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ID PMID Title PublicationDate abstract
34902113 Association Between Janus Kinase Inhibitors Therapy and Mental Health Outcome in Rheumatoi 2022 Apr INTRODUCTION: Rheumatoid arthritis (RA) is a chronic debilitating illness, usually associated with mental health ailments. Literature reports contradictory observations about the association between recent RA pharmacotherapies and mental health. We systematically reviewed RA randomized control trials to synthesize the association between Janus kinases (JAK) inhibitors therapy and mental health. METHODS: We systematically searched clinical trials of JAK inhibitor intervention reporting mental health outcomes using short form-36 (SF-36) in PubMed, Embase, and Scopus databases from inception to February 2021. We have selected the studies and extracted the data, adhering to Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We have pooled the mean change of SF-36 mental component score (MCS) between JAK inhibitors and comparator therapy with a 95% confidence interval. RESULTS: Of the 2915 searched studies for systematic review, 19 studies involving 14,323 individuals were included for the meta-analysis. The pooled mean reduction in SF-36 MCS scores (after minus before) with JAK inhibitors was 4.95 (4.41-5.48). The pooled mean difference of incremental mean change in SF-36 MCS score between JAK monotherapy and comparator was 1.53 (0.88-2.18). The improvement in SF-36 MCS scores with JAK inhibitor therapy is greater than the minimum clinically important difference (MCID) value of 2.5. However, on separate analysis with comparator drugs like methotrexate and standard treatment, the MCS scores did not exceeded the MCID value and were also not statistically significant. CONCLUSIONS: JAK inhibitors results in clinically meaningful improvement in the mental health scores of the RA patients. PROSPERO REGISTRATION ID: 2021 CRD42021234466.
35026421 Pain-like behavior in the collagen antibody-induced arthritis model is regulated by lysoph 2022 Mar Inflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain, and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA(1/3) receptor inhibitor, but joint inflammation was not affected. Autotaxin, an LPA synthesizing enzyme was upregulated in dorsal root ganglia (DRG) neurons during both CAIA phases, but not in joints or spinal cord. Late-phase pronociceptive neurochemical changes in the DRG were blocked in Lpar1 receptor deficient mice and reversed by LPA neutralization. In vitro and in vivo studies indicated that LPA regulates pain-like behavior via the LPA(1) receptor on satellite glia cells (SGCs), which is expressed by both human and mouse SGCs in the DRG. Furthermore, CAIA-induced SGC activity is reversed by phospholipid neutralization and blocked in Lpar1 deficient mice. Our findings suggest that the regulation of CAIA-induced pain-like behavior by LPA signalling is a peripheral event, associated with the DRGs and involving increased pronociceptive activity of SGCs, which in turn act on sensory neurons.
35603219 Correlation Between Salivary Microbiome of Parotid Glands and Clinical Features in Primary 2022 Recent studies have demonstrated that the oral microbiome in patients with Sjögren's syndrome (SS) is significantly different from that in healthy individuals. However, the potential role of the oral microbiome in SS pathogenesis has not been determined. In this study, stimulated intraductal saliva samples were collected from the parotid glands (PGs) of 23 SS and nine non-SS subjects through PG lavage and subjected to 16S ribosomal RNA amplicon sequencing. The correlation between the oral microbiome and clinical features, such as biological markers, clinical manifestations, and functional and radiological characteristics was investigated. The salivary microbial composition was examined using bioinformatic analysis to identify potential diagnostic biomarkers for SS. Oral microbial composition was significantly different between the anti-SSA-positive and SSA-negative groups. The microbial diversity in SS subjects was lower than that in non-SS sicca subjects. Furthermore, SS subjects with sialectasis exhibited decreased microbial diversity and Firmicutes abundance. The abundance of Bacteroidetes was positively correlated with the salivary flow rate. Bioinformatics analysis revealed several potential microbial biomarkers for SS at the genus level, such as decreased Lactobacillus abundance or increased Streptococcus abundance. These results suggest that microbiota composition is correlated with the clinical features of SS, especially the ductal structures and salivary flow, and that the oral microbiome is a potential diagnostic biomarker for SS.
35511824 Dental follicle mesenchymal stem cells ameliorated glandular dysfunction in Sjögren's syn 2022 OBJECTIVE: Dental mesenchymal stem cells (MSCs) are potential for use in tissue regeneration in inflammatory diseases due to their rapid proliferating, multilineage differentiation, and strong anti-inflammatory features. In the present study, immunoregulatory and glandular tissue regeneration effects of the dental follicle (DF)MSCs in Sjögren's Syndrome (SS) were investigated. METHODS: Dental follicle (DF) tissues were obtained from healthy individuals during tooth extraction, tissues were digested enzymatically and DFMSCs were cultured until the third passage. DFMSCs were labeled with Quantum dot 655 for cell tracking analysis. The induction of the SS mouse model was performed by the injection of Ro60-273-289 peptide intraperitoneally. DFMSCs were injected intraperitoneally, or into submandibular, or lacrimal glands. Splenocytes were analyzed for intracellular cytokine (IFN-γ, IL-17, IL-10) secretion in T helper cells, lymphocyte proliferation, and B lymphocyte subsets. Histologic analysis was done for submandibular and lacrimal glands with hematoxylin-eosin staining for morphologic examination. RESULTS: The systemic injection of DFMSCs significantly reduced intracellular IFN-γ and IL-17 secreting CD4+ T cells in splenocytes (p<0.05), and decreased inflammatory cell deposits and fibrosis in the glandular tissues. DFMSCs differentiated to glandular epithelial cells in submandibular and lacrimal injections with a significant reduction in lymphocytic foci. The results showed that few amounts of DFMSCs were deposited in glandular tissues when applied intraperitoneally, while high amounts of DFMSCs were located in glandular tissues and differentiated to glandular epithelial cells when applied locally in SS murine model. CONCLUSION: DFMSCs have the potential for the regulation of Th1, Th17, and Treg balance in SS, and ameliorate glandular dysfunction. DFMSCs can be a beneficial therapeutic application for SS.
34611842 Primary Sjögren's syndrome (pSS)-related cerebellar ataxia: a systematic review and meta- 2022 Apr BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates of the exocrine glands, particularly the salivary and lacrimal glands, resulting in oral and ocular dryness. pSS has been linked to various neurological manifestations, including cerebellar dysfunction. We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related cerebellar ataxia. METHODS: A systematic literature search in the PubMed database was performed and 19 papers were eligible to be included in this paper. RESULTS: The pooled prevalence of cerebellar ataxia in pSS is estimated to be 1.5% (95% CI 0.3-6.8%). pSS patients with cerebellar involvement have a female-to-male ratio of 6:1. Although most of the patients are adults in their fifth decade of life when diagnosed, cases of children with pSS and cerebellar involvement have been reported. Typical cerebellar ataxia related to pSS manifests with vermian dysfunction, namely gait ataxia and/or cerebellar speech. Cerebellar ataxia due to pSS may also mimic degenerative cerebellar ataxia, especially when the onset is progressive. CONCLUSIONS: The diagnostic approach to a patient with cerebellar ataxia of unknown etiology should include evaluation for an underlying pSS. A thorough history and clinical examination, antibody testing, brain MRI imaging and/or MRS of the cerebellum will assist in establishing the diagnosis. Setting up a joint neuro-rheumatology clinic can be valuable given that rheumatic and neurological diseases share comorbidities.
35606782 Circulating Th2 cell reduction and Th1/Th2 imbalance are correlated with primary Sjogren's 2022 May 23 OBJECTIVE: Primary Sjogren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes. METHODS: Eighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry. RESULTS: The pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS. CONCLUSION: Decreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients.
35585979 Impression Cytology and In Vivo Confocal Microscopy of Lip Mucosa Compared With Labial Gla 2022 PURPOSE: The study assessed the validity of impression cytology (IC) and in vivo confocal microscopy (IVCM) of lip mucosa compared with labial gland biopsy, anti-Sjögren's syndrome A (SSA)/Ro antibody status, and classification criteria in suspected primary Sjögren's syndrome (pSS) patients. METHODS: Clinically suspected pSS patients (n = 201) were enrolled consecutively and were divided into pSS (n = 56) and control (n = 145, only with dryness) groups according to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. All patients underwent lip mucosa IC (inflammatory cell density) and IVCM (epithelium/intrinsic layer thickness and labial gland density/diameter) analyses. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed. RESULTS: The absolute agreement between positive lip mucosal IC (≥50 cells/4 mm(2)) and the ACR-EULAR criteria (94.5%)/labial gland biopsy (95.5%) was good, with sensitivities of 82.1 and 85.2%, respectively, and a specificity of 99.3%. Compared with controls, IVCM revealed significant lip mucosal atrophy and glandular decreases in the pSS group (all P = 0.000). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤128 μm and a gland diameter ≤114 μm were 85.7 and 89.3%; the specificities were 90.3 and 95.9%, respectively. A combination of positive IC/IVCM and anti-SSA/Ro antibody results showed a high predictive value for diagnosing pSS. CONCLUSIONS: IC and IVCM could detect distinctive cellular and morphological changes in the lip mucosa of patients with pSS. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsy for diagnosing pSS.
35140286 Different perception of dry eye symptoms between patients with and without primary Sjogren 2022 Feb 9 Here, we investigated the different perception of dry eye symptoms between in patients with and without primary Sjogren's syndrome (pSS). In this study, 221 patients with dry eye disease (DED) without pSS (non-SS DED group) and 55 patients with DED with pSS (SS DED group) were included. The ocular discomfort was evaluated using ocular surface disease index (OSDI) questionnaire and patients were further divided into 3 severity subgroups according to OSDI scores. The OSDI score was higher in the non-SS DED group even after matching corneal erosion scores despite the ocular surface erosions and tear deficiency was worse in the SS DED group. The corneal sensitivity was nearly normal in both groups without inter-group difference (Non-SS DED group: 5.82 ± 0.54 cm, SS DED group: 5.90 ± 0.29 cm, p = 0.217). Moreover, all clinical parameters were not significantly correlated with OSDI scores in both non-SS DED group and SS DED group. In the mild and severe OSDI subgroups, the ocular surface erosions and tear deficiency were worse in the SS DED group whereas the OSDI scores were not different between groups. In conclusion, clinicians should be aware that pSS patients may complain less of their discomfort unlike their actual severe status of DED.
34374853 The association between oral dryness and use of dry-mouth interventions in Sjögren's synd 2022 Feb OBJECTIVE: Sjögren's syndrome patients use different dry-mouth interventions for the relieve of their oral dryness. Recently, it was shown that patients with dry-mouth complaints have regional differences in perceived intra-oral dryness. Therefore, the aim of the present study was to investigate whether the use of dry-mouth interventions is related to the perceived regional oral dryness. MATERIALS AND METHODS: A cross-sectional study was performed among Sjögren's patients. Volunteers could anonymously administer various questionnaires, including the Regional Oral Dryness Inventory (RODI), Xerostomia Inventory (XI), Bother Index (BI) and a list of dry-mouth interventions. RESULTS: Sjögren's syndrome patients use a wide variety for the relieve of oral dryness. "Drinking water'' and "moistening the lips'' were used most frequently. Dry-mouth interventions, "drinking water'', "rinsing of the mouth", and "drinking small volumes" had significant associations with the RODI-scores of the posterior palate, and anterior and posterior tongue, respectively. On the other hand, "using mouth gel'' had a significant association with the RODI-scores of the inside cheeks. CONCLUSION: Sjögren's syndrome patients are more likely to use mouth gels when their inside cheeks were experienced as most dry, while they drank water, rinsed their mouth or drank small volumes if the posterior palate, and anterior and posterior tongue were considered as dry. It can be concluded that intra-oral dryness affects dry-mouth perception and thereby also the use of the various dry-mouth interventions. CLINICAL RELEVANCE: The therapeutic choice of dry-mouth interventions by Sjögren's syndrome patients seems to some extent to be related to dryness at specific intra-oral regions.
35384513 [Chronic Tropheryma whipplei infection: an important differential diagnosis of refractory 2022 Apr 6 BACKGROUND: Refractory arthritis is a common problem in routine rheumatology practice, and can be a diagnostic challenge. In these cases, chronic Tropheryma whipplei (T. whipplei) infection is an important differential diagnosis that should be considered. OBJECTIVE: Based on five clinical cases, this case-based review describes the diagnostic and therapeutic principles in the management of chronic T. whipplei infection. RESULTS: Whipple's disease is a multisystemic infectious disease caused by the bacterium T. whipplei. The disease typically manifests with arthralgia, weight loss and diarrhoea. Joint involvement often develops years before gastrointestinal symptoms occur. In addition to systemic manifestations ("classic Whipple's disease"), T. whipplei can also lead to localized joint infections without gastrointestinal involvement. Articular manifestations of systemic and localized T. whipplei infections are commonly misdiagnosed as a sign of various forms of autoimmmune arthritis. DISCUSSION: Whipple's disease and localized T. whipplei joint infection should be considered in the diagnostic work-up of refractory arthritis. Synovial fluid analysis by means of specific polymerase chain reaction-based testing for T. whipplei is diagnostically ground-breaking.
34499196 Serum VEGF-C as an evaluation marker of disease activity in adult-onset Still's disease. 2022 Jan In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.
35623639 Inflammatory correlates of the Patient Global Assessment of Disease Activity vary in relat 2022 May 27 OBJECTIVE: To investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status. METHODS: 1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson's coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission). RESULTS: In patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30-0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18-0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status. CONCLUSIONS: In the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.
31424836 Etanercept. 2022 Jan Etanercept is a medication used to manage and treat autoimmune conditions such as plaque psoriasis, rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis. It is a biologic fusion protein in the TNF blocker class of medications. This activity describes the indications, action, and contraindications for etanercept as a valuable agent in managing these diseases and other disorders when applicable. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team in the management of patients with psoriasis, autoimmune arthritis, and related conditions.
34976733 Exploring the translational potential of clusterin as a biomarker of early osteoarthritis. 2022 Jan BACKGROUND: Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer's disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. METHODS: In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). RESULTS: Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. CONCLUSION: There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.
35567479 Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulner 2022 May 14 OBJECTIVES: Investigate whether individuals with inflammatory arthritis, their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, U.K. METHODS: Retrospective, population-based cohort study using linked, anonymised electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases. RESULTS: A total of 1,966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1,966/56 914) in IA, vs 6% in the general population (166 602/2,760 442), (difference: 2.5%, 95% CI: 2.4% to 2.7%, p = <0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18-1.64, p= 0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40-1.64, p = <0.001), hospitalisation for previous infections (HR: 1.20, 95% CI: 1.12-1.28, p = <0.001), hospitalisations one year pre-pandemic (HR: 1.34, 95% CI: 1.25-1.44, p = <0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09-1.25, p = <0.001). CONCLUSIONS: Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.
35400368 Rheumatic Complications of Immune Checkpoint Inhibitors. 2022 May Immune checkpoint inhibitors activate the immune system to combat cancer. In doing so, however, they can cause immune-related adverse events (irAEs), including rheumatic syndromes, such as inflammatory arthritis, polymyalgia rheumatica, and myositis. This article reviews rheumatic irAEs that may be encountered in the general medicine practice and provides guidance to support prompt recognition, referral, and treatment of these patients.
35046674 Development of Rheumatoid Arthritis in Cavitary Mycobacterium avium Pulmonary Disease: A C 2022 BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) often develops in patients with rheumatoid arthritis (RA), especially during immunosuppressive treatment, including biological disease-modifying antirheumatic drugs. NTM-PD is associated with airway lesions such as bronchiectasis, which is frequently seen in RA patients. Distinguishing which diseases cause the pulmonary lesion is difficult. However, there are limited reports of the development of RA during the follow-up of NTM-PD and how biological agents should be administered in these conditions, especially with cavitary lesions. CASE PRESENTATION: A 62-year-old woman with hemosputum was referred to our hospital, where she was diagnosed with Mycobacterium avium pulmonary disease. She began treatment with several antibiotics, including clarithromycin, ethambutol, rifampicin, and amikacin. In the course of treatment, M. avium became macrolide-resistant. Five years after beginning antibiotic treatment, she felt arthralgia in the fingers and wrists and had a high titer of rheumatoid factor and anticitrullinated peptide antibody, with which we diagnosed RA. Methotrexate, prednisolone, and iguratimod were subsequently administered, but the activity of RA gradually worsened. Meanwhile, M. avium changed to a macrolide-susceptible strain, her sputum smear results remained almost negative, and the NTM-PD disease was well controlled with antimicrobial therapy, despite her having cavitary lesions. Therefore, we started using CTLA4-Ig (abatacept). RA symptoms were substantially ameliorated. The pulmonary lesions and NTM-PD worsened mildly, but her pulmonary symptoms were stable. CONCLUSION: Physicians should be mindful of the etiologies of bronchiectasis, including RA, even in patients with a long-term history of treatment for bronchiectasis and NTM-PD. When NTM-PD is well controlled, even with remaining cavitary lesions, abatacept may be an option for patients with RA based on a comprehensive assessment of disease progression using NTM sputum smear/culture, computed tomography findings, and treatment response.
35377444 Pre-defined gene co-expression modules in rheumatoid arthritis transition towards molecula 2022 Apr 4 BACKGROUND: No reliable biomarkers to predict response to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients currently exist. The aims of this study were to replicate changes in gene co-expression modules that were previously reported in response to TNFi therapy in RA; to test if changes in module expression are specific to TNFi therapy; and to determine whether module expression transitions towards a disease-free state in responding patients. METHOD: Published transcriptomic data from the whole blood of disease-free controls (n = 10) and RA patients, treated with the TNFi adalimumab (n = 70) or methotrexate (n = 85), were studied. Treatment response was assessed using the EULAR response criteria following 3 or 6 months of treatment. Change in transcript expression between pre- and post-treatment was recorded for previously defined modules. Linear mixed models tested whether modular expression after treatment transitioned towards a disease-free state. RESULTS: For 25 of the 27 modules, change in expression between pre- and post-treatment in the adalimumab cohort replicated published findings. Of these 25 modules, 6 transitioned towards a disease-free state by 3-months (p < 0.05), irrespective of clinical response. One module (M3.2), related to inflammation and TNF biology, significantly correlated with response to adalimumab. Similar patterns of modular expression, with reduced magnitude, were observed in the methotrexate cohort. CONCLUSION: This study provides independent validation of changes in module expression in response to therapy in RA. However, these effects are not specific to TNFi. Further studies are required to determine whether specific modules could assist molecular classification of therapeutic response.
35604436 Treatment of rheumatoid arthritis with conventional, targeted and biological disease-modif 2022 May 23 Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug-induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs.
35499817 Abnormalities of Peripheral Lymphocyte Subsets in Rheumatoid Arthritis Patients Complicate 2022 May 2 INTRODUCTION: Osteoporosis (OP) is one of the major comorbidities of rheumatoid arthritis (RA). Recent studies have shown that immune cells modulate bone health and regulate bone remodeling. However, the alterations of lymphocyte subsets in RA patients with OP are unclear. Here, we assessed the absolute numbers and proportions of the subsets in RA sufferers with OP and investigated the clinical significance. METHODS: A total of 777 RA patients and 117 gender- and age-matched healthy controls (HCs) were enrolled in this study. Patients were divided into RA-non-OP and RA-OP group according to their bone mineral density (BMD) and the history of fragility fracture. Peripheral lymphocyte subsets of participants were assessed by flow cytometry. RESULTS: Among 220 (28.31%) RA-OP patients, there were higher levels of erythrocyte sedimentation rate (ESR) (P = 0.011), C-reactive protein (CRP) (P = 0.028), rheumatoid factor (RF) (P = 0.013) and anti-cyclic citrullinated peptide antibody (ACPA) (P = 0.010), while red blood cells (RBC) (P = 0.039) were lower than those in RA-non-OP group. Compared with those of HCs and RA-non-OP group, the level of circulating Th17 cells in RA-OP patients was significantly increased (P < 0.05), while those of Tregs decreased (P < 0.01), leading to a higher ratio of Th17/Treg (P < 0.01). Notably, the level of B cells in both RA-non-OP and RA-OP group was reduced, this alteration was more obvious in patients with OP (P < 0.05). CONCLUSIONS: Immune disorders characterized by peripheral Th17/Treg imbalance and reduced B cells may contribute directly or indirectly to OP in RA, and this deserves more clinical attention.