Clinical correlates of lifetime and current comorbidity patterns in autoimmune and inflammatory diseases.

Background: Autoimmune and inflammatory diseases (AIDs) are a heterogeneous group of disorders with diverse etiopathogenic mechanisms. This study explores the potential utility of family history, together with present and past comorbidities, in identifying distinct etiopathogenic subgroups. This approach may facilitate more accurate diagnosis, prognosis and personalized therapy.

Amorphous calcium carbonate enhances osteogenic differentiation and myotube formation of human bone marrow derived mesenchymal stem cells and primary skeletal muscle cells under microgravity conditions.

Astronauts are exposed to severely stressful physiological conditions due to microgravity and increased space radiation. Space environment affects every organ and cell in the body and the significant adverse effects of long-term weightlessness include muscle atrophy and deterioration of the skeleton (spaceflight osteopenia). Amorphous Calcium Carbonate (ACC) emerges as a promising candidate for prevention of these effects, owing to its unique physicochemical properties and its potential to address the intricately linked nature of bone-muscle crosstalk.

High risk of lung cancer in surfactant-related gene variant carriers.

Background: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers.

Methods: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

Background And Objective: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults.

Methods: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed.

Hypomorphic pathogenic variant in SFTPB leads to adult pulmonary fibrosis.

Biallelic pathogenic variants in the surfactant protein (SP)-B gene (SFTPB) have been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We herein report the cases of two related adults with pulmonary fibrosis due to a new homozygous SFTPB pathogenic variant, c.582G>A p.

A critical region of A20 unveiled by missense variations that lead to autoinflammation.

A20 haploinsufficiency (HA20) is an autoinflammatory disease caused by heterozygous loss-of-function variations in , the gene encoding the A20 protein. Diagnosis of HA20 is challenging due to its heterogeneous clinical presentation and the lack of pathognomonic symptoms. While the pathogenic effect of truncating variations is clearly established, that of missense variations is difficult to determine.

Pharmacological options in the treatment of osteogenesis imperfecta: A comprehensive review of clinical and potential alternatives.

Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder characterized by bone fragility and different extra-skeletal manifestations. The severity of these manifestations makes it possible to classify OI into different subtypes based on the main clinical features. This review aims to outline and describe the current pharmacological alternatives for treating OI, grounded on clinical and preclinical reports, such as antiresorptive agents, anabolic agents, growth hormone, and anti-TGFβ antibody, among other less used agents.

The Effect of Outer Space and Other Environmental Cues on Bacterial Conjugation.

Bacterial conjugation is one of the most abundant horizontal gene transfer (HGT) mechanisms, playing a fundamental role in prokaryote evolution. A better understanding of bacterial conjugation and its cross talk with the environment is needed for a more complete understanding of HGT mechanisms and to fight the dissemination of malicious genes between bacteria. Here, we studied the effect of outer space, microgravity, and additional key environmental cues on transfer ( gene expression and conjugation efficiency, using the under studied broad-host range plasmid pN3, as a model.

De Novo Gain-Of-Function Variations in LYN Associated With an Early-Onset Systemic Autoinflammatory Disorder.

Objective: To identify the molecular basis of a severe systemic autoinflammatory disorder (SAID) and define its main phenotypic features, and to functionally assess the sequence variations identified in LYN, a gene encoding a nonreceptor tyrosine kinase.

Methods: We used targeted next-generation sequencing and in vitro functional studies of Lyn phosphorylation state and Lyn-dependent NF-κB activity after expression of recombinant Lyn isoforms carrying different sequence variations.

Results: We identified a de novo LYN variation (p.

Neutrophilic dermatoses.

Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome.

Mosaic variants in TNFRSF1A: an emerging cause of tumour necrosis factor receptor-associated periodic syndrome.

Objective: To identify the molecular basis of a systemic autoinflammatory disorder (SAID) evocative of TNF receptor-associated periodic syndrome (TRAPS).

Methods: (i) Deep next generation sequencing (NGS) through a SAID gene panel; (ii) variant allele distribution in peripheral blood subpopulations; (iii) in silico analyses of mosaic variants using TNF receptor superfamily 1A (TNFRSF1A) crystal structure; (iv) review of the very rare TNFRSF1A mosaic variants reported previously.

Results: In a 36-year-old man suffering from recurrent fever for 12 years, high-depth NGS revealed a TNFRSF1A mosaic variant, c.

High Nasal Nitric Oxide, Cilia Analyses, and Genotypes in a Retrospective Cohort of Children with Primary Ciliary Dyskinesia.

Although children with primary ciliary dyskinesia (PCD) typically have low nasal nitric oxide (nNO), some children with indisputable PCD may have unexplained high nNO concentrations. To look for relationships between nNO measures and genetic findings (and cilia motility or ultrastructure when available) in children with PCD with known genotypes. We retrospectively studied 73 children with PCD (median age, 9.

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability.

Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy. Dysfunction of motile respiratory and nodal cilia results in sinopulmonary symptoms associated with laterality defects (LD) found in half of the patients. The molecular basis of the disease is insufficiently investigated in patients originating from the Arabian Peninsula.

Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort.

Introduction: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.

Methods: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases).

RaDiCo, the French national research program on rare disease cohorts.

Background: Rare diseases (RDs) affect nearly 3 million people in France and at least 26-30 million people in Europe. These diseases, which represent a major medical concern, are mainly of genetic origin, often chronic, progressive, degenerative, life threatening and disabling, accounting for more than one third of all deaths occurring during infancy. In this context, there are needs for coordinated information on RDs at national/international levels, based on high quality, interoperable and sharable data.

Impact of Gender on the Characteristics of Patients with Idiopathic Pulmonary Fibrosis Included in the RaDiCo-ILD Cohort.

Background: There is growing evidence of gender-specific phenotypic differences among patients with idiopathic pulmonary fibrosis (IPF), which may affect patient outcomes.

Objectives: We present the characteristics of patients with IPF at inclusion in the French Rare Disease Cohort - Interstitial Lung Disease (RaDiCo-ILD) with the aim of characterizing gender-specific phenotypic differences.

Methods: Patients with IPF who were enrolled in the national, multicentre RaDiCo-ILD cohort were included.

Chronic hepatic involvement in the clinical spectrum of A20 haploinsufficiency.

Background & Aims: Secondary to tumour necrosis factor-alpha induced protein 3 (TNFAIP3) mutations, A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease with clinical features similar to those of Behçet's and Crohn's diseases but with a constantly expanding clinical spectrum. Here, we describe HA20 liver involvement in three new patients from the same family.

Methods: We retrospectively assessed clinical, biological and/or histological findings for eight patients over three generations of the same family with heterozygous mutations in the TNFAIP3 gene (c.

Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders.

Among the genetic factors playing a key role in the etiology of intellectual disabilities (IDs) and autism spectrum disorders (ASDs), several encode RNA-binding proteins (RBPs). In this study, we deciphered the molecular and cellular bases of ID-ASD in a patient followed from birth to the age of 21, in whom we identified a de novo CSDE1 (Cold Shock Domain-containing E1) nonsense variation. CSDE1 encodes an RBP that regulates multiple cellular pathways by monitoring the translation and abundance of target transcripts.

Tumour necrosis factor receptor-1 associated periodic syndrome (TRAPS)-related AA amyloidosis: a national case series and systematic review.

Objectives: TNF receptor-1-associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder associated with mutations in the TNF receptor super family 1 A (TNFRSF1A) gene. AA amyloidosis (AA) is the most severe complication of TRAPS. To study the occurrence and prognosis of AA in TRAPS, we conducted a retrospective study of all French cases and a systematic literature review.