Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus.

Introduction: A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22) complementary DNA (cDNA) is associated with an increased risk of systemic lupus erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the expression of PTPN22 differs between healthy individuals and patients with lupus are poorly understood. Our objectives were to identify novel alternatively spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in healthy donors and patients with lupus.

Outcomes in hospitalized pediatric patients with systemic lupus erythematosus.

Objective: Disparities in outcomes among adults with systemic lupus erythematosus (SLE) have been documented. We investigated associations between sociodemographic factors and volume of annual inpatient hospital admissions with hospitalization characteristics and poor outcomes among patients with childhood-onset SLE.

Methods: By using the Pediatric Health Information System, we analyzed admissions for patients aged 3 to <18 years at index admission with ≥ 1 International Classification of Diseases, Ninth Revision code for SLE from January 2006 to September 2011.

Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case-control study.

Introduction: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles.

Methods: We identified 192 women in the Nurses' Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use.

Quality of care for incident lupus nephritis among Medicaid beneficiaries in the United States.

Objective: We investigated the quality of care and factors associated with variations in care among a national cohort of Medicaid enrollees with incident lupus nephritis.

Methods: Using Medicaid Analytic eXtract files from 47 US states and the District of Columbia for 2000-2006, we identified a cohort of individuals with incident lupus nephritis. We assessed performance on 3 measures of health care quality: receipt of immunosuppressive, renal-protective antihypertensive, and antimalarial medications.

Comparison of the 1987 American College of Rheumatology and the 2010 American College of Rheumatology/European League against Rheumatism criteria for classification of rheumatoid arthritis in the Nurses' Health Study cohorts.

Performance of rheumatoid arthritis (RA) classification by the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria, compared to the 1987 ACR criteria, has not been assessed in population-based cohorts in which disease identification is by mailed questionnaire. Women followed in the Nurses' Health Study and Nurses' Health Study II cohorts self-reported new doctor-diagnosed RA on biennial questionnaires. Two RA experts reviewed medical records of 128 new RA self-reports to obtain individual 1987 and 2010 criteria and arrived at a consensus opinion.

The association between silica exposure and development of ANCA-associated vasculitis: systematic review and meta-analysis.

Background: Crystalline silica is among the environmental exposures associated with increased risk of autoimmune diseases, including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. Silica exposure has also been related to the development of ANCA-associated vasculitides (AAV), but past studies appear to conflict as to the presence and magnitude of the associated risks of disease. We aimed to conduct a systematic review of the existing studies and meta-analysis of their results.

Sexual disparities in the incidence and course of SLE and RA.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) disproportionately affect females compared to males, with female to male prevalence ratios of 7-9:1 for SLE and 2-3:1 for RA. Interestingly, epidemiologic studies indicate that men that develop SLE may have more morbidity than women, but the same is not true for RA. Given the sex and age bias of SLE and RA, sex hormones may influence the pathogenesis of these diseases.

Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus.

Background: Cutaneous discoid lupus erythematosus (DLE) among patients with systemic lupus erythematosus (SLE) may be associated with less severe disease and with low frequency of nephritis and end-stage renal disease (ESRD).

Objective: We sought to investigate associations between confirmed DLE and other SLE manifestations, adjusting for confounders.

Methods: We identified patients with rheumatologist confirmation, according to 1997 American College of Rheumatology (ACR) SLE classification criteria, more than 2 visits, longer than 3 months of follow-up, and documented year of SLE diagnosis.

Sex-specific environmental influences on the development of autoimmune diseases.

Sex differences in autoimmune diseases are evolutionarily tied to the fact that the female immune system is confronted with intense alterations during menstrual cycles, pregnancy and childbirth. These events may be associated with breaches in the mucosal epithelial layers that are shielding us from environmental factors. Associations between environmental agents and autoimmune diseases have been described extensively in prior studies.

Association of environmental and genetic factors and gene-environment interactions with risk of developing rheumatoid arthritis.

Objective: We developed rheumatoid arthritis (RA) risk models based on validated environmental factors (E), genetic risk scores (GRS), and gene-environment interactions (GEI) to identify factors that can improve accuracy and reclassification.

Methods: Models including E, GRS, and GEI were developed among 317 white seropositive RA cases and 551 controls from the Nurses' Health Studies (NHS) and validated in 987 white anti-citrullinated protein antibody-positive cases and 958 controls from the Swedish Epidemiologic Investigation of Rheumatoid Arthritis (EIRA), stratified by sex. Primary analyses included age, smoking, alcohol, parity, weighted GRS using 31 non-HLA alleles and 8 HLA-DRB1 alleles, and the HLA × smoking interaction.

The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review.

Objective: To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE.

Methods: We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data.

Ambient air pollution exposures and risk of rheumatoid arthritis.

Objective: Environmental factors may play a role in the development of rheumatoid arthritis (RA). We previously observed increased RA risk among women living closer to major roads (a source of air pollution). Herein, we examined whether long-term exposures to specific air pollutants were associated with RA risk among women in the Nurses' Health Study (NHS).

Exposure to ultraviolet-B and risk of developing rheumatoid arthritis among women in the Nurses' Health Study.

Objective: To examine the association between ultraviolet-B (UV-B) light exposure and rheumatoid arthritis (RA) risk among women in two large prospective cohort studies, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII).

Methods: A total of 106 368 women from NHS, aged 30-55 years in 1976, and 115 561 women from NHSII, aged 25-42 in 1989, were included in the analysis. We identified women with incident RA from the start of each cohort until 2008 (NHS) and 2009 (NHSII).

Lymphoma risk in systemic lupus: effects of disease activity versus treatment.

Objective: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).

Methods: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages.

Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004.

Objective: Systemic lupus erythematosus (SLE) and lupus nephritis (LN) disproportionately affect individuals who are members of racial/ethnic minority groups and individuals of lower socioeconomic status (SES). This study was undertaken to investigate the epidemiology and sociodemographics of SLE and LN in the low-income US Medicaid population.

Methods: We utilized Medicaid Analytic eXtract data, with billing claims from 47 states and Washington, DC, for 23.

Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

Objective: To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population.

Methods: Children ages 3 years to <18 years with a diagnosis of SLE (defined as ≥3 claims with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004.

Ambient air pollution exposures and risk of rheumatoid arthritis: results from the Swedish EIRA case-control study.

Objective: Environmental factors may play a role in the development of rheumatoid arthritis (RA). We examined whether long-term exposures to air pollution were associated with the risk of RA in the Swedish Epidemiological Investigation of Rheumatoid Arthritis Study.

Methods: We studied 1497 incident RA cases and 2536 controls.

Dietary intake of vitamin D during adolescence and risk of adult-onset systemic lupus erythematosus and rheumatoid arthritis.

Objective: Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult-onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII).

Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.

Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations.

Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus.

Objective: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have fewer children on average than other women. We sought to determine the roles of infertility, pregnancy loss, and personal choice on family size in women with these diseases.

Methods: A reproductive history questionnaire was completed by women with RA and SLE participating in a longitudinal observational study.

Variation in initial kidney replacement therapy for end-stage renal disease due to lupus nephritis in the United States.

Objective: Little is known about the patterns of use of initial kidney replacement therapies among patients with lupus nephritis (LN) end-stage renal disease (ESRD). We aimed to identify sociodemographic and clinical factors associated with variation in initial kidney replacement therapies among LN ESRD patients.

Methods: Patients with incident LN ESRD (1995-2006) were identified in the US Renal Data System.

Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases?

Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and inflammatory bowel disease, have complex pathogeneses and likely multifactorial etiologies. The current paradigm for understanding their development is that the disease is triggered in genetically-susceptible individuals by exposure to environmental factors. Some of these environmental factors have been specifically identified, while others are hypothesized and not yet proven, and it is likely that most have yet to be identified.

Epstein-Barr virus serologic abnormalities and risk of rheumatoid arthritis among women.

Background: Epstein-Barr virus (EBV) infection and the immune response may be involved in the pathogenesis of rheumatoid arthritis (RA). Past studies have suggested an association between EBV and RA.

Methods: We studied the association between EBV serologies and RA risk in a nested case-control study in the Nurses' Health Study (NHS) cohorts.

Genetic risk score predicting risk of rheumatoid arthritis phenotypes and age of symptom onset.

Background: Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the impact of 39 validated genetic risk alleles on the risk of RA phenotypes characterized by serologic and erosive status.

Methods/principal Findings: We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human Leukocyte Antigen alleles among 542 Caucasian RA cases and 551 Caucasian controls from Nurses' Health Study and Nurses' Health Study II.