Dataset Information

MHC associations with clinical and autoantibody manifestations in European SLE.

ABSTRACT: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.

SUBMITTER: Morris DL

PROVIDER: S-EPMC4102853 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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MHC associations with clinical and autoantibody manifestations in European SLE.

Morris D L DL Fernando M M A MM Taylor K E KE Chung S A SA Nititham J J Alarcón-Riquelme M E ME Barcellos L F LF Behrens T W TW Cotsapas C C Gaffney P M PM Graham R R RR Pons-Estel B A BA Gregersen P K PK Harley J B JB Hauser S L SL Hom G G Langefeld C D CD Noble J A JA Rioux J D JD Seldin M F MF Vyse T J TJ Criswell L A LA

Genes and immunity 20140306 4

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes ...[more]

PMID: 24598797

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Project description:To investigate brain perfusion patterns in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE and non-NPSLE, respectively) and to identify biomarkers for the diagnosis of NPSLE using noninvasive three-dimensional (3D) arterial spin labeling (ASL). Thirty-one NPSLE and 24 non-NPSLE patients and 32 age- and sex-matched normal controls (NCs) were recruited. Three-dimensional ASL-MRI was applied to quantify cerebral perfusion. Whole brain, gray (GM) and white matter (WM), and voxel-based analysis (VBA) were performed to explore perfusion characteristics. Correlation analysis was performed to find the relationship between the perfusion measures, lesion volumes, and clinical variables. Receiver operating characteristic (ROC) analysis and support vector machine (SVM) classification were applied to differentiate NPSLE patients from non-NPSLE patients and healthy controls. Compared to NCs, NPSLE patients showed increased cerebral blood flow (CBF) within WM but decreased CBF within GM, while non-NPSLE patients showed increased CBF within both GM and WM. Compared to non-NPSLE patients, NPSLE patients showed significantly reduced CBF in the frontal gyrus, cerebellum, and corpus callosum. CBF within several brain regions such as cingulate and corpus callosum showed significant correlations with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index scores. ROC analysis showed moderate performance in distinguishing NPSLE from non-NPSLE patients with AUCs > 0.7, while SVM analysis demonstrated that CBF within the corpus callosum achieved an accuracy of 83.6% in distinguishing NPSLE from non-NPSLE patients. Different brain perfusion patterns were observed between NPSLE and non-NPSLE patients. CBF measured by noninvasive 3D ASL could be a useful biomarker for the diagnosis and disease monitoring of NPSLE and non-NPSLE patients.

Dataset Information

MHC associations with clinical and autoantibody manifestations in European SLE.

Publications

MHC associations with clinical and autoantibody manifestations in European SLE.

Similar Datasets

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