Factors associated with arterial vascular events in PROFILE: a Multiethnic Lupus Cohort.

The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients (n = 1333) of defined ethnicity from five different US institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene.

Subtypes of HLA-B27: history and implications in the pathogenesis of ankylosing spondylitis.

HLA-B27 represents a family of 38 closely related cell surface proteins (encoded by the alleles HLA-B*2701-39) called subtypes of HLA-B27, most of which have evolved from the ubiquitous HLA-B*2705 (specifically the B*27052 allele). HLA-B27 subtypes are largely characterized by nucleotide substitutions (mostly nonsynonymous) in exons 2 and 3 which encode alpha1 and alpha2 domains ofthe peptide binding groove respectively. Table 1 shows the description of sequences of HLA-B27 allele sequences.

Impact of immigration on the clinical expression of systemic lupus erythematosus: a comparative study of Hispanic patients residing in the USA and Mexico.

Objective: To compare the socio-economic characteristics, clinical features and health-related quality of life in Hispanic SLE patients residing in Mexico and in the Southwest USA (Mexican and Texan, herein).

Methods: Mexican and Texan SLE patients (fulfilling ACR criteria) participating in separate longitudinal outcome studies were evaluated. Texan patients were randomly chosen to match total disease duration with the Mexican patients.

Disease activity and damage are not associated with increased levels of fatigue in systemic lupus erythematosus patients from a multiethnic cohort: LXVII.

Objective: To determine the factors associated with increased levels of fatigue over the course of the disease in systemic lupus erythematosus (SLE) patients from LUpus in MInorities: NAture versus nurture, a longitudinal multiethnic cohort.

Methods: Patients with SLE (according to the American College of Rheumatology revised and updated criteria) age >/=16 years with a disease duration View Article and Find Full Text PDF

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

Objective: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US.

Methods: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays.

A polymorphism within IL21R confers risk for systemic lupus erythematosus.

Objective: Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL-21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE.

Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls.

Objective: To determine human leucocyte antigen-class II (HLA-class II) (DRB1, DQB1, DQA1 and DPB1) alleles, haplotypes and shared epitopes associated with scleroderma (systemic sclerosis (SSc)) and its subphenotypes in a large multi-ethnic US cohort by a case-control association study.

Patients And Methods: 1300 SSc cases (961 white, 178 black and 161 Hispanic subjects) characterised for clinical skin forms (limited vs diffuse), SSc-specific autoantibodies (anticentromere (ACA), anti-topoisomerase I (ATA), anti-RNA polymerase III (ARA), anti-U3 ribonucleoprotein (fibrillarin)) and others were studied using molecular genotyping. Statistical analyses in SSc itself by ethnicity, gender, skin type and autoantibodies were performed using exact logistic regression modelling for dominant, additive and recessive effects from HLA.

Gene and pathway-based second-wave analysis of genome-wide association studies.

Despite the great success of genome-wide association studies (GWAS) in identification of the common genetic variants associated with complex diseases, the current GWAS have focused on single-SNP analysis. However, single-SNP analysis often identifies only a few of the most significant SNPs that account for a small proportion of the genetic variants and offers only a limited understanding of complex diseases. To overcome these limitations, we propose gene and pathway-based association analysis as a new paradigm for GWAS.

Time to neuropsychiatric damage occurrence in LUMINA (LXVI): a multi-ethnic lupus cohort.

The aims of this study were to examine the predictors of time to neuropsychiatric (NP) damage and its impact on mortality in 632 systemic lupus erythematosus African-American, Hispanic and Caucasian LUpus in MInorities: NAture versus Nurture (LUMINA) patients, age >or= 16 years and disease duration View Article and Find Full Text PDF

Entheses and bones in spondyloarthritis: 2008 Annual Research and Education Meeting of the Spondyloarthritis Research and Therapy Network (SPARTAN).

The Spondyloarthritis Research and Therapy Network (SPARTAN), founded in 2003 to promote research, education, and treatment of ankylosing spondylitis (AS) and related forms of spondyloarthritis (SpA), held its 6th Annual Research and Education Meeting in July 2008 in Cleveland, Ohio, USA. The overall theme of the meeting was entheses and bones in SpA, which included presentations on the anatomy and physiology of the synovial-entheseal complex; bone formation and destruction, and the effect of inflammation on bone; the Th17 axis, HLA-B27, IL23R, and ARTS1; and breakout sessions on epidemiology and registries.

Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis.

Objective: To improve prognostic ability in ankylosing spondylitis (AS), we sought to identify demographic, clinical, and immunogenetic characteristics associated with radiographic severity in a large cohort of patients.

Methods: Patients with AS for > or =20 years were enrolled in a cross-sectional study (n = 398). Pelvic and spinal radiographs were scored using the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), and radiographic severity was measured as the BASRI-s/duration of AS.

Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort.

Objective: To assess whether hydroxychloroquine can delay renal damage development in lupus nephritis patients.

Methods: Lupus nephritis patients (n = 256) from the LUpus in MInorities, NAture versus nurture study (n = 635), a multiethnic cohort of African Americans, Hispanics, and Caucasians, age > or =16 years with disease duration < or =5 years at baseline (T0) were studied. Renal damage was defined using the Systemic Lupus International Collaborating Clinics Damage Index (> or =1 of the following lasting at least 6 months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria > or =3.

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort.

Objective: To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE.

Methods: SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration View Article and Find Full Text PDF

Rheumatic manifestations associated with HIV in the highly active antiretroviral therapy era.

Purpose Of Review: To evaluate the rheumatic manifestations associated with HIV infection in the highly active antiretroviral therapy (HAART) era.

Recent Findings: The overall prevalence of rheumatic manifestations in HIV population is approximately 9% with various clinical features. Anti-TNF agents do not appear to adversely affect the CD4 cell counts or viral load if the HIV infection is well controlled prior to initiation of therapy.

Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis.

Objectives: To assess whether there is excess transmission of alleles from the ERAP1 ERAP2 locus in families with ankylosing spondylitis (AS).

Methods: 199 multiplex families with AS with four non-synonymous single nucleotide polymorphisms (SNPs), three in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs27044, rs10050860 and rs30187) and one in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782), were genotyped and family-based association analyses were performed.

Results: Family-based association testing (FBAT -e; empirical variance option) analysis showed that ERAP1 rs30187[T] was associated with AS (additive model: p=0.

Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing.

Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls.

Genetic associations of LYN with systemic lupus erythematosus.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.

Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population.

Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients.

Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus.

Objective: Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype.

Methods: We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent.

Factors predictive of overall health over the course of the disease in patients with systemic lupus erythematosus from the LUMINA cohort (LXII): use of the SF-6D.

Objective: Health related quality of life (HRQOL) over course of the disease was ascertained in SLE patients from LUMINA, a multiethnic US cohort, using the SF-36-derived utility measure, the SF-6D.

Methods: All available visits were examined to predict HRQOL using either variables from the baseline or enrollment visits or from the preceding visits. The physical and mental component summary (PCS and MCS, respectively) measures of the SF-36 were also examined.

Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort.

Objective: Damage accrual in SLE has been previously shown to be an independent predictor of mortality. We sought to discern which SLICC Damage Index (SDI) domains are the most important predictors of survival in SLE.

Methods: SLE patients (ACR criteria), age > or =16 years, disease duration < or =5 years at enrolment, of African-American, Hispanic or Caucasian ethnicity were studied.

Spondyloarthritis: clinical suspicion, diagnosis, and sports.

Spondyloarthritis (SpA), a family of inflammatory back diseases including ankylosing spondylitis, is an important and under-recognized cause of chronic back pain in younger patients who are likely to participate in sports and athletic activities. These diseases are characterized by the presence of inflammatory back pain--lumbar or buttock/hip pain lasting longer than 3 months associated with improvement with activity, worsening with rest, relief with non-steroidal anti-inflammatory drugs (NSAIDs), and morning stiffness lasting longer than 30 min. There are also characteristic radiographic findings involving the sacroiliac joints, vertebrae, and in certain diseases, the peripheral joints.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): LXI. Value of C-reactive protein as a marker of disease activity and damage.

Objective: To determine whether C-reactive protein (CRP) measured by a high sensitivity (hs) assay is a surrogate marker of disease activity and damage in systemic lupus erythematosus (SLE).

Methods: Five hundred eighty-eight patients with SLE participating in a multiethnic cohort (Hispanic, African American, and Caucasian) were studied. Disease activity was measured with the Systemic Lupus Activity Measure-Revised (SLAM-R) and damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI).