Objective. The Manhattan Lupus Surveillance Program (MLSP) is a population-based registry designed to determine the prevalence of systemic lupus erythematosus (SLE) in 2007 and the incidence from 2007 to 2009 among residents of New York County (Manhattan), New York, and to characterize cases by race/ethnicity, including Asians and Hispanics, for whom data are lacking.Methods. We identified possible SLE cases from hospital records, rheumatologist records, and administrative databases. Cases were defined according to the American College of Rheumatology (ACR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, or the treating rheumatologist's diagnosis. Rates among Manhattan residents were age-standardized, and capture-recapture analyses were conducted to assess case underascertainment.Results. By the ACR definition, the agestandardized prevalence and incidence rates of SLE were 62.2 and 4.6 per 100,000 person-years, respectively. Rates were~9 times higher in women than in men for prevalence (107.4 versus 12.5) and incidence (7.9 versus 1.0). Compared with non-Hispanic white women (64.3), prevalence was higher among non-Hispanic black (210.9), Hispanic (138.3), and non-Hispanic Asian (91.2) women. Incidence rates were higher among non-Hispanic black women (15.7) compared with non-Hispanic Asian (6.6), Hispanic (6.5), and non-Hispanic white (6.5) women. Capture-recapture adjustment increased the prevalence and incidence rates (75.9 and 6.0, respectively). Alternate SLE definitions without capture-recapture adjustment revealed higher age-standardized prevalence and incidence rates (73.8 and 6.2, respectively, by the SLICC definition and 72.6 and 5.0 by the rheumatologist definition) than the ACR definition, with similar patterns by sex and race/ethnicity.Conclusion. The MLSP confirms findings from other registries on disparities by sex and race/ethnicity, provides new estimates among Asians and Hispanics, and provides estimates using the SLICC criteria.Systemic lupus erythematosus (SLE) is a potentially fatal, heterogeneous, chronic, systemic autoimmune disease of unknown etiology (1). Given widely The views expressed herein are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Objective To better define the immunologic character of the T cell infiltrate in lupus nephritis. Methods We performed double immunohistochemical staining and clonotypic T cell receptor (TCR) beta-chain sequencing in multiple anatomic regions isolated by laser-capture microdissection from renal biopsies. Results SLE kidneys have a variably patterned and often extensive infiltrate of predominantly clonally expanded T cells of CD4 and CD8 lineages. CD4 T cells were prominent in nearly two-thirds of SLE biopsies, and distributed as broad periglomerular aggregates or intermixed with CD8 T cells forming periglomerular caps. Sequencing of the T cell TCR from periglomerular regions showed a predominance of clonally expanded T cells. The CD8 T cells, which were present in all biopsies, often adhered to Bowman's capsule and infiltrated the tubular epithelium. They exhibited features that suggest participation in an adaptive immune response: differentiation into CD28null memory-effector phenotype, trafficking of the same expanded clonotype to different regions of the kidney and to the peripheral blood, and clonal persistence for years in repeat biopsies. CD8 T cell tubulitis was especially associated with progressive changes. Conclusions The immunological characteristics of the infiltrating CD4 and CD8 T cells in the lupus kidney indicate they have the potential to mediate injury, which may be relevant to development of progressive renal failure. Whereas the oligoclonality of the CD4 T cell infiltrate is consistent with the paradigm of SLE as a class II-associated autoimmune disease, the finding of CD8 T cell clonality and trafficking implies participation in a distinct systemic adaptive immune response.

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Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges in RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete disease remission, and lack of a cure. We profiled the full spectrum of cells in inflamed synovium from patients with RA with the goal of deconstructing the cell states and pathways characterizing pathogenic heterogeneity in RA. Our multicenter consortium effort used multi-modal CITE-seq, RNA-seq, and histology of synovial tissue from 79 donors to build a >314,000 single-cell RA synovial cell atlas with 77 cell states from T, B/plasma, natural killer, myeloid, stromal, and endothelial cells. We stratified tissue samples into six distinct cell type abundance phenotypes (CTAPs) individually enriched for specific cell states. These CTAPs demonstrate the striking diversity of RA synovial inflammation, ranging from marked enrichment of T and B cells (CTAP-TB) to a congregation of specific myeloid, fibroblast, and endothelial cells largely lacking lymphocytes (CTAP-EFM). Disease-relevant cytokines, histology, and serology metrics are associated with certain CTAPs. This comprehensive RA synovial atlas and molecular, tissue-based CTAP stratification reveal new insights into RA pathology and heterogeneity, which could lead to novel targeted-treatment approaches in RA.

Rheumatoid arthritis (RA) patients have a 50% increased risk of cardiovascular (CV)-related morbidity and mortality. This excess CV risk is closely linked to RA disease severity and chronic inflammation, hence is largely underestimated by traditional risk calculators such as the Framingham Risk Score. Epidemiological studies have shown that patients with RA are more likely to have silent ischemic heart disease, develop heart failure, and experience sudden death compared with controls. Elevations in pro-inflammatory cytokines, circulating autoantibodies, and specific T cell subsets, are believed to drive these findings by promoting atherosclerotic plaque formation and cardiac remodeling. Current European League Against Rheumatism (EULAR) guidelines state that rheumatologists are responsible for the assessment and coordination of CV disease (CVD) risk management in patients with RA, yet the optimal means to do so remain unclear. While these guidelines focus on disease activity control to mitigate excess CV risk, rather than providing a precise algorithm for choice of therapy, studies suggest a differential impact on CV risk of nonbiologic disease-modifying anti-rheumatic drugs (DMARDs), biologic DMARDs, and small molecule-based therapy. In this review, we explore the mechanisms linking the pathophysiologic intrinsic features of RA with the increased CVD risk in this population, and the impact of different RA therapies on CV outcomes.

Performance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high-quality samples for research. Through the use of cutting-edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine-based approach for patients with RA is attainable.

Objectives Hydroxychloroquine (HCQ) is a key therapy in systemic lupus erythematosus (SLE). Medication non-adherence is reported in up to 80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the role of HCQ level measurement in routine clinical care and its association with disease activity in a predominantly Hispanic population. Methods SLE patients from the Columbia University Lupus cohort treated with HCQ for ≥ 6 months and reporting medication adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as an HCQ level <500 ng/ml. The association between HCQ levels and disease activity measured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was evaluated. Results One hundred and eight patients were enrolled; the median age was 38 years, 91% were female, and 63% were Hispanic. The median SLEDAI-2K was 4.3 (0–20). Forty-one percent of patients had an HCQ level <500 ng/ml consistent with non-adherence, of which 19% had undetectable levels. A higher SLEDAI-2K score was associated with low HCQ levels ( p = 0.003). This association remained significant after adjusting for depression ( p = 0.0007). Conclusion HCQ levels < 500 ng/ml were associated with higher disease activity and accounted for 32% of the SLEDAI-2K variability. HCQ blood measurement is a simple and reliable method to evaluate medication adherence in SLE. Reasons for non-adherence (levels < 500 ng/ml) should be further explored and addressed.

ObjectivesCardiovascular disease (CVD) is a leading cause of death in systemic lupus erythematosus (SLE) and in rheumatoid arthritis (RA). Although only explored in one study, ECG non-specific ST-T abnormalities, in addition to corrected QT-interval (QTc) prolongation, were recently reported in an SLE inception cohort. Importantly, these ECG abnormalities are known predictors of CVD mortality in the general population, yet their prevalence in patients with established SLE has not been evaluated.MethodsWe cross-sectionally investigated the presence of non-specific ST-T and QTc abnormalities in 50 patients with SLE, predominantly Hispanic and black, without CVD or SLE-related cardiac involvement and compared them with 139 patients with RA without CVD. Demographics, disease-specific characteristics and CVD risk factors were ascertained and adjusted for.ResultsPatients with SLE (mean age 36±13 years, 92% women, 6 years median disease duration, 96% Hispanics and blacks) had a 3.3-fold higher adjusted prevalence of non-specific ST-T abnormalities (56% vs 17%; p <0.0001) compared with RA, despite the older age and higher percentage of men in the RA group. The QTc was 26 ms longer in SLE compared with RA (p=0.002) in the setting of a higher percentage of women, blacks, Hispanics and higher C reactive protein levels in the SLE group.ConclusionsThis study demonstrates a high prevalence of ECG abnormalities in predominantly Hispanic and black patients with SLE. Longitudinal evaluation of the progression to potentially life-threatening arrhythmias and/or cardiovascular events is warranted.