Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.

Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function.

Precision Medicine in Rheumatology: The Promise of Ultrasound-Guided Synovial Biopsy, Barriers to Its Implementation in the United States, and Proposed Solutions.

Purpose Of Review: In the clinical evaluation of inflammatory arthritis and the research into its pathogenesis, there is a growing role for the direct analysis of synovial tissue. Over the years, various biopsy techniques have been used to obtain human synovial tissue samples, and there have been progressive improvements in the safety, tolerability, and utility of the procedure.

Recent Findings: The latest advancement in synovial tissue biopsy techniques is the use of ultrasound imaging to guide the biopsy device, along with evolution in the characteristics of the device itself.

Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis.

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in 'At-Risk' populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48).

Best practices for ultrasound-guided synovial biopsy in the United States.

The target organ in many forms of inflammatory arthritis is the synovium. However, synovial tissue has historically been perceived as either difficult to obtain or of little practical value. Ultrasound-guided synovial biopsy [UGSB] is a safe and well-tolerated bedside procedure that is established in Europe and rapidly growing in popularity in the United States.

Clonal associations of lymphocyte subsets and functional states revealed by single cell antigen receptor profiling of T and B cells in rheumatoid arthritis synovium.

Rheumatoid arthritis (RA) is an autoimmune disease initiated by antigen-specific T cells and B cells, which promote synovial inflammation through a complex set of interactions with innate immune and stromal cells. To better understand the phenotypes and clonal relationships of synovial T and B cells, we performed single-cell RNA and repertoire sequencing on paired synovial tissue and peripheral blood samples from 12 donors with seropositive RA ranging from early to chronic disease. Paired transcriptomic-repertoire analyses highlighted 3 clonally distinct CD4 T cells populations that were enriched in RA synovium: T peripheral helper (Tph) and T follicular helper (Tfh) cells, CCL5+ T cells, and T regulatory cells (Tregs).

Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)HLA-DRA sublining fibroblasts, IL1B pro-inflammatory monocytes, ITGAXTBX21 autoimmune-associated B cells and PDCD1 peripheral helper T (T) cells and follicular helper T (T) cells.

Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.

Objective: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases.

Methods: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment.

Musculoskeletal ultrasound objective structured clinical examination: an assessment of the test.

Objective: To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS).

Methods: A 9-station OSCE was administered to 35 rheumatology fellows trained in MSUS and to 3 expert faculty (controls). Participants were unaware of joint health (5 diseased/4 healthy).

Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor.

Introduction: As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy.

Self-directed learning of basic musculoskeletal ultrasound among rheumatologists in the United States.

Objective: Because musculoskeletal ultrasound (MSUS) is highly user dependent, we aimed to establish whether non-mentored learning of MSUS is sufficient to achieve the same level of diagnostic accuracy and scanning reliability as has been achieved by rheumatologists recognized as international experts in MSUS.

Methods: A group of 8 rheumatologists with more experience in MSUS and 8 rheumatologists with less experience in MSUS participated in an MSUS exercise to assess patients with musculoskeletal abnormalities commonly seen in a rheumatology practice. Patients' established diagnoses were obtained from chart review (gout, osteoarthritis, rotator cuff syndrome, rheumatoid arthritis, and seronegative arthritis).

Severe long-standing dysimmune sensory neuronopathy responsive to etanercept.

Sensory neuronopathy in association with connective tissue disease is a disabling disorder for which there is no well-established therapy. Various immunosuppressive agents, plasmapheresis, and intravenous immunoglobulin have shown only anecdotal or modest beneficial effects. Tumor necrosis factor alpha is a proinflammatory cytokine that mediates TH1-cell inflammatory responses and is a plausible contributor to dorsal root ganglion injury in sensory neuronopathy.

Cardiac tamponade: an uncommon presentation of hypertensive scleroderma renal crisis.

Cardiac tamponade is an extremely rare manifestation of systemic sclerosis and has been reported to be a risk factor for the subsequent development of renal failure. We report the case of a 37-year-old man with recently diagnosed scleroderma who presented with chest pain and shortness of breath. He was found to have scleroderma renal crisis as well as cardiac tamponade.