Bank1 modulates the differentiation and molecular profile of key B cell populations in autoimmunity.

This study aimed at defining the role of the B cell adaptor protein BANK1 in the appearance of age-associated B cells (ABCs) in 2 SLE mouse models (TLR7.tg6 and imiquimod-induced mice), crossed with Bank1-/- mice. The absence of Bank1 led to a significant reduction in ABC levels, also affecting other B cell populations.

Variants in the autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including .

Molecular subtypes explain lupus epigenomic heterogeneity unveiling new regulatory genetic risk variants.

The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood DNA methylation from 213 SLE patients and 221 controls.

Exploring the contribution of genetics on the clinical manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by diverse clinical manifestations affecting multiple organs and systems. The understanding of genetic factors underlying the various manifestations of SLE has evolved considerably in recent years. This review provides an overview of the genetic implications in some of the most prevalent manifestations of SLE, including renal involvement, neuropsychiatric, cutaneous, constitutional, musculoskeletal, and cardiovascular manifestations.

Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis.

Introduction: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options.

Methods: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN ( = 41) and active nonrenal lupus ( = 62) versus healthy controls (HCs) ( = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery ( = 26) and a replication ( = 15) set of active LN cases.

Results: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis.

Classification of systemic lupus erythematosus: From the development of classification criteria to a new taxonomy?

SLE is a highly variable systemic autoimmune disease. Its immunopathological effector phase is partly understood. However, the background of its variability is not.

A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome.

Objectives: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.

Methods: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry.

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort.

Objectives: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).

Methods: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission.

Results: We analysed data from 321 patients; 40.

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI).

Serum profiling identifies CCL8, CXCL13, and IL-1RA as markers of active disease in patients with systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).

Methods: Serum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121).

Local Ancestry at the Major Histocompatibility Complex Region is Not a Major Contributor to Disease Heterogeneity in a Multiethnic Lupus Cohort.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies.

Methods: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array.

Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs).

The improved understanding of the molecular basis of innate immunity have led to the identification of type I interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of several Immune-mediated inflammatory diseases (IMIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjögren's syndrome. Here, we review the main data regarding the opportunity to target type I IFNs for the treatment of IMIDs. Type I IFNs and their downstream pathways can be targeted pharmacologically in several manners.

Gut epithelial barrier dysfunction in lupus triggers a differential humoral response against gut commensals.

Introduction: Systemic lupus erythematosus is an autoimmune disease with multisystemic involvement including intestinal inflammation. Lupus-associated intestinal inflammation may alter the mucosal barrier where millions of commensals have a dynamic and selective interaction with the host immune system. Here, we investigated the consequences of the intestinal inflammation in a TLR7-mediated lupus model.