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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Antigen-driven selection of antibodies against SSA, SSB and the centromere 'complex', including a novel antigen, MIS12 complex, in human salivary glands.

Annals of the Rheumatic Diseases

Recent evidences have revealed that anti-SSA/SSB antibodies, the major autoantibodies in Sjögren's syndrome (SS), are produced in salivary glands. This study aims to clarify overall of autoantibody production at lesion site, including anti-centromere antibody (ACA)-positive SS.

Antibodies of antibody-secreting cells in human salivary glands were produced as recombinant antibodies. The reactivity of these antibodies and their revertants were investigated by ELISA and newly developed antigen-binding beads assay, which can detect conformational epitopes. The target of uncharacterised antibodies was identified by immunoprecipitation and mass spectrometry. Autoantibody-secreting cells in salivary gland tissue were identified by immunohistochemistry using green fluorescent protein-autoantigen fusion proteins.

A total of 256 lesion antibodies were generated, and 69 autoantibodies including 24 ACAs were identified among them. Beads assay could detect more autoantibodies than ELISA, suggesting autoantibodies target to antigens with native conformation. After somatic hypermutations were reverted, autoantibodies drastically decreased antigen reactivity. We showed that MIS12 complex, a novel target of ACA, and CENP-C are major targets of ACA produced in salivary glands by examining cloned antibodies and immunohistochemistry, whereas few anti-CENP-B antibodies were detected. The target profiling of serum ACA from 269 patients with SS, systemic sclerosis (SSc), primary biliary cirrhosis (PBC) and healthy controls revealed that ACA-positive patients have antibodies against various sites of centromere complex regardless of disease.

We showed direct evidences of antigen-driven maturation of anti-SSA/SSB antibody and ACA in SS lesion. ACA recognises centromere 'complex' rather than individual protein, and this feature is common among patients with SS, SSc and PBC.

Rheumatoid arthritis morning stiffness is associated with synovial fibrin and neutrophils.

Arthritis Rheumatol

Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. We sought to determine whether any histologic features of synovium associate with this symptom.

Patient reports of morning stiffness duration, stiffness severity and disease activity scores (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Histopathology of synovium was scored for 10 features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells detritus, neutrophils and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays.

Stiffness severity and morning stiffness duration were both significantly associated with DAS28 (p=0.0001 and p=0.001 respectively). None of the synovial features examined were associated with patient-reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly (P<0.0001) associated with patient report of greater than one hour of morning stiffness, such that 73% of patients with both synovial fibrin and neutrophils report more than one hour of morning stiffness. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells (p=0.008). DNase1 treatment of necrotic neutrophils abrogated the delay in fibrinolysis.

In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiological phenomena.

Disease severity is linked to an increase in autoantibody diversity in IgG4-related disease.

Arthritis Rheumatol

Four autoantigens have been described recently in IgG4-related disease (IgG4-RD): prohibitin, annexin A11, laminin 511-E8, and galectin-3. However, no external validation has been performed and the possibility that some individuals break tolerance to more than one autoantigen has not been explored.

Autoantibody responses against prohibitin, annexin A11 and laminin 511-E8 were measured by ELISA among a clinically diverse cohort of IgG4-RD patients (n=100). Autoantibody responses were correlated with disease severity and organ distribution.

The frequencies of IgG4 autoantibody responses against prohibitin (10%), annexin A11 (12%), and laminin 511-E8 (7%) were not significantly different from those of controls. A portion of the cohort (n = 86) had been analyzed previously at our center for anti-galectin-3 antibody responses with 25 (29%) having IgG4 anti-galectin-3 antibodies. Among these 86 subjects, 32 (37%) had IgG4 antibodies to at least one of the 4 auto-antigens and 12 (14%) showed reactivity to ≥2 of the tested antigens. The subset of patients with ≥2 autoantibodies had higher total IgG1, IgG2, IgG4, and C-reactive protein levels; were more commonly hypocomplementemic; and were more likely to have visceral organ involvement.

Antibodies against prohibitin, annexin A11, and laminin 511-E8 were found in only a small portion of patients with IgG4-RD. A subset of IgG4-RD patients, however, had IgG4 antibodies against ≥2 autoantigens. Patients with antibodies against ≥2 autoantigens present with robust IgG subclass elevations, complement consumption, and visceral organ involvement. This broader break in immunological tolerance in IgG4-RD was associated with more severe disease.

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Preexisting Autoimmune Disease: A Nationwide Multicenter Cohort Study.

Arthritis Rheumatol

We read with great interest the article by Tison et al profiling safety and efficacy of immune checkpoint inhibitors (ICIs) in individuals with can...

Decomposition Analysis of Spending and Price Trends for Biologic Anti-Rheumatic Drugs in Medicare and Medicaid.

Arthritis Rheumatol

Billions of public dollars are spent each year on biologic disease-modifying anti-rheumatic drugs (bDMARDs), but the drivers of recent increases in bDMARD spending are unclear. We characterized changes in total spending and unit-prices for bDMARDs in Medicare and Medicaid and quantified the major sources of these spending increases.

We accessed drug spending data for years 2012-2016, covering all Medicare Part B (fee-for-service), Part D, and Medicaid enrollees. After calculating five-year changes in total spending and unit-prices for each bDMARD and in-aggregate, we performed standard decomposition analyses to isolate four sources of spending growth: drug prices, uptake [# recipients], treatment intensity [mean # doses/claim], and treatment duration [annual # claims/recipient]), both excluding and including time-varying rebates.

From 2012-2016, annual spending on public-payer claims for the 10 included bDMARDs more than doubled ($3.8 to $8.6 billion), with median drug price increases of 51% in Part D (mean 54%) and 8% within Part B (mean 21%). Adjusting for general inflation, unit-price increases alone accounted for 57% of the five-year, $3.0 billion spending increase within Part D; 37% was from increased uptake. Accounting for time-varying rebates, prices were still responsible for 54% of increased spending. Unit-prices and spending were lower under Medicaid than Part D, but temporal trends and contributors were similar.

Post-market drug-price changes alone account for the majority of recent spending growth for bDMARDs. Policy interventions targeting price increases, particularly under Part D plans, may help mitigate drug financial burdens for public payers and bDMARD recipients.

Cancer immunotherapy in patients with preexisting autoimmune diseases.

Arthritis Rheumatol

We read with great interest the letter of Xie et al commenting on our article "Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with...

TNFR2 associates with FoxP3 stability and identifies asubset of regulatory T cells that are specifically expanded by anti-TNF treatments in rheumatoid arthritis.

Arthritis Rheumatol

To study the involvement of regulatory T cells (Tregs) expressing tumor necrosis factor-αreceptor 2 (TNFR2) incontrol of experimental inflammation and response to treatment in rheumatoid arthritis (RA) and spondyloarthritis (SpA).

The role of TNFR2 inTregswas exploredusing amultilevel translational approach.Tregstability was evaluatedby analyzing methylation status of the foxp3locus by bisulfite sequencing. Two models of inflammation (imiquimod-induced skin inflammationand delayed type hypersensitivity arthritis, DTHA) were induced inTNFR2-deficient (TNFR2-/- ) micewith or without transfer of purified CD4+ CD25+ cellsfrom wild-type (wt) mice.The evolution of the TNFR2+ Tregpopulation before and after targetedtreatment was monitored in individuals with RA andSpA.

Foxp3gene methylation was greaterin Tregs from TNFR2-/- (50%) thanwt(36,7%)mice. In cultured Tregs, TNF-α enhanced Foxp3 expression maintenance and proliferation through TNFR2 signaling. Imiquimod-induced skin inflammation and DTHA were aggravated in TNFR2-/- mice as compared to wt mice (p<0.05 for skin inflammation and p<0.0001 for ankle swelling during DTHA).Adoptive transfer of wtTregs into TNFR2-/- mice prevented from arthritis aggravation. TNFR2+ Tregfrequency was increased (p<0.01)at 3 months (65.2 ± 3.1) of anti-TNF-α treatments vs. the baseline(49.1 ± 5.5) in RA individuals, but not in those receiving tocilizumab. In contrast, in anti-TNF-αtreated SpAindividuals, TNFR2+ Tregfrequency was not modified.

TNFR2 expression identifies a subset of Tregscharacterized by stable expression of Foxp3 via genehypomethylation, whose adoptive transfer ameliorates experimental inflammation. Expansion and activation of these TNFR2+ Tregs may be one of the mechanisms by which anti-TNF-α agents control inflammation in RA but not SpA.

Histopathology of catastrophic antiphospholipid syndrome-associated nephropathy in a SLE patient without concurrent lupus nephritis.

Arthritis Rheumatol

A 35-year-old African American male with a history of seizures, presented with nausea, vomiting, abdominal pain, thrombocytopenia (platelet count o...

Rheumatoid Arthritis Flares after Total Hip and Total Knee Arthroplasty: Outcomes at 1 year.

Arthritis Care Res

Most RA patients undergoing total hip(THA) and total knee arthroplasty(TKA) have active RA and report post-operative flares; whether RA disease activity or flares increase risk of worse pain and function scores 1 year later is unknown.

RA patients were enrolled before THA/TKA. Patient Reported Outcomes (PROS) including Hip and Knee Osteoarthritis/disability and injury Outcome Scores (HOOS/KOOS) and MD assessments of disease characteristics and activity (DAS 28, CDAI) were collected before surgery. PROS were repeated at 1 year. Post-operative flares were identified using RA Flare Questionnaire weekly for 6 weeks, and defined by concordance between patient report plus MD assessment. We compared baseline characteristics and HOOS/KOOS scores using two-sample t-test/Wilcoxon rank-sum and Chi-squared/Fisher's exact tests. We used multivariate linear and logistic regression to determine association of baseline characteristics, disease activity, and flares, with 1-year outcomes.

One-year HOOS/KOOS scores were available for 122 patients (56THA/66TKA). Although HOOS/KOOS pain was worse for patients who flared within six weeks of surgery; absolute improvement was not different. In multivariable models, baseline DAS28 predicted 1-year HOOS/KOOS pain and function; each 1 unit increase in DAS28 worsened 1-year pain by 2.41 (SE=1.05, p=.02) and 1-year function by 4.96 (SE=1.17, p=.0001). Post-operativeerative flares were not independent risk factors for pain or function scores.

Higher disease activity increased risk of worse pain and function one year after arthroplasty, post-operative flares did not.

Determinants of Patient-Reported Psoriatic Arthritis Impact of Disease: An Analysis of the Association with Gender in 458 Patients from 14 Countries.

Arthritis Care Res

Gender differences may modify symptoms, disease expression, and treatment effects. The objective was to evaluate the link between life impact and gender in psoriatic arthritis (PsA).

ReFlaP (NCT03119805) was a study in 14 countries of consecutive adult patients with definite PsA. Participants underwent comprehensive PsA assessment: Disease Activity in PSoriatic Arthritis (DAPSA), Minimal Disease Activity (MDA), and Psoriatic Arthritis Impact of Disease (PsAID). Disease activity was compared by gender using t-tests or Wilcoxon tests. The association of PsAID with gender was analyzed using hierarchical generalized linear models.

Of 458 participants 50.2% were male, mean age (SD) 53.1 (12.6) years, PsA duration 11 (8.2) years, and 51.5% taking bDMARDs. Women versus men had worse Leeds enthesitis index: 0.8 (1.7) / 0.3 (0.9), pain [numerical rating scale 0-10 (NRS)]: 4.7 (2.7) / 3.5 (2.7), HAQ-DI: 0.9 (0.7) / 0.5 (0.6), fatigue NRS: 5.2 (3) / 3.3 (2.8), PsAID: 4.1 (2.4) / 2.8 (2.3), p<0.001 for all, and were less frequently at treatment target (T2T): DAPSA (DAPSA cut-offs ≤4 remission, >4 and ≤14 low disease activity): 16.9 (14.9) / 12.6 (16.6), MDA: 25.7% / 50.0%, p<0.001 for all. High life impact (PsAID≥4) was associated with female gender [odds ratio (OR) 2.3], enthesitis (OR 1.34), tender joints (OR 1.10) p<0.001 for all, and comorbidities (OR 1.22, p=0.002).

High life impact was independently associated with female gender, enthesitis, comorbidities, and tender joints. At T2T, women vs men had higher life impact. Life impact needs to become part of PsA T2T strategies.

Economic evaluation of damage accrual in an international SLE inception cohort using a multi-state model approach.

Arthritis Care Res

There is a paucity of data regarding healthcare costs associated with damage accrual in systemic lupus erythematosus (SLE). We describe costs associated with damage states across the disease course using multi-state modeling.

Patients from 33 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology (ACR) Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multi-state model.

1687 patients participated, 88.7% female, 49.0% of Caucasian race/ethnicity, mean age at diagnosis 34.6 years (SD 13.3), and mean follow up 8.9 years (range 0.6-18.5). Annual costs were higher in those with higher SDIs (SDI ≥ 5: $22 006 2019 CDN, 95% CI $16 662, $27 350 versus SDI=0: $1833, 95% CI $1134, $2532). Similarly, 10-year cumulative costs were higher in those with higher SDIs at the beginning of the 10-year interval (SDI ≥ 5: $189 073, 95% CI $142 318, $235 827 versus SDI=0: $21 713, 95% CI $13 639, $29 788).

Patients with the highest SDIs incur 10-year cumulative costs that are almost 9-fold higher than those with the lowest SDIs. By estimating the damage trajectory and incorporating annual costs, damage can be used to estimate future costs, critical knowledge for evaluating the cost-effectiveness of novel therapies.

Fibrofog in daily life: An examination of ambulatory subjective and objective cognitive function in fibromyalgia.

Arthritis Care Res

Perceived cognitive dysfunction in fibromyalgia (FM), "fibrofog," is common. Prior laboratory-based studies have limited our understanding of cognitive function in FM in daily life. The aim of this study is to explore levels of subjective and objective cognitive functioning and the association between subjective and objective aspects of cognition in persons with and without FM in the lived environment.

Participants (n=50 adults with FM; n= 50 adults without FM matched on age, sex, and education) completed baseline measures of subjective and objective (NIH Toolbox) cognitive functioning. Then, they completed ecological momentary assessments of cognitive clarity and speed and tests of processing speed and working memory, via a smart phone app, 5X/day for 8 days.

On baseline objective measures, the FM group demonstrated poorer cognitive functioning across three NIH Toolbox tests. There were no strong correlations between subjective and objective cognitive functioning in both the FM and control group. In the lived environment, the FM group demonstrated poorer subjective cognition and objective working memory; groups did not differ on processing speed. Momentary ratings of subjective cognitive dysfunction were significantly related to changes in objective processing speed but not working memory, with no group differences.

Findings indicate worse lab-based and ambulatory subjective and objective cognitive function for those with FM compared to those without FM. Similar associations between measures of subjective and objective cognitive functioning for the groups suggest that people with FM are not overstating cognitive difficulties. Future research examining contributors to ambulatory fibrofog is warranted.