Onset Of Arthritis Research Articles

Card9/neutrophil signalling axis promotes IL-17A-mediated ankylosing spondylitis

ObjectivePolymorphisms in the antifungal signalling molecule CARD9 are associated with ankylosing spondylitis (AS). Here, we investigated the cellular mechanism by which CARD9 controls pathogenic Th17 responses and the onset of...

Factors Associated With Diagnostic Delay in Axial Spondyloarthritis: Impact of Clinical Factors and Social Vulnerability.

Patients with axial spondyloarthritis (axSpA) often experience significant delay between symptom onset and diagnosis for reasons that are incompletely understood. We investigated associations between demographic, medical, and socioeconomic factors and axSpA diagnostic delay. We identified patients meeting modified New York criteria for ankylosing spondylitis (AS) or 2009 Assessment of Spondyloarthritis International Society criteria for axSpA in the Mass General Brigham health care system between December 1990 and October 2021. We determined the duration of diagnostic delay, defined as the duration of back pain symptoms reported at diagnosis, as well as disease manifestations and specialty care prior to diagnosis from the electronic health record. We obtained each patient's Social Vulnerability Index (SVI) by mapping their address to the US Centers for Disease Control SVI Atlas. We examined associations among disease manifestations, SVI, and diagnostic delay using ordinal logistic regression. Among 554 patients with axSpA who had a median diagnostic delay of 3.8 years (interquartile range 1.1-10), peripheral arthritis (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.93) and older age at symptom onset (OR 0.83, 95% CI 0.78-0.88 per five years) were associated with shorter delay. AS at diagnosis (OR 1.85, 95% CI 1.30-2.63), a history of uveitis prior to diagnosis (OR 2.77, 95% CI 1.73-4.52), and higher social vulnerability (defined as national SVI 80th to 99th percentiles; OR 1.99, 95% CI 1.06-3.84) were associated with longer diagnostic delay. Older age at back pain onset and peripheral arthritis were associated with shorter delay, whereas uveitis was associated with longer diagnostic delay. Patients with higher socioeconomic vulnerability had longer diagnostic delay independent of clinical factors.

Relationship of weight change patterns from young to middle adulthood with incident rheumatoid arthritis and osteoarthritis: a retrospective cohort study.

The relationship between weight change patterns and arthritis onset, specifically rheumatoid arthritis (RA) and osteoarthritis (OA), is unclear. We examined the association between weight changes from young adulthood to midlife and arthritis onset. Using data from NHANES 1999-2018, participants with self-reported arthritis were selected. Age at diagnosis determined arthritis onset. Weight change patterns were based on BMI at age 25 and 10 years before the survey. Patterns were categorized as stable non-obese, non-obese to obese, obese to non-obese, and stable obese. Cox regression models and restricted cubic spline (RCS) analysis were employed, calculating hazard ratios (HRs) and 95% confidence intervals (CIs) considering covariates. Out of 20,859 participants (male 11,017, 52.82%), 4922 developed arthritis over a mean 8.66-year follow-up. Compared to stable non-obese individuals, the HRs for arthritis were 1.55 (95% CI=1.45 to 1.66, P < 0.0001) for non-obese to obese and 1.74 (95% CI=1.56 to 1.95, P < 0.0001) for stable obese. Those gaining 10-20kg had a HR of 1.33 (95% CI=1.22 to 1.46, P < 0.0001), and gains >20kg had a HR of 1.56 (95% CI=1.42 to 1.71, P < 0.0001), compared to stable weight (change within 2.5kg). Identical results observed for OA and RA. RCS showed a nonlinear relationship between weight change and arthritis (all P < 0.01). Stable obesity and weight gain during adulthood increase arthritis risk. Maintaining a non-obese weight throughout adult years might reduce arthritis risk in later life.

The gut homeostasis-immune system axis: novel insights into rheumatoid arthritis pathogenesis and treatment.

Rheumatoid arthritis is a widely prevalent autoimmune bone disease that imposes a significant burden on global healthcare systems due to its increasing incidence. In recent years, attention has focused on the interaction between gut homeostasis and the immune system, particularly in relation to bone health. Dysbiosis, which refers to an imbalance in the composition and function of the gut microbiota, has been shown to drive immune dysregulation through mechanisms such as the release of pro-inflammatory metabolites, increased gut permeability, and impaired regulatory T cell function. These factors collectively contribute to immune system imbalance, promoting the onset and progression of Rheumatoid arthritis. Dysbiosis induces both local and systemic inflammatory responses, activating key pro-inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-6, and Interleukin-17, which exacerbate joint inflammation and damage. Investigating the complex interactions between gut homeostasis and immune regulation in the context of Rheumatoid arthritis pathogenesis holds promise for identifying new therapeutic targets, revealing novel mechanisms of disease progression, and offering innovative strategies for clinical treatment.

Evaluation of Autoreactive Responses.

Loss of tolerance to self-antigens is considered to be one of the initial reasons for the onset of rheumatoid arthritis (RA). Identification of self-antigens and evaluation of autoreactive antibodies can foster understanding of the pathogenesis of the disease and the development of new therapeutics. By detection of responses to a particular self-antigen, such as α-enolase, keratin, fibrinogen, fibronectin, collagen, or vimentin, in patient- and animal model-derived samples, high-affinity T-cell receptor-dependent activation of autoreactive T cells to self-antigens can be elucidated. This chapter introduces a simple method to estimate T-cell-autoreactive responses to type II collagen (CII) in a murine collagen-induced arthritis model. A limiting dilution system is established in order to assess CII-dependent T-cell responses, which are reflected by the level of cytokine release.

Association of Human Papillomavirus Vaccination with Risk for Rheumatoid Arthritis

Introduction: The potential association between Human papillomavirus (HPV) vaccination and the onset of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) remains a pivotal point of exploration in immunization safety discourse. Method: This retrospective cohort study aims to ascertain the risk of RA and JIA following HPV vaccination, utilizing the TriNetX database, tracking the health trajectories of 32,165,650 females, from January 1, 2013, to December 31, 2022. By applying inclusion and exclusion criteria, we formed a balanced cohort of 344,165 HPV-vaccinated individuals, the propensity score-matched 1:1 with unvaccinated controls based on a range of demographic and clinical parameters. This study used the Cox proportional hazards model to analyze the risk of RA and JIA after HPV vaccination, expressed the results by adjusted hazard ratio (aHR) and 95% confidence interval (CI), and used Kaplan-Meier survival analysis. Results: The analysis showed that over a follow-up period of up to 10 years after vaccination, the risks of RA and JIA were significantly reduced in the HPV vaccination group, with aHR of 0.428 (95% CI: 0.372-0.492) and 0.310 (95% CI: 0.262-0.367) respectively. This trend persisted in a sensitivity analysis that replaced the control group with influenza-vaccinated individuals. Subgroup analyses showed that the risk of RA and JIA was significantly reduced in the 9-18 and 19-26 age groups, across ethnic backgrounds, and in the obesity and asthma subgroups, but still among those with a smoking history, the risk reduction was not statistically significant. Conclusion: Our findings highlight the significant protective effect of the HPV vaccine against RA and JIA. Further research is needed to delve deeper into this molecular mechanism.

Течение ревматоидного артрита у пациентки с дебютом заболевания в старческом возрасте

A description of the clinical case of a female patient with the onset of rheumatoid arthritis (RA) in an old age is presented. The disease began acutely against the background of comorbid pathology and was manifested by high activity, multiple involvement of large and small joints, and their swelling. A thorough examination was performed to exclude paraneoplastic syndrome. Comorbid conditions and impaired renal function did not allow the prescription of basic drugs; a good effect was obtained from methylprednisolone. Management of elderly and senile patients with RA requires an individual approach, taking into account concomitant diseases and drug tolerability.

A rare case of early onset arthritis as a sequelae of fracture dislocation of ankle

A rare case of early onset arthritis as a sequelae of fracture dislocation of ankle

Role of macrophages in the onset, maintenance, or control of arthritis caused by alphaviruses.

Arthritogenic alphaviruses are mosquito-borne viruses that cause a debilitating rheumatic disease characterized by fever, headache, rash, myalgia, and polyarthralgia with the potential to evolve into a severe and very prolonged illness. Although these viruses have been geographically restricted by vector hosts and reservoirs, recent epidemics have revealed the risks of their spread worldwide. In this review, we aim to discuss the protective and pathological roles of macrophages during the development of arthritis caused by alphaviruses. The progression to the chronic phase of the disease is related to the extension of viral replication and the maintenance of articular inflammation, in which the cellular infiltrate is predominantly composed of macrophages. We explore the possible implications of macrophage polarization to M1/M2 activation phenotypes, drawing a parallel between alphavirus arthritis and rheumatoid arthritis (RA), a chronic inflammatory disease that also affects articular tissues. In RA, it is well established that M1 macrophages contribute to tissue damage and inflammation, while M2 macrophages have a role in cartilage repair, so modulating the M1/M2 macrophage ratio is being considered as a strategy in the treatment of this disease. In the case of alphavirus-induced arthritis, the picture is more complex, as proinflammatory factors derived from M1 macrophages contribute to the antiviral response but cause tissue damage, while M2 macrophages may contribute to tissue repair but impair viral clearance.

Dupilumab-associated inflammatory arthritis: a literature review.

Dupilumab is a fully human monoclonal antibody that acts by inhibiting the interleukin (IL)-4 receptor subunit α, and hence the IL-4 and IL-13 signalling pathway. Dupilumab treatment has been linked to the onset of T helper 17-driven inflammatory diseases, including cases of seronegative arthritis and enthesitis. To date, dupilumab-associated inflammatory arthritis (DAIA) represents a relatively unknown adverse event, initially reported in single cases or case series reports. Indeed, the onset of DAIA may not be promptly recognized, and is probably underestimated. Here we have reviewed the available English literature regarding arthritis and enthesitis onset during dupilumab treatment for atopic dermatitis, aiming to improve rapid recognition and thus prompt treatment of these diseases.

Elderly-Onset Rheumatoid Arthritis: Characteristics and Treatment Options.

Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.

Increased expression of omentin-1 is associated with synovitis and bone destruction in rheumatoid arthritis.

The aberrant expression of omentin-1 had been reported in type 2 diabetes and cardiovascular disease. Here, we investigated the expression and role of omentin-1 in rheumatoid arthritis (RA). The expression of omentin-1 in RA and in the normal population was detected by ELISA and immunohistochemistry, and collagen-induced arthritis (CIA) mice were used to detect the role of omentin-1 in RA. We found that the expression of omentin-1 was elevated in serum of RA patients compared with healthy controls (p=0.004), and in the RA disease activity group compared with the disease remission group (p<0.001). In addition, the level of omentin-1 in RA patients was positively correlated with CRP (r=0.427, p=0.002), ESR (r=0.454, p<0.001) and DAS28 (r=0.496, p<0.001; r=0.661, p<0.001, respectively). Multivariable analysis showed that omentin-1 alone was associated with disease activity state (OR=1.018, p=0.004). Immunohistochemical results showed that omentin-1 was increased in the synovium of RA and CIA mice. Omentin-1 injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia and bone erosion in CIA mice. Moreover, omentin-1 treatment markedly enhanced IL-6, TNF-α, MMP-3, MMP-13 and RANKL in the joint tissue of CIA mice. Our results suggested that omentin-1 was up-regulated in RA and can exacerbate synovitis and joint destruction which may provide new insight into the pathogenesis of RA.

Factors Influencing Major Life-Changing Decisions in Patients with Psoriasis: A Cross-sectional Study.

Psoriasis is a chronic inflammatory disease associated with significant impairment in quality of life. Although quality of life in patients with psoriasis has been widely studied, there is little evidence regarding the impact of psoriasis on major life-changing decisions (MLCD). The aims of this study are to describe the impact of psoriasis on MLCD and to explore the potential clinical factors associated with MLCD. This cross-sectional study included 113 patients with psoriasis, regardless of disease severity, duration, or current treatment. The impact of the disease on different MLCD, including those related to professional career, decision of having children, choice of clothing, and leisure activities, was explored using Likert scales. Mean age was 51 years old and female to male ratio was 1.08 (54/50). The mean Psoriasis Area Severity Index was 3.75, and 30% (35/113) of the patients had psoriatic arthropathy. The most affected MLCD were career choice (median (interquartile range) score 3 (2-4)), social relationships (2 (1-3)), choice of clothing (2 (1-3)), job performance, absenteeism, and choice of holiday destination (1 (0-2)). Female sex, early age of onset and psoriatic arthropathy were associated with a greater impact of the disease on MLCD (p < 0.05). The results showed that a range of MLCD are affected in patients with psoriasis, such as career choice, job performance, absenteeism, or choice of clothing. Female sex, psoriatic arthritis and early age of onset are factors associated with a greater impact on MLCD. In order to limit the long-term negative effects of psoriasis on patients, special attention should be paid to detection of psoriatic arthritis, and to patients with early disease onset.

Early to Mid-Term Follow-up of Total Ankle Arthroplasty in Patients &lt;35 Years

Category: Ankle Arthritis; Ankle Introduction/Purpose: Younger age remains at the forefront of discussion when deciding between total ankle arthroplasty (TAA) and the ankle arthrodesis (AA) for treatment of end stage ankle arthritis. Unlike in the hip and knee, ankle arthritis is typically post-traumatic and presents at a much younger patient age. With the goal of preserving ankle motion, improving function and limiting adjacent joint degeneration, TAA has been shown to be safe and effective in patients &lt; 55 years of age. However, it is not uncommon for debilitating ankle arthritis to occur in individuals within their fourth or even third decade of life resulting in significant patient comorbidity. The purpose of our study was to evaluate patient reported outcome measures and survivorship after primary TAA in patients &lt; 35 years old. Methods: A retrospective chart review was conducted of patients &lt; 35 years old who underwent primary TAA at a single institution from 2007-2020. Patient demographics, outcome measures, and complications were recorded. All patients had a minimum clinical follow up of 2 years. Patient reported outcome measures collected included VAS, SMFA dysfunction index, SF-36 and AOFAS hindfoot scores. Outcome measures were evaluated preoperative, 1 year postoperative, and at final follow up. Paired t-tests were performed to compare individual patients’ changes in PRO from preoperative to postoperative timepoints. Implant survivorship was evaluated as well as complications related to the index procedure. Implant survivorship based on need for complete revision of either the tibial or talar component Results: Twelve patients were included in the study. Average age at surgery was 28.5 years. Mean follow-up was 7.2 years. Mean VAS improved from 53.8 preoperatively to 14.7 (p= 0.152) at 1-year and 12.5 (p= 0.045) at final follow up, respectively. Mean SMFA improved from 40.0 preoperatively to 27.1 (p= 0.018) at 1-year and 24.0 (p= 0.006) at final follow up, respectively. SF-36 and AOFAS hindfoot scores also improved at 1 year and final follow-up compared to preoperative values [SF-36: 45.3 to 60.2 (p=0.06) and 67.0 (p=0.016); AOFAS: 40.6 to 70 (p= 0.08) and 68.9 (p=0.068)]. One patient required talar component revision due to aseptic loosening. One patient required subsequent removal of heterotopic bone due to impingement. No patients developed infection requiring surgical intervention. Conclusion: The onset of ankle arthritis typically occurs at a much younger age compared with that of the hip and knee and has a detrimental impact on patient quality of life. Despite a young age and increased activity demands, our results demonstrated that patients &lt; 35 with end-stage ankle arthritis undergoing TAA demonstrated improved patient-reported outcomes greater than 2 years after surgery. Survivorship of TAA in our study was 91.7% at a mean follow-up of 7.2 years. We believe that TAA is a safe, effective and durable option for very young patients with high patient satisfaction at early to mid-term follow up.

A-085 Analytical Performance of BÜHLMANN sCAL® turbo, a New, Reliable and Precise High-Throughput Assay to Assess the Inflammatory Status of Patients

Abstract Background Serum calprotectin plays an important pro-inflammatory role in the innate immune system and is a promising marker with several potential applications in rheumatoid arthritis, juvenile idiopathic arthritis and systemic onset juvenile idiopathic arthritis. Serum calprotectin can be a useful tool to monitor disease activity and predict treatment response in these patients. Methods The aim of this work was to evaluate the analytical performance of BÜHLMANN sCAL® turbo, a new turbidimetric test on clinical chemistry analyzers for the determination of calprotectin levels in serum. Assay characteristics were established according to CLSI guidelines (CLSI C28-A3, EP05-A3, EP07-A3, and EP09-A3). 111 samples were measured using 3 lots over 3 days and compared to another commercially available assay. Results The analytical measuring range from 0.23 to 15 µg/mL, extended to 225 µg/mL with an additional dilution in an automated rerun on a clinical chemistry analyzer, is suitable to address the described pathologies. 160 self-declared healthy adults (m/w) aged 18–83 years exhibit reference limits of 1.77 and 1.10 µg/mL when sampled either in a native tube or a gel separator tube and processed within 3.4 h after collection, respectively. With a within-laboratory precision up to 5.1% and a reproducibility up to 11.1% the method is precise, reliable and suitable for routine use. Tested concentrations of oral and injectable pharmaceuticals showed no interference. Hemolyzed samples are not recommended. It shows good comparison to an existing commercial assay with a bias of 12.5% (Bland-Altman) and a slope of 1.16 (Passing-Bablok). Conclusion A high-throughput test on clinical chemistry analyzers is now available with the turbidimetric BÜHLMANN sCAL® turbo allowing reliable and precise measurements of serum calprotectin levels.

Circ_0000396 suppresses the proliferation and inflammation of rheumatoid arthritis synovial fibroblasts by targeting miR-574-5p/RSPO1 axis

BackgroundCircular RNAs (circRNAs) are important regulators on the onset and progression of rheumatoid arthritis (RA). Our purpose is to explore the role and underpin mechanism of circ_0000396 in RA progression.MethodsRA patients (n = 39) and healthy volunteers (n = 33) were recruited from the Affiliated Hospital of Shaanxi University of Chinese Medicine for the present work. Circ_0000396, microRNA-574-5p (miR-574-5p) and R-spondin 1 (RSPO1) RNA levels were analyzed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and 5-ethynyl-2′-deoxyuridine (EDU) assay. Cell apoptosis was assessed by flow cytometry. Protein expression levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, Cyclin E1, BCL2-associated × protein (Bax), B-cell lymphoma-2 (Bcl2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and RSPO1 were detected by western blot assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the secretion of pro-inflammatory cytokines including IL-1β and TNF-α. The interaction between miR-574-5p and circ_0000396 or RSPO1 was confirmed by dual-luciferase reporter assay and RNA-pull down assay.ResultsCirc_0000396 expression was notably down-regulated in RA patients compared with healthy controls. Circ_0000396 overexpression suppressed the proliferation and inflammatory response and triggered the apoptosis of RA synovial fibroblasts (RASFs), accompanied by decreases in PCNA, Cyclin D1, Cyclin E1, Bcl2, IL-1β and TNF-α protein expression and an increase in Bax protein expression. Circ_0000396 acted as a molecular sponge for miR-574-5p, and circ_0000396 overexpression-mediated protective effects on RASFs dysfunction were largely reversed by the introduction of miR-574-5p mimics. miR-574-5p interacted with the 3’ untranslated region (3’UTR) of RSPO1, and miR-574-5p negatively regulated RSPO1 expression in RASFs. Circ_0000396 could up-regulate the expression of RSPO1 by sponging miR-574-5p in RASFs. RSPO1 interference largely overturned circ_0000396 overexpression-mediated effects in RASFs.ConclusionCirc_0000396 restrained the proliferation and inflammation and induced the apoptosis of RASFs by mediating miR-574-5p/RSPO1 axis, which provided novel potential targets for RA treatment.

Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss

BackgroundThe types of bone damage in rheumatoid arthritis (RA) include joint erosion, periarticular osteoporosis, and systemic osteoporosis. Janus kinase (JAK) inhibitors ameliorate inflammation and joint erosion in RA, but their effect on the three types of bone loss have not been reportedly explored in depth. We aimed to clarify how JAK inhibitors influence the various types of bone loss in arthritis by modulating osteoclastic bone resorption and/or osteoblastic bone formation.MethodsCollagen-induced arthritis (CIA) mice were treated with a JAK inhibitor after the onset of arthritis. Micro-computed tomography (μCT) and histological analyses (bone morphometric analyses) on the erosive calcaneocuboid joint, periarticular bone (distal femur or proximal tibia), and vertebrae were performed. The effect of four different JAK inhibitors on osteoclastogenesis under various conditions was examined in vitro.ResultsThe JAK inhibitor ameliorated joint erosion, periarticular osteopenia and systemic bone loss. It reduced the osteoclast number in all the three types of bone damage. The JAK inhibitor enhanced osteoblastic bone formation in the calcaneus distal to inflammatory synovium in the calcaneocuboid joints, periarticular region of the tibia and vertebrae, but not the inflamed calcaneocuboid joint. All the JAK inhibitors suppressed osteoclastogenesis in vitro to a similar extent in the presence of osteoblastic cells. Most of the JAK inhibitors abrogated the suppressive effect of Th1 cells on osteoclastogenesis by inhibiting IFN-γ signaling in osteoclast precursor cells, while a JAK inhibitor did not affect this effect due to less ability to inhibit IFN-γ signaling.ConclusionsThe JAK inhibitor suppressed joint erosion mainly by inhibiting osteoclastogenesis, while it ameliorated periarticular osteopenia and systemic bone loss by both inhibiting osteoclastogenesis and promoting osteoblastogenesis. These results indicate that the effect of JAK inhibitors on osteoclastogenesis and osteoblastogenesis depends on the bone damage type and the affected bone area. In vitro studies suggest that while JAK inhibitors inhibit osteoclastic bone resorption, their effects on osteoclastogenesis in inflammatory environments vary depending on the cytokine milieu, JAK selectivity and cytokine signaling specificity. The findings reported here should contribute to the strategic use of antirheumatic drugs against structural damages in RA.

Prevalence of early and late onset of chronic diseases and multimorbidity and its association with physical, mental and functional health among older Indian adults

BackgroundIdentifying people with early and late onset of chronic conditions might help target the subpopulations that are more vulnerable to negative mental, physical and functional health outcomes. The current study aimed to examine the association of early and late onset of chronic single and multiple morbidities with self-perceived physical and mental health, functional limitations and physical inactivity among older Indian adults.MethodsCross-sectional study was conducted using data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the present study was 31,386 older adults age 60 years or older. Multivariable binary logistic regression analysis was used to establish the association between the outcomes (poor perceived physical/mental health, functional difficulty and physical inactivity) and explanatory variables (early [ = < 50 years of age] and late [> 50 years]) onset of chronic illnesses such as hypertension, diabetes, heart attack, heart disease, stroke, cancer, lung disease, arthritis, osteoporosis and psychiatric disease).ResultsOverall, 24.21% of the sample population had poor self-perceived physical health, whereas 8.67% of participants had poor self-perceived mental health. The prevalence of difficulty in ADL, difficulty in IADL, and physical inactivity was 23.77%, 48.36%, and 68.9%, respectively. Odds of poor perceived mental health were higher for the respondents with early as well as late onset of hypertension, stroke, and arthritis; while individuals with late onset of diabetes, and heart disease had higher odds of poor perceived mental health than those without chronic disease. Individuals with early onset of single morbidity were more likely to report ADL difficulty (adjusted odds ratio [AOR]: 1.33, confidence interval [CI]: 1.06–1.67); while those with late onset of single (AOR: 1.34, CI: 1.17–1.53) and multimorbidity (AOR: 1.91, CI: 1.63–2.24) were more likely to report ADL difficulty compared with individuals without morbidity. Individuals with early as well as late-onset of multimorbidity had more than two times higher odds of reporting poor physical health, poor mental health and IADL difficulty compared with individuals without chronic disease.ConclusionsThe present study revealed that early and/or late onset of chronic single and/or multiple morbidities significantly predicted poor self-perceived physical and mental health, functional limitations and physical inactivity among older Indian adults. The findings further suggest that late onset of chronic diseases such as cancer and stroke and multi-morbidity had stronger associations with physical inactivity that may help identify high risk groups for screening and support.

Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries

ObjectiveTo describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status.MethodsThis was an observational, cross-sectional and multicentre study with patients who fulfilled...

Global, but not chondrocyte-specific, MT1-MMP deficiency in adult mice causes inflammatory arthritis

Membrane-type I metalloproteinase (MT1-MMP/MMP14) plays a key role in various pathophysiological processes, indicating an unaddressed need for a targeted therapeutic approach. However, mice genetically deficient in Mmp14 show severe defects in development and growth. To investigate the possibility of MT1-MMP inhibition as a safe treatment in adults, we generated global Mmp14 tamoxifen-induced conditional knockout (Mmp14kd) mice and found that MT1-MMP deficiency in adult mice resulted in severe inflammatory arthritis. Mmp14kd mice started to show noticeably swollen joints two weeks after tamoxifen administration, which progressed rapidly. Mmp14kd mice reached a humane endpoint 6 to 8 weeks after tamoxifen administration due to severe arthritis. Plasma TNF-α levels were also significantly increased in Mmp14kd mice. Detailed analysis revealed chondrocyte hypertrophy, synovial fibrosis, and subchondral bone remodeling in the joints of Mmp14kd mice. However, global conditional knockout of MT1-MMP in adult mice did not affect body weight, blood glucose, or plasma cholesterol and triglyceride levels. Furthermore, we observed substantial expression of MT1-MMP in the articular cartilage of patients with osteoarthritis. We then developed chondrocyte-specific Mmp14 tamoxifen-induced conditional knockout (Mmp14chkd) mice. Chondrocyte MT1-MMP deficiency in adult mice also caused apparent chondrocyte hypertrophy. However, Mmp14chkd mice did not exhibit synovial hyperplasia or noticeable arthritis, suggesting that chondrocyte MT1-MMP is not solely responsible for the onset of severe arthritis observed in Mmp14kd mice. Our findings also suggest that highly cell-type specific inhibition of MT1-MMP is required for its potential therapeutic use.