Publications by authors named "Guillaume le Guenno"

Background: pneumonia (PCP) has a significant mortality rate for non-HIV immunocompromised patients. Prevention is primarily based on combined trimethoprim and sulfamethoxazole (TMP-SMX) but guidelines on pneumocystosis prophylaxis are scattered and not consensual.

Objectives: This study aims to describe PCP in non-HIV patients and to review case by case the prior indication of prophylaxis according to specific guidelines.

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Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.

Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy.

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Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG.

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Article Synopsis
  • Recent findings show that mutations in the UBA1 gene are linked to VEXAS syndrome, an adult-onset auto-inflammatory condition, but the exact effects of these mutations are not well understood.
  • Research on a group of VEXAS patients indicates that their monocytes are not functioning properly and exhibit signs of exhaustion and altered chemokine receptor expression.
  • The study also highlights elevated levels of inflammatory cytokines in the blood of VEXAS patients, pointing to possible therapeutic targets related to inflammasome activation and inflammatory cell death.
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  • VEXAS syndrome is a poorly understood, acquired autoinflammatory disease linked to serious infections, highlighting significant risks for susceptible patients.
  • A study of 74 patients revealed that the most frequent infection sites were the lungs, skin, and urinary tract, with a notable microbiological confirmation rate.
  • Key risk factors for serious infections included age over 75, specific genetic mutations, and treatment with JAK inhibitors, with 36% of patients dying during the study, often due to these severe infections.
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Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs), conferring a predisposition to life-threatening COVID-19 pneumonia. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52/IκBδ).

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  • Treatment strategies for autoimmune acquired pure red cell aplasia (aPRCA) are tough due to a lack of controlled trials, and guidelines are based mainly on expert opinions.
  • A systematic review and meta-analysis of 24 observational studies with 753 patients showed varying effectiveness among treatments, with corticosteroids yielding a 47% overall response rate (ORR) and cyclosporine A leading to a higher ORR of 74%.
  • Cyclophosphamide showed a 49% ORR, and sirolimus, typically used after other treatments fail, exhibited an impressive ORR of 87%, highlighting that more research is needed to determine the best approaches for aPRCA management.
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Background: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.

Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.

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  • - The study examined the characteristics of granulomatosis with polyangiitis (GPA) in patients who experienced induction failure, focusing on different treatments and how effective salvage therapies were from 2006 to 2021.
  • - A total of 51 patients with GPA and induction failure were analyzed, revealing that those treated with intravenous cyclophosphamide often had more severe symptoms like relapsing disease and orbital masses compared to controls, while those on rituximab showed significant renal complications.
  • - After trying salvage therapies, 69% of patients achieved remission, with a notable success in switching therapies; 50% of those inadequately responding to cyclophosphamide improved with rituximab, while patients progressing
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  • VEXAS syndrome is an autoinflammatory condition linked to mutations, characterized by vacuoles in myeloid progenitors and somatic changes.
  • A study by Heiblig et al analyzed 30 patients with VEXAS syndrome who were treated with various Janus kinase (JAK) inhibitors.
  • The findings showed positive results for the JAK1/2 inhibitor ruxolitinib, leading to clinical remissions and less reliance on steroids for most patients.
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We report an atypical Borrelia garinii infection in a patient who was immunocompromised. It was first suspected as a transformation of follicular lymphoma into high-grade lymphoma. Spirochetes were directly observed on a peripheral blood smear and the diagnosis was confirmed using molecular methods.

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Background And Objectives: Spinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurologic sequelae for the patient. We investigated prognostic factors and efficacy of immunosuppressive treatments in a longitudinal cohort.

Methods: We retrospectively studied patients with spinal cord sarcoidosis followed between 1995 and 2021 in 7 centers in France.

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The transient occlusion of the terminal thoracic duct is a rare disease responsible for renitent supraclavicular cysts. The aim of this study was to describe the clinical characteristics, evolution, and treatment.A retrospective multicenter study and literature review was carried out.

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Objectives: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE.

Methods: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded.

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Article Synopsis
  • * A study using data from a French nationwide registry included 116 VEXAS patients, focusing on 11 individuals with concurrent MDS treated with azacitidine.
  • * Out of the 11 treated patients, five (46%) exhibited clinical responses to azacitidine, highlighting its potential as a treatment option for select VEXAS patients experiencing MDS.
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Background: Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late-onset presentation may delay its diagnosis until adulthood.

Objective: To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood.

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Background: Cardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to systematically review 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 standard immunosuppressive therapies for CS that provided at least a fair Scottish Intercollegiate Guidelines Network (SIGN) overall assessment of quality and we analysed the relapse rate, major cardiac adverse events (MACEs) and adverse events.

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Purpose: 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-α) 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.

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Article Synopsis
  • * All patients received initial corticosteroid and immunosuppressive therapies before transitioning to TNFα antagonists after relapses, with one experiencing a minor relapse that was managed effectively.
  • * No serious side effects were reported, suggesting TNFα antagonists could be a safe and effective option for treating difficult cases of CS earlier in the treatment process.
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Objective: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA.

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