N-Glycan-Dependent Proinflammatory Effects of IgM in Anti-MAG Neuropathy.

Background And Objectives: Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a chronic demyelinating neuropathy with deposits of IgM and sural nerve fiber demyelination. While growing evidence supports the critical role of IgG glycosylation in autoimmune diseases, IgM glycosylation profiles markedly differ from those of IgG but are largely neglected. The aim of this study was to characterize IgM N-glycosylation in patients with anti-MAG neuropathy and its involvement in anti-MAG pathogenicity.

Serum interferon-beta level determined by an ultrasensitive electrochemiluminescence immunoassay is increased in clinically active and inactive systemic lupus erythematosus.

Type I interferons, which play an important role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE), are expressed at very low levels under physiological conditions. In this study, we focused on IFN-beta (IFN) β-for its potential use as a biomarker of SLE activity and compared three different technologies for its quantification in the serum of healthy donors and patients with SLE. A total of 93 serum samples from healthy donors and 463 serum samples from lupus patients were tested using either ELISA, digital ELISA based on Single Molecule Array (Simoa®) technology, or a novel ultrasensitive immunoassay (S-Plex®) based on electrochemiluminescence.

Single-Cell Profiling of Lichen Planus Reveals Type I IFN Response Triggering the Interface Dermatitis Reaction.

Cutaneous lichen planus (LP) is an inflammatory skin disease characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte (KC) cell death. The aim of this study was to investigate the immunopathogenesis of LP and assess the underlying mechanisms that drive the interface dermatitis reaction. We first performed single-cell RNA sequencing on lesional skins from patients with LP compared with healthy control skins and demonstrate that LP skin is imprinted by a type I IFN-rich environment.

Deep Immunophenotyping and Clustering Identifies Biomarkers Predictive of Lymphoma in Primary Sjögren Disease.

Objective: Patients with primary Sjögren disease (pSD) are prone to develop non-Hodgkin lymphoma (NHL), but relevant biomarkers are lacking. We aimed to determine new biomarkers predictive of NHL in patients with pSD.

Methods: Two hundred six patients with pSD fulfilling American College of Rheumatology/EULAR 2016 criteria were included and divided into three groups: pSD, lymphoproliferative pSD (Arl-pSD), and NHL-pSD.

Rapid Detection of Anti-IFN-α2 Autoantibodies Using a New Automated VIDAS Assay Prototype.

Autoantibodies neutralizing Type I interferons increase the risk of severe viral diseases and are linked to autoimmune conditions. The automated VIDAS assay is suitable for anti-IFN-α2 IgGs quantification, offering a swift, reliable, user-friendly, single test for clinical management.

Anti-RNApol3-Associated myocarditis: an emerging disease linking autoimmunity and infection.

Background: Fulminant myocarditis (FM) is a severe condition primarily triggered by viruses. Anti-RNA polymerase III autoantibodies (RNApol3) which are typically found in patients with severe systemic sclerosis, have been reported in patients with influenza-related FM. Our objective is to provide additional insight into RNApol3-associated FM.

Ultrasensitive interferons quantification reveals different cytokine profile secretion in inflammatory myopathies and can serve as biomarkers of activity in dermatomyositis.

Objective: The objective of this study was to evaluate the presence of different types of interferon in idiopathic inflammatory myopathies (IIM) and their subgroups using ultrasensitive cytokine detection techniques (SIMOA) and to assess their potential as activity biomarkers.

Methods: Disease activity was measured at the time of serum collection and assessed by manual muscle testing eight (MMT8 score 0-150), muscle enzymes to calculate the Physician Global Assessment (PGA) (0-10). Patients were classified as active if PGA>5.

Interferon-α biological activity is associated with disease activity and risk of flare in cutaneous lupus erythematosus: A monocentric study of 184 patients.

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 interferon-α (IFN-α) biological activity as biomarker of CLE activity and risk of flare.

Fever following extracorporeal membrane oxygenation decannulation: Infection, thrombosis or just physiology?

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.

Decreasing ganglioside synthesis delays motor and cognitive symptom onset in Spg11 knockout mice.

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.

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination.

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.

Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.

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.

Intestinal Candida albicans overgrowth in IgA deficiency.

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.

Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study.

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.

Binding and Kinetic Analysis of Human Protein Phosphatase PP2A Interactions with Caspase 9 Protein and the Interfering Peptide C9h.

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.