair SIGN overall assessment of quality and analyse the relapse rate, major cardiac adverse events (MACEs) and adverse events. We base our methods on Prisma statement and checklist. Results We retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8/14 (range 5–9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block, and ventricular arrhythmias. For corticosteroids alone, nine (45%) studies (n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy in which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted in no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids.Conclusions Corticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking

Computed and Subjective Blue Scleral Color Analysis as a Diagnostic Tool for Iron Deficiency: A Pilot Study

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Atypical Borrelia garinii infection in an immunocompromised patient mimicking high-grade lymphoma

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Fluorescent in situ hybridization can be used as a complementary assay for the diagnosis of Tropheryma whipplei infection

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