A5103069704- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Immune Cell Function and Interaction
- Autoimmune and Inflammatory Disorders Research
- Platelet Disorders and Treatments
- Psoriasis: Treatment and Pathogenesis
- Urticaria and Related Conditions
- Single-cell and spatial transcriptomics
- Renal Diseases and Glomerulopathies
- Adrenal Hormones and Disorders
- Asthma and respiratory diseases
- Peripheral Neuropathies and Disorders
- Bone and Joint Diseases
- Reproductive System and Pregnancy
- Osteomyelitis and Bone Disorders Research
- Sarcoidosis and Beryllium Toxicity Research
- Sphingolipid Metabolism and Signaling
- Clinical Reasoning and Diagnostic Skills
- Hospital Admissions and Outcomes
Brigham and Women's Hospital
2010-2024
Harvard University
2006-2024
The University of Texas Southwestern Medical Center
2022
Beth Israel Deaconess Medical Center
2022
Women's Hospital
1991
Beth Israel Deaconess Hospital
1987-1988
Massachusetts General Hospital
1987
Guy's Hospital
1987
Dana-Farber Cancer Institute
1984
Case Western Reserve University
1984
In addition to their pivotal role in thrombosis and wound repair, platelets participate inflammatory responses. We investigated the of autoimmune disease rheumatoid arthritis. identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with arthritis other forms arthritis, but not osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses synovial fibroblasts via interleukin-1. Consistent these...
T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these have traditionally been attributed to CD4 cells, we found that CD8 cells notably abundant in synovium and make more interferon (IFN)-γ nearly as much tumor necrosis factor (TNF) their cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq flow cytometric data, the vast majority synovial tissue fluid belong an effector population characterized by...
Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue receive the drug in long-term prospective study. At 36 months, 16 remained Over this period time, significant improvement was noted number painful and swollen joints, physician patient global assessments, erythrocyte sedimentation rate, prednisone dose. Adverse reactions occurred (62%), including nausea, alopecia, headache, stomatitis, herpes zoster,...
Abstract Twelve patients with active rheumatoid arthritis supplemented their usual diet 20 gm of Max‐EPA fish oil, daily, for 6 weeks. Following this supplementation, the ratio arachidonic acid to eicosapentaenoic in patients' neutrophil cellular lipids decreased from 81:1 2.7:1, and mean generation leukotriene B 4 (with calcium ionophore stimulation) significantly declined by 33%. The chemotaxis both FMLP increased toward normal range at week 6. 5‐lipoxygenase products ionophore‐stimulated...
High-dimensional single-cell analyses have improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or states in patient samples remains challenging because technical and interindividual variation. Here, we present mixed-effects modeling associations single (MASC), a reverse association strategy for testing whether case-control status influences membership any multiple cellular subsets while accounting...
Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with superactivated state in rheumatoid arthritis. We implicated IFN-γ key regulator expression engaging drove strong wave inflammatory cytokine expression. Induction TNF-α after engagement...
Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers anti-GPI antibodies serum many patients with rheumatoid (RA). We evaluated generality these observations cohorts 12 different arthritic and chronic autoimmune diseases...
Abstract Ten patients with rheumatoid arthritis were entered into a 24‐week pilot study of oral cyclosporin A at starting dosage 6 mg/kg/day, followed by 12‐week washout period. Significant improvement in clinical parameters was observed 12 weeks and 24 ( P < 0.02 versus baseline for joint pain swelling indexes patient physician assessments; 0.04 the numbers painful/tender joints swollen joints). Adverse reactions varied: renal impairment occurred all hypertension 7. All demonstrated an...
Abstract Objective To examine rheumatologists' management practices for patients with rheumatoid arthritis (RA) taking glucocorticoids seen at one academic medical rheumatology practice. Methods All diagnosed RA making least 2 visits to the practice who were noted be on an index visit in January or February 1999 included a retrospective chart review. Results Of 623 eligible identified RA, 236 their and this study. The mean daily dosage of prednisone (or its equivalent) was 8.8 mg duration...
Abstract Objective. To compare the cumulative effects of oral methotrexate (MTX) therapy (after 6–8 weeks) with acute (24 hours after a dose) on arachidonic acid metabolism by 5‐lipoxygenase (5‐LO) pathway in neutrophils from patients active rheumatoid arthritis (RA) who were beginning MTX. Methods. Neutrophils and monocytes isolated whole blood 7 RA, immediately before 24 their first weekly dose 7.5 mg MTX, again at weeks. Results. Total immunoreactive leukotriene B 4 (LTB ) formation...
GRAVALLESE, ELLEN M. M.D.; CORSON, JOSEPH COBLYN, JONATHAN S. PINKUS, GERALDINE WEINBLATT, MICHAEL E. M.D. Author Information
Pneumococcal vaccination is important for patients taking immunosuppressive medications, but prior studies suggest that most do not undergo vaccination. The aim of this study was to evaluate the effects a point-of-care paper reminder form as quality improvement (QI) strategy increase numbers immunosuppressed being kept up-to-date with pneumococcal in rheumatology practice.Selected rheumatologists at 5 ambulatory practice sites received be applied who were Interrupted time-series analyses...
Abstract Objective To assess the effectiveness of a multifaceted intervention to improve management glucocorticoid‐induced osteoporosis (GIOP). Methods Of 21 rheumatologists, 11 were randomly assigned 3‐part consisting lecture and discussion regarding optimal GIOP, confidential doctor‐specific audit reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral...
Abstract We studied the effects of a single, oral dose methotrexate (MTX) on arachidonic acid metabolism in neutrophils from 6 patients with rheumatoid arthritis, which were obtained 1 day before and after their usual weekly MTX dose. The had received mean 9.6 mg (range 5–15) for 61.7 months 58–64), none concomitant corticosteroids. Total generation leukotriene B 4 (LTB ) stimulated ex vivo 10 μM calcium ionophore A23187 20 minutes was significantly suppressed, by 53%, compared predose...
SHADICK, NANCY A. M.D., M.P.H.; FANTA, CHRISTOPHER H. M.D.; WEINBLATT, MICHAEL E. O'DONNELL, WALTER COBLYN, JONATHAN S. M.D. Author Information
Objective. The Centers for Disease Control (CDC) recommends pneumococcal vaccination immunocompromised patients. Data suggest that rates of in this population are not optimal. To support continuous quality improvement efforts, we electronically measured status among rheumatology outpatients over time. Methods. Using data from administrative (billing) and electronic health record sources, identified clinic patients seen between 1 February 2008 31 January 2010 prescribed an immunosuppressive...
We report two patients with systemic lupus erythematosus who subsequently developed thrombotic thrombocytopenic purpura. In each case the coexistence of these conditions was confirmed by pathological findings. Both responded to treatment, but one eventually died. A review literature suggests a possible relationship between disorders.
Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed chronic inflammation. A decrease in inflammation patients RA is associated increased low-density lipoprotein (LDL) cholesterol. This study was undertaken prospectively evaluate the changes lipid levels among experiencing and determine association concomitant temporal patterns markers of myocardial injury.A total 196 were evaluated a longitudinal cohort, blood samples...
Abstract Objective Osteoporosis in patients with rheumatoid arthritis (RA) is increasingly recognized as a major comorbidity. We examined past management patterns for glucocorticoid‐induced osteoporosis and attempted to improve care through an educational intervention. The goal was examine the frequency of RA treated at large academic rheumatology practice. Methods performed structured chart review on randomly selected seen during 2004 RA. defined bone mineral density test or receipt...
Abstract In 46 patients with rheumatoid arthritis (RA) the allele C4B*3 occurred in 6 patients, while among 350 normal controls, it times ( P < 0.00002). Among 9 white and 1 black families, each of which had 2 or more members RA, there were 36 haplotypes associated RA. An extended haplotype (specific HLA‐B, DR, complotype significant linkage disequilibrium) containing C4B*3: HLA—‐B15, DR4, BF*S, C2*C, C4A*3, C4B*3, was found twice 0.001) whites disease‐associated chromosomes.
Objective Systemic rheumatic conditions affect reproductive‐aged patients and often require potentially teratogenic medications. We assessed the feasibility impact of a standardized pregnancy intention screening question (One Key Question [OKQ]) in large academic rheumatology practice. Methods This 6‐month pilot quality improvement initiative prompted rheumatologists to ask female aged 18 49 years about their intentions using OKQ. administered surveys assess rheumatologists’ barriers comfort...