Nov 14th, 2022 - Background/Purpose: Homozygote (HM)/compound heterozygote (CH) and digenic (DG) mutations in proteasome subunits cause the autoinflammatory syndrome CANDLE, or proteasome-associated autoinflammatory syndrome (PRAAS). Inflammation is mediated by type I interferon (IFN I) due to proteotoxic distress, partially through protein kinase R (PKR) activation1. Patients (pts) with heterozygous (HZ) loss ...

Nov 14th, 2022 - Background/Purpose: NLRP3-associated autoinflammatoy disease (NLRP3-AID) and NLRP12-AID are rare autosomal dominant diseases. FACS1(familial cold autoinflammatory syndrome type 1), a subset of NLRP3-AID, is thought to be phenotypically similar to FCAS2(NLRP2-AID). NLRP3 and NLRP12 are members of the NOD-like receptors(NLRs) and their gene mutations contribute to these diseases. This study aimed...

Nov 14th, 2022 - Background/Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease, characterized by early‑onset vasculopathy, fever, strokes, livedoid rash, hepatosplenomegaly, and hematologic dysfunction, associated with mutations in the ADA2 gene, which was first described in 2014, DADA2 is usually reported in pediatric patients, with 77% before the age of 10 ...

Nov 14th, 2022 - Background/Purpose: Relapsing polychondritis (RP) is a rare rheumatic disease of unknown etiology characterized by inflammations of cartilaginous structures and other tissues, particularly the ears, nose, joints, airway, and blood vessels. Familial clustering in RP has been observed, which suggests a possible causal role of germline genetic variation. The objective of this study was to examine ...

Nov 14th, 2022 - Background/Purpose: SLE disproportionately affects individuals of African (AA) compared to European ancestry (EA). In addition to a higher incidence, the disease is more severe in patients of AA; they have a higher burden of renal comorbidities such as end stage renal disease (ESRD) and others (1). A high risk (HR) genotype in apolipoprotein L1 (APOL1), present in 13% of AA and absent in EA ind...

Nov 14th, 2022 - Background/Purpose: Dysregulated autophagy is implicated in systemic lupus erythematous (SLE) and Sjögren’s disease (SjD), including dysregulated expression of Autophagy-related gene 5 (ATG5) and Autophagy Related 16 Like 2 (ATG16L2) [1-3]. ATG16L2–P2RY2 and PRDM1–ATG5 loci are genome-wide significant (GWS) association in SLE [3,4]. This study aims to identify autophagy-related SLE and SjD ris...

Nov 14th, 2022 - Background/Purpose: Sjögren’s Disease (SjD) and Systemic Lupus Erythematosus (SLE) share several characteristics and have similar genome-wide significant associations in the DDX6-CXCR5 locus. Fine mapping of the DDX6-CXCR5 risk locus will refine the association signals and identify the most likely functional SNPs common across the two diseases. Methods: ImmunoChip data from European ancestry (3...

Nov 14th, 2022 - Background/Purpose: Calcinosis, deposition of insoluble calcium salts in skin and subcutaneous tissues, affects up to 40% of systemic sclerosis (SSc) patients, and up to 20% of adult dermatomyositis (DM) patients. It contributes to a significant disease burden as patients suffer from pain, ulceration, and secondary infections. The genetics of calcinosis in SSc and DM has not been investigated a...

Nov 14th, 2022 - Background/Purpose: Sle1 and FASlpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus (SLE) by altering the FAS/FASL pathway and adaptive immunity. Although C57BL/6 (B6) mice bearing either of these genes display mild phenotypes, the epistatic interaction of Sle1 and FASlpr results in severe lupus, confirming that these two genes impact non-redundant,...

Nov 14th, 2022 - Background/Purpose: RA-associated interstitial lung disease (RA-ILD) is an extra-articular manifestation of RA causing substantial morbidity and mortality. Genetic risk variants, such as the MUC5B rs35705950 promoter variant, have been linked to both idiopathic pulmonary fibrosis and RA-ILD. The purpose of this study was to validate these findings in a large RA cohort and to evaluate for the pr...

Nov 13th, 2022 - Background/Purpose: A set of genes has been associated with aortopathies, which are defined as non-inflammatory diseases where the integrity of large arteries is compromised leading to dilatation, aneurysm, and dissections. Overlap can exist between the clinical features of aortopathies and Takayasu’s arteritis (TAK), a form of large vessel vasculitis characterized by vascular inflammation of t...

Nov 13th, 2022 - Background/Purpose: Evidence suggest that autoimmune diseases tend to coexist at a higher rate than expected, reflecting a common pathogenetic pathway. However, data sets have shown an inverse association between certain autoimmune diseases, such as in Rheumatoid Arthritis and Multiple Sclerosis. In this study we investigate the co-occurrence of systemic sclerosis (SSc), Systemic lupus Erythema...

Nov 13th, 2022 - Background/Purpose: CD40 is a membrane glycoprotein expressed on B cells surface that activates antigen presenting cells [1]. BLK and BANK1 are components of B cells signalosome [2] implicated in the development as well as in the activation and signalling of B cells, respectively [3, 4]. Previous studies have revealed that CD40, BLK and BANK1 genes are involved in the predisposition to several ...

Nov 13th, 2022 - Background/Purpose: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently identified disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Pulmonary involvement has been reported, but a detailed description of lung involvement and radiologic findings is lacking. Methods: A retrospective cohort study was conducted of all patients identified at ...

Nov 13th, 2022 - Background/Purpose: SLE is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased kidney involvement and tissue damage. Whereas some of this variation may be accounted for by environmental and/or socioeconomic factors, the possib...

Nov 13th, 2022 - Background/Purpose: Previous genetic association studies identified a 9 gene region of Xq28 containing IRAK1 as a risk locus for SLE. IRAK1 plays key roles downstream of the endosomal TLRs and IL-1 receptors to activate NF-KB during inflammatory responses. While single nucleotide polymorphisms (SNPs) in IRAK1 have been independently associated with SLE risk, the molecular pathways have not full...

Nov 13th, 2022 - Background/Purpose: An important role of DNA methylation changes in Spondylitis Ankylosing has been recently demonstrated by epigenome-wide studies. However, there is a lack of genome-wide studies that examine the role of epigenetics in the physiopathology of a wider spectrum of Spondyloarthritis and in Psoriatic Arthritis and that further explore its clinical utility. Methods: Here, we measure...

Nov 13th, 2022 - Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease capable of affecting multiple organ systems. Genetic variants in the Human Leukocyte Antigen (HLA) are associated with autoimmune disease, as well as specific autoantibodies in SLE. Yet most studies to date have focused on adults of European ancestry with SLE. We aimed to test the association of HLA variants and spe...

Nov 13th, 2022 - Background/Purpose: Lyn kinase is a member of the Src family of tyrosine kinases that regulates innate and adaptive immune responses. Lyn C-terminal tail tyrosine residue, p.Y508, inactivates wildtype Lyn kinase upon phosphorylation. We describe 3 unrelated patients with de novo LYN mutations affecting p.Y508, whose disease sheds light on the pathogenesis of neutrophilic small vessel vasculitis...

Nov 13th, 2022 - Background/Purpose: Pulmonary arterial hypertension (PAH) is a rare and severe complication of systemic lupus erythematosus (SLE). Human leucocyte antigen (HLA) gene variants in the major histocompatibility complex (MHC) region play key roles in the pathogenesis of SLE. However, the genetic characteristics of HLA in SLE-associated PAH has not been established. In this study, we aimed to identif...