The latest medical research on Rheumatology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.

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Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases.

Nature Reviews Rheumatology

Organ fibrosis is a lethal outcome of autoimmune rheumatic diseases such as systemic sclerosis. Myofibroblasts are scar-forming cells that are ulti...

Tuberculosis in biologic users for rheumatic diseases: results from the South African Biologics Registry (SABIO).

Annals of the Rheumatic Diseases

To evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome.

TB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical companies. Demographics, LTBI screening and treatment, biological and disease modifying antirheumatic drug (DMARD) therapies, TB diagnosis and outcomes were recorded.

96 TB cases were collected from 1999 to June 2017: rheumatoid arthritis 55, ankylosing spondylitis 27, psoriatic arthritis 4, and juvenile inflammatory arthritis 10. The TB rate was 1240/100 000 person years for biologic users (n=96) versus the biologic naive cohort of 0/100 000 years with an incidence rate difference of 0.0124 (p<0.0001). 60/96 had pulmonary and 36/96 had extra-pulmonary TB. Reactivation TB occurred in 45/96 cases. TB occurred in all biologics licenced in South Africa, the majority in monoclonal inhibitors (1683/100 000 person years) compared with etanercept (861/100 000 person years) and non-tumour necrosis factor (TNF) inhibitors (681/100 000 person years). The incidence rate ratio for monoclonal inhibitors compared with etanercept was 1.96 (p=0.005) and 2.47 (p=0.002) compared with non-TNF inhibitors with no significant difference between non-TNF inhibitors and etanercept (p=0.336). From those (12.9%) who screened LTBI positive, 14 developed TB, while the majority (77) screened LTBI negative. Black race, male sex, younger age and residence in the Western Cape were statistical risk factors. Two drug resistant TB cases and six deaths occurred.

Reactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.

The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease.

Arthritis Rheumatol

IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD.

An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included.

A 3-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI] 97.2-99.8%) and a sensitivity of 85.5% (95% CI 81.9-88.5%). In the second, the specificity was 97.8% (95% CI 93.7-99.2%) and the sensitivity was 82.0% (95% CI 77.0-86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds.

ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.

Family history of rheumatologic, autoimmune, and non-autoimmune diseases and risk of rheumatoid arthritis.

Arthritis Care Res

Since comorbidities such as autoimmune diseases may be associated with RA risk, we hypothesized that family history of these other conditions might also predict RA. Therefore, we aimed to determine the association between family history of 79 comorbidities and RA.

This case-control study identified 821 cases of RA in the Mayo Clinic Biobank (positive predictive value 95%) and matched three controls to each case based on age, sex, recruitment year, and location. Family history and adjustors were self-reported. Logistic regression estimated odds ratios (OR) and confidence intervals (CI) for RA risk by presence of family history for each comorbidity, adjusted for body mass index, race, and smoking.

Family history of several conditions were associated with developing RA, including rheumatologic autoimmune diseases (adjusted OR [aOR] 1.89, 95% CI 1.41,2.52), pulmonary fibrosis (aOR 2.12, 95% CI 1.16,3.80), inflammatory bowel disease (aOR 1.45, 95% CI 1.05,1.98), hyper/hypothyroidism (aOR 1.34, 95% CI 1.10,1.63), and obstructive sleep apnea (aOR 1.28, 95% CI 1.05,1.55). Parkinson's disease and type 2 diabetes were associated with a statistically decreased risk of RA that did not reach the pre-specified significance threshold of p<0.01 (aOR 0.70, 95% CI 0.49,0.98; aOR 0.81, 95% CI 0.67,0.97). Analyses among 143 cases of incident RA were similar and also suggested an association with family history of autism (OR 10.5, 95% CI 2.51,71.3).

Family history of several autoimmune and non-autoimmune comorbidities were associated with increased risk of RA, providing opportunity to identify novel populations at risk for RA.

Outcome Measures in Large-Vessel Vasculitis: Relationship Between Patient, Physician, Imaging, and Laboratory-Based Assessments.

Arthritis Care Res

To assess the relationship between measures of disease assessment in patients with large-vessel vasculitis.

Patients with giant cell arteritis (GCA) or Takayasu's arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: (a) patient-reported outcomes (PROs) [multi-dimensional fatigue inventory (MFI); patient global assessment (PtGlobal); 36-item short form health survey (SF-36); brief-illness perception questionnaire (BIPQ)], (b) physician-reported outcomes [physician global assessment (PhGlobal)], (c) Laboratory outcomes [CRP, ESR], and (d) imaging outcomes [PETVAS, a qualitative score of vascular FDG-PET activity].

Analyses were performed on 112 patients (GCA=56, TAK=56), over 296 visits, with median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGlobal was centrally linked to all other outcome types, but correlations were modest (ρ=0.12-0.32, p< 0.05). PETVAS, CRP, and PtGlobal were independently associated with clinically active disease. All four PROs strongly correlated with each other (ρ=0.35-0.60, p< 0.0001). PROs were not correlated with PETVAS and only PtGlobal correlated with CRP (ρ=0.16, p< 0.01). Patients whose clinical assessment changed from active disease to remission (n=29) had corresponding significant decrease in ESR, CRP, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n=11) had corresponding significant increase in CRP and PtGlobal at the active visit.

Measures of disease assessment in large-vessel vasculitis consist of independent, yet complementary outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes.

Effects of repetitive transcranial magnetic stimulation and multicomponent therapy in patients with fibromyalgia: a randomized controlled trial.

Arthritis Care Res

Fibromyalgia (FM) is a chronic painful condition partly due to alterations in pain modulation by the central nervous system. Multicomponent therapy (MT) and repetitive transcranial magnetic stimulation (rTMS) had both been reported as pain modulators in FM patients. The aim of this study was to compare the effects of rTMS on pain with a combination of MT and rTMS versus MT.

Thirty-nine FM patients with pain visual analogue scale (pVAS) ≥ 40mm were randomized to active or sham rTMS (high frequency, primary motor cortex M1) plus 12 weeks of MT (3 sessions per week combining aerobic training, pool based exercises and relaxation). rTMS was started 2 weeks prior MT and maintained until the end of the program (week 14). Assessments were achieved at baseline, at week 14, and 6 months (week 40) after completing the program. The main outcome was the pain reduction, assessed by the weekly mean daily self-reported level of pain. Secondary outcomes were cardiorespiratory fitness (graded maximal exercise test), cardiac autonomic adaptations and fibromyalgia impact (fibromyalgia impact, depression, sleep efficiency and pain catastrophizing scales).

The reduction of the weekly mean daily pain did not differ significantly between groups (repeated measures of ANOVA). Two-way ANOVAs showed that pVAS, as well as cardiorespiratory fitness, quality of life, depression and catastrophizing, improved significantly at week 14 and remained stable until week 40. Neither Cardiac autonomic adaptations nor sleep efficiency changed significantly.

rTMS did not reduce pain in FM patients who followed the MT program.

Using Cumulative Load to Explain How Body Mass Index and Daily Walking Relate to Worsening Knee Cartilage Damage Over Two Years: The MOST Study.

Arthritis Rheumatol

Knee cartilage damage is often linked to mechanical overloading. However, cartilage requires mechanical load to remain healthy, suggesting that underloading may be detrimental. We examined knee overloading and underloading by defining cumulative load as the joint effects of body mass index (BMI) and daily walking, and examined the relation of cumulative load to worsening cartilage damage over two years.

We used data from the Multicenter Osteoarthritis Study. BMI and steps/day via accelerometry were measured at the 60-month visit. Cartilage damage on magnetic resonance imaging (MRI) was semi-quantitatively scored using WORMS at the 60-month and 84-month visits; worsening damage was defined as increased WORMS between visits. Risk ratios and 95% confidence intervals (RR[95%CI]) were calculated using binomial regression, adjusting for potential confounders.

We included 964 participants (66.9 ± 7.5 years, 62% female, BMI: 29.7 ± 4.8 kg/m2 , 7153 ± 2591 steps/day). Participants with moderate (6000-7900) or high (>7900) steps/day and high BMI (>31 kg/m2 ) had 2.83[1.46-5.48] and 2.61[1.50-4.54] times the risk for worsening medial tibiofemoral damage, respectively, compared with those with similar steps/day and low BMI (18-27 kg/m2 ). Participants with low (<6000) steps/day and low BMI had 2.03[1.06-3.92] and 2.28[1.06-4.85] times the risk for worsening medial tibiofemoral and lateral patellofemoral damage, respectively, compared with those with high steps/day and low BMI. Effect estimates for other compartments did not reach statistical significance.

This study provides preliminary evidence that both overloading and underloading may be detrimental to medial tibiofemoral cartilage, and underloading may be detrimental for lateral patellofemoral cartilage.

Chondrocytes play a role in the development of rheumatoid arthritis via TMEM147-mediated NF-κB activation.

Arthritis Rheumatol

We previously reported that the co-activation of NF-κB and STAT3 in non-immune cells including synovial fibroblasts enhances the expression of NF-κB target genes, playing a role in chronic inflammation including rheumatoid arthritis (RA). Here we examined the role of NF-κB activation in chondrocytes to understand the pathogenesis of RA. Furthermore, we investigated TMEM147 as a representative NF-κB activator in chondrocytes.

Clinical samples from RA patients were analyzed by immunohistochemistry. Samples from polydactyly patients served as a control. The functional contribution of chondrocytes and TMEM147 to arthritis was examined in several mouse RA models. In vitro experiments including qPCR, RNA interference, immunoprecipitation and confocal microscopy were performed to investigate the mechanism of action of TMEM147 in chondrocytes.

Samples from RA patients and from the RA models showed co-activation of NF-κB and STAT3 in chondrocytes (p<0.001). This co-activation induced a synergistic expression of NF-κB targets in vitro (p<0.01). Chondrocyte-specific deletion of STAT3 significantly suppressed the development of cytokine-induced RA (p<0.01). TMEM147 was highly expressed in chondrocytes from RA patients and the RA models. Gene silencing of TMEM147 or anti-TMEM147 antibody treatment inhibited the cytokine-mediated activation of NF-κB in vitro (p<0.01) and suppressed the cytokine-induced RA in vivo (p<0.01). Mechanistically, TMEM147 molecules acted as a scaffold protein for a NF-κB complex that included breakpoint cluster region and casein kinase 2 to enhance NF-κB activity.

These results suggest that chondrocytes play a role in the development of RA via TMEM147-mediated NF-κB activation and provide a novel therapeutic strategy for RA.

Advancing rheumatoid arthritis synovial biopsy analysis: one B cell at a time.

Arthritis Rheumatol

While biologic therapies have dramatically improved the management of rheumatoid arthritis (RA), not all patients respond well to treatment and the...

B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure.

Arthritis Rheumatol

To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA).

Synovial biopsies, demographic and clinical data were collected from two RA cohorts (n=329): treatment-naïve early-RA (n=165) and TNF-inhibitor inadequate responders (TNFi-IR) established-RA (n=164). Synovial tissue underwent H&E and immunohistochemistry staining and semi-quantitative assessment for the degree of synovitis (0-9) and of CD20+ B cell infiltrate (0-4). B cell scores were validated by digital image analysis (DIA) and B cell lineage-specific transcript analysis (RNA-seq) in the early RA (n=91) and TNFi-IR (127) cohorts. Semi-quantitative CD20 scores were applied to classify patients as B cell rich (≥ 2) or poor (< 2).

Semi-quantitative B cell scores correlated with DIA quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of early-RA and 47.7% of TNFi-IR established-RA (p=0.025). B cell-rich patients showed higher levels of disease activity and sero-positivity for RF and ACPA in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts.

We describe a robust semi-quantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses. We demonstrate an ongoing B cell-rich synovitis in a larger proportion of patients with established RA that does not seem to be captured by standard clinimetric assessment.

Jaccoud Arthropathy.

Arthritis Rheumatol

A 55-year-old woman presented with a ten-year history of progressive deformities of her hands and feet. She had been diagnosed with systemic lupus ...

Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus.

Annals of the Rheumatic Diseases

Haematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both myeloid and lymphoid cell lineages. We reasoned that the aberrancies of immune cells in systemic lupus erythematosus (SLE) could be traced back to HSPCs.

A global gene expression map of bone marrow (BM)-derived HSPCs was completed by RNA sequencing followed by pathway and enrichment analysis. The cell cycle status and apoptosis status of HSPCs were assessed by flow cytometry, while DNA damage was assessed via immunofluorescence.

Transcriptomic analysis of Lin-Sca-1+c-Kit+ haematopoietic progenitors from diseased lupus mice demonstrated a strong myeloid signature with expanded frequencies of common myeloid progenitors (CMPs)-but not of common lymphoid progenitors-reminiscent of a 'trained immunity' signature. CMP profiling revealed an intense transcriptome reprogramming with suppression of granulocytic regulators indicative of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, and disturbed myelopoiesis. Despite the differentiation arrest, frequencies of BM neutrophils were markedly increased in diseased mice, suggesting an alternative granulopoiesis pathway. In patients with SLE with severe disease, haematopoietic progenitor cells (CD34+) demonstrated enhanced proliferation, cell differentiation and transcriptional activation of cytokines and chemokines that drive differentiation towards myelopoiesis, thus mirroring the murine data.

Aberrancies of immune cells in SLE can be traced back to the BM HSPCs. Priming of HSPCs and aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare.

4948/19-07-2016.