Mapping Monocyte States in Class IV Human Lupus Nephritis

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Paul J. Hoover, MD, PhD

Prior work in Lupus Nephritis has shown that immune cell infiltration, especially that of monocytes, is associated with pathologic tissue remodeling and declining renal function. A deeper understanding of infiltrating monocytes could yield more accurate interpretations of histopathologic lesions, better disease predictors, and new therapeutic concepts. Newer technologies offer a promising path toward this goal. Single cell-RNA sequencing (scRNA-seq) enables the molecular classification of cell states based on the expression of thousands of genes, and multiplex-immunofluorescent imaging enables precise spatial localization of these cell states in the context of diseased tissue. Groundwork to merge these technologies derives from our work with the Accelerating Medicines Partnership (AMP) consortium.
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Elucidating the Biology and Role of Synovial Fibroblasts in Rheumatoid Arthritis

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Kevin S. Wei, MD, PhD

Synovial fibroblasts are mesenchymal cells in the synovium that regulate tissue homeostasis in healthy joints. However, in rheumatoid arthritis (RA), synovial fibroblasts assume pathological functions as they recruit infiltrating immune cells that degrade cartilage and bone, leading to joint damage.  Therapies aimed at synovial fibroblasts in RA have the theoretical potential to prevent joint damage while sparing side-effects from immunosuppression. However, incomplete understanding of synovial fibroblast heterogeneity and the pathways that regulate their identity pose major challenges to the therapeutic targeting of these cells.  We sought to attack this problem by applying cutting-edge single cell technology to examine the biology of synovial fibroblasts in RA.
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Development of a Set of Potentially Preventable Adverse Conditions Specific to Lupus: A Delphi Consensus Study

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Candace H. Feldman, MD, MPH, ScD

It is estimated that at least 25 percent of all individuals with lupus are hospitalized each year. These hospitalizations tend to be associated with significant morbidity and mortality and are costly for the health care system. The U.S. Agency for Healthcare Research and Quality (AHRQ) developed a set of prevention quality indicators which they defined as conditions that “should be treatable on an outpatient basis, or that could be less severe if treated early and appropriately.” The AHRQ has used this set of “ambulatory care sensitive conditions” to identify populations at risk for hospitalization and to better understand the breakdown of health care services for these vulnerable groups. Examples of these conditions include diabetic complications, pulmonary disease (e.g. asthma) exacerbations, and pyelonephritis.
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Abdominal Obesity and Risk of Developing Rheumatoid Arthritis in Women

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Bing Lu, MD, DrPH

Individuals with obesity, particularly abdominal obesity, are at an increased risk of hypertension, dyslipidemia, diabetes, coronary heart disease, stroke, cancer, and all-cause mortality. Several studies have observed an association between obesity and increased risk of rheumatoid arthritis (RA). Abdominal obesity is associated with visceral fat and has been a stronger predictor of obesity-related health risk, such as cardiovascular disease, than overall obesity as measured by BMI. We sought to investigate whether abdominal obesity per se predicts RA risk in two large prospective cohorts, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).
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Metabolic Pathways in Monocyte Development Identified Using HoxB8 Model Cells

Metabolism is a hot topic in immunology. Immune cells carry out diverse functions by exploiting different pathways of taking in nutrients and generating energy. Accordingly, metabolic processes such as glycolysis and oxidative phosphorylation are now front and center in understanding how cells behave in the context of normal and pathogenic immune responses. Read More

Using CyTOF Mass Cytometry and RNA-seq to Identify New Cell Populations in Arthritis

The inflamed joint is a complex place. Many different types of cells must interact with each other to initiate and sustain inflammation and tissue injury. These include both those resident in the joint before inflammation started and cells that were recruited or developed later. To get a handle on this complexity, investigators need methods that can provide highly detailed portraits of individual cells. A major goal of the Joint Biology Consortium’s Cellular Systems Core, directed by Dr. Jim Lederer, is to accelerate research by JBC members through two such methods: cytometry by time of flight (CyTOF) mass cytometry and RNA sequencing (RNA-seq). Read More

Human Subject Recruitment via JBC is Helping to Unravel Role of PTPN22 in RA Development

A single genetic variant in PTPN22 has been known for over a decade to convey risk for rheumatoid arthritis (RA), but exactly how remains a mystery. Led by rheumatologist and researcher Dr. I-Cheng Ho, investigators at BWH are using the JBC to understand PTPN22 as a regulator of citrullination, the post-translational protein modification of arginine that plays a leading role in RA biology.   Read More

The Joint Biology Consortium: A New Resource for Translational Research in Rheumatology

Conducting high-quality translational research in rheumatology is increasingly difficult. Major projects often require a range of methods, from patient recruitment to cutting-edge ‘omics technologies to big-data bioinformatics. Most research groups lack the expertise to cover this range, and so must either limit the scope of their work or expend substantial effort working outside their “comfort zone” to achieve their research goals. Neither of these options efficiently advances the science of rheumatology.

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Exercise enhancement among Rheumatoid Arthritis patients: Research from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study

Iverson MD, Frits M, von Heideken J, Weinblatt M, Shadick NA.  Physical activity and correlates of physical activity participation over three years in adults with rheumatoid arthritis.  Arthritis Care Res (Hoboken) 2017;69(10):1535-1545. PMCID:PMC5436948

The Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) was founded 14 years ago by Drs. Nancy A. Shadick and Michael Weinblatt to study genetic and clinical predictors of disease activity, biomarkers of disease response, and the natural history of patients with rheumatoid arthritis (RA) treated in the biologic DMARD era. Over 1,400 patients with either new onset or established RA disease have been recruited from the practices of Brigham and Women’s Hospital rheumatologists.  At annual visits, information is collected on multiple variables, including demographics, disease activity score (DAS), medication use, co-morbidities, and functional status. More than 1,200 clinical variables are collected at each six month timepoint, which allows for the generation of extensive phenotyping and clinical analyses.

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Over 40 Years of Rheumatology Clinical Research at Brigham and Women’s Hospital

Brigham and Women’s Hospital Division of Rheumatology, Immunology and Allergy

In 1977, Dr. Matthew Liang founded the clinical research group in rheumatology at Brigham and Women’s Hospital (BWH).  The original funding for this group derived from the NIH Multipurpose Arthritis Center program.  Dr. Lawren Daltroy, a behavioral scientist, joined Dr Liang in 1982, and they pursued several innovative behavioral trials focusing on lupus, back pain, and Lyme disease. The faculty grew during the 1980s and 1990s with the addition of Drs. Jeffrey Katz, Nancy Shadick, and Elizabeth Karlson.

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