Publications by authors named "Dorgham K"

Background: Cutaneous Lupus Erythematosus (CLE) is associated with unpredictable flares and may induce permanent damage. There is currently no biomarker routinely available in CLE.

Objective: To evaluate the performance of IFN-α biological activity as biomarker of CLE activity and risk of flare.

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Purpose: Fever is frequent after extracorporeal membrane oxygenation (ECMO) decannulation. We aimed to evaluate the incidence of post-decannulation fever and describe its causes.

Methods: Adult ECMO patients who were successfully weaned from ECMO were retrospectively included.

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  • * A study examined 131 female patients with X-linked dominant incontinentia pigmenti (IP), finding that 36% produced autoantibodies against IFN-α and/or IFN-ω, significantly higher than age-matched controls.
  • * The presence of these autoantibodies is linked to an abnormally small thymus and predisposes patients to life-threatening viral infections, while those without these autoantibodies do not face the same risk.
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  • - The study investigated changes in biological, clinical, and imaging markers in carriers of spinocerebellar ataxia (SCA) types 2 and 7 over one year, focusing on MRI and neurofilament light chain (NfL) levels.
  • - It included assessments of neurological function, quality of life, and brain imaging among 15 SCA2 carriers, 15 SCA7 carriers, and 10 control subjects, while noting differences in SARA scores and brain volume from baseline measurements.
  • - Results indicated significant brain volume loss and worsening motor function in SCA2 carriers, an increase in SARA scores and thinning of retinal layers in SCA7, highlighting the progressive nature of these at
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Biallelic variants in the SPG11 gene account for the most common form of autosomal recessive hereditary spastic paraplegia characterized by motor and cognitive impairment, with currently no therapeutic option. We previously observed in a Spg11 knockout mouse that neurodegeneration is associated with accumulation of gangliosides in lysosomes. To test whether a substrate reduction therapy could be a therapeutic option, we downregulated the key enzyme involved in ganglioside biosynthesis using an AAV-PHP.

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Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response.

Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection.

Design, Setting, And Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France.

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  • The study investigates the levels of HIV RNA and cytokines in adolescents who have been on antiretroviral treatment (ART) since early in life, focusing on potential indicators for clinical trials aimed at finding a cure for HIV.
  • It enrolled 40 perinatally infected adolescents on ART for over 5 years, measuring various HIV markers and correlating them with clinical characteristics.
  • Results show that lower levels of cell-associated RNA (CA-RNA) are linked to lower levels of cell-associated DNA (CA-DNA), and that undetectable CA-RNA is associated with factors like earlier initiation of ART and higher Western Blot scores.
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GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden.

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  • COVID-19 severity is linked to dysregulated immune responses, particularly due to natural killer (NK) cell dysfunction in critically ill patients.
  • A study with 50 non-vaccinated hospitalized patients highlighted that NK cells in COVID-19 patients were more activated but had impaired function, correlating with disease severity and patient outcomes.
  • Findings indicate that an uncoordinated inflammatory response, driven by a specific subset of activated NK cells, may contribute to fatalities in severe COVID-19 cases.
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Background: Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown.

Objectives: Our goal was to study the impact of IgA on gut mycobiota ecology.

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  • The study aimed to explore inflammation through cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients experiencing new-onset refractory status epilepticus (NORSE) to better understand its underlying mechanisms and impacts.
  • Researchers analyzed data from 61 NORSE patients, including those with the subtype febrile infection-related epilepsy syndrome (FIRES), and compared them to other refractory status epilepticus patients and controls, measuring 12 specific cytokines/chemokines.
  • Results showed significant increases in several pro-inflammatory cytokines in SE patients, particularly in those with cryptogenic NORSE, and higher levels were linked to poorer health outcomes, indicating a crucial role of inflammation in NORSE.
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Background: Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs.

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The serine/threonine phosphatase PP2A and the cysteine protease Caspase 9 are two proteins involved in physiological and pathological processes, including cancer and apoptosis. We previously demonstrated the interaction between Caspase 9 and PP2A and identified the C9h peptide, corresponding to the binding site of Caspase 9 to PP2A. This interfering peptide can modulate Caspase 9/PP2A interaction leading to a strong therapeutic effect in vitro and in vivo in mouse models of tumor progression.

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Objectives: Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown.

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  • - The study examines adults suffering from fulminant myocarditis related to COVID-19, identifying two distinct groups: those meeting multisystem inflammatory syndrome criteria (MIS-A) and those who do not.
  • - Out of 38 patients analyzed, 66% met the MIS-A criteria, with significant differences in clinical outcomes; those with MIS-A exhibited higher in-hospital mortality (31% vs. 4%) and more severe organ failure.
  • - Biological markers also varied between the groups, suggesting differing underlying inflammatory processes, which could impact treatment approaches in future cases of COVID-19-related myocarditis.
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  • Breakthrough cases of severe COVID-19 in vaccinated individuals may be linked to weak or inadequate antibody responses, particularly among those already at risk.
  • A study of 48 vaccinated individuals with hypoxemic COVID-19 pneumonia found that about 24% had auto-antibodies (auto-Abs) that neutralized type I interferons, which are essential for the immune response.
  • The presence of these auto-Abs suggests that even with normal antibody responses to the vaccine, some individuals can still suffer severe effects from COVID-19, indicating a need for more targeted strategies for vulnerable populations.
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The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF).

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Background: Identifying subphenotypes within heterogeneous diseases may have an impact in terms of therapeutic options. In this study, we aim to assess different subphenotypes in children living with human immunodeficiency virus (HIV-1), according to the clinical, virological, and immunological characteristics.

Methods: We collected clinical and sociodemographic data, baseline viral load (VL), CD4 and CD8 count and percentage, age at initiation of ART, HIV DNA reservoir size in peripheral blood mononuclear cells (PBMCs), cell-associated RNA (CA-RNA), ultrasensitive VL, CD4 subsets (T effector CD25+, activated memory cells, Treg cells), humoral-specific HIV response (T-bet B cells), innate response (CD56dim natural killer (NK) cells, NKp46+, perforin), exhaustion markers (PD-1, PD-L1, DNAM), CD8 senescence, and biomarkers for T-lymphocyte thymic output (TREC) and endothelial activation (VCAM).

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers.

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The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults remain poorly understood. Bronchoalveolar lavage (BAL) and peripheral blood sampling were performed in 74 steroid and non-steroid-treated intensive care unit (ICU) patients (23-75 years; 44 survivors). Peripheral effector SARS-CoV-2-specific T cells were detected in 34/58 cases, mainly directed against the S1 portion of the spike protein.

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  • Autosomal recessive complete IRF8 deficiency is a rare immune disorder leading to severe infections and absence of specific blood cells, with only three other cases previously documented.
  • An Argentinian child with severe pulmonary issues and multiple infections was studied, revealing two genetic mutations in the IRF8 gene responsible for the condition.
  • The findings suggest that this genetic mutation hampers immune cell development, linking AR complete IRF8 deficiency to pulmonary alveolar proteinosis, and highlighting the need for awareness of this disorder in similar pediatric cases.
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The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM.

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