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ID PMID Title PublicationDate abstract
35029182 Immune checkpoint inhibitor-induced refractory polyarthritis rapidly improved by sarilumab 2022 Jan 14 RATIONALE: Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography. PATIENT CONCERNS: A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion. DIAGNOSES: We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis). INTERVENTIONS: After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab. OUTCOMES: Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy. LESSONS: Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.
35198369 Paradoxical worsening of nontuberculous mycobacterial disease after the discontinuation of 2022 Antitumor necrosis factor-associated nontuberculous mycobacteria-immune reconstitution inflammatory syndrome (IRIS) has rarely been reported. An 84-year-old woman with a history of rheumatoid arthritis treated with etanercept was diagnosed with Mycobacterium avium complex (MAC) pulmonary disease six years before admission. Etanercept was discontinued two years ago because of MAC pulmonary disease progression and restarted nine months before admission because of worsening arthritis, again resulting in MAC pulmonary disease progression. Etanercept was discontinued again; however, the pulmonary disease progressed more rapidly. The condition was considered paradoxical worsening caused by IRIS due to etanercept discontinuation. The disease resolved quickly with chemotherapy for MAC.
35014920 Psoriatic arthritis, axial spondyloarthritis and rheumatoid arthritis in Norway: nationwid 2022 Jan 11 OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. METHODS: From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients ≥18 years those with ≥2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1(st) of January 2017 in the Norwegian adult population (age ≥18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. RESULTS: The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age ≥55 years. CONCLUSION: In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.
35585798 Manual acupuncture at ST36 attenuates rheumatoid arthritis by inhibiting M1 macrophage pol 2022 May 18 OBJECTIVES: Acupuncture has been found to be effective at relieving many inflammatory pain conditions, including rheumatoid arthritis (RA). We aimed to assess the anti-inflammatory potential of manual acupuncture (MA) treatment of RA using adjuvant-induced arthritic (AIA) rats and to explore the underlying mechanisms. METHODS: The anti-inflammatory and analgesic actions of MA at ST36 (Zusanli) in AIA rats were assessed using paw withdrawal latency and swelling, histological examination and cytokine detection by enzyme-linked immunoassay (ELISA). The cell-cell communication (CCC) network was analyzed with a multiplex immunoassay of 24 immune factors expressed in the inflamed joints, and the macrophage and Treg populations and associated cytokines regulated by MA were investigated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), ELISA and flow cytometry. RESULTS: MA markedly decreased heat hyperalgesia and paw swelling in AIA rats. MA-treated rats also exhibited decreased levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β) coupled with increased anti-inflammatory cytokines (IL-10, transforming growth factor (TGF)-β1) in the ankle joints at protein and mRNA levels. CCC network analysis confirmed that macrophages are of critical importance and are potential therapeutic targets in RA. Repeated treatment with MA triggered a macrophage phenotypic switch in the paws, with fewer M1 macrophages. Prominent increases in the Treg cell population and TGF-β1 in the popliteal lymph nodes demonstrated the immunomodulatory effects of MA. Furthermore, a selective TGF-β1-receptor inhibitor, SB431542, attenuated the anti-inflammatory effects of MA and MA-induced suppression of the levels of M1-released cytokines. CONCLUSION: These findings provide novel evidence that the anti-inflammatory and analgesic effects of MA on RA act through phenotypic modulation involving the inhibition of M1 macrophage polarization and an increase in the Treg cell population, highlighting the potential therapeutic advantages of acupuncture in controlling pain and ameliorating inflammatory conditions.
35221959 On the Nose: Anti-MDA-5 Dermatomyositis Manifesting as Perinasal Swelling. 2022 Jan The clinical presentation of dermatomyositis (DM) is diverse, with varied phenotypes that may be correlated with specific autoantibodies. The anti-melanoma differentiation-associated gene 5 (MDA5) antibody in DM is associated with an amyopathic phenotype of DM, with several unusual cutaneous manifestation and increased risk for rapidly progressive interstitial lung disease. Initial presentation may be subtle, but early diagnosis is key to initiation of proper immunosuppressive therapy. In this report, we describe perinasal edema and erythema as a presenting complaint of anti-MDA5 DM in an otherwise healthy 40-year-old woman. The edema began shortly after heavy sun exposure and was followed by painful papules in her hands and arthritis within a few weeks. She was found to have high titer of anti-CCP and anti-MDA5, and thus was diagnosed with DM and rheumatoid arthritis overlap. A CT chest, abdomen, and pelvis showed patchy ground-glass and interstitial opacities in bilateral lower lobes consistent with mild interstitial lung disease without evidence of malignancy. Perinasal cutaneous findings and arthralgias improved with initiation of prednisone. To our knowledge, this is the first report of perinasal edema as a presenting symptom for DM and should raise suspicion for MDA-5 disease.
35368757 Activities and Molecular Mechanisms of Diterpenes, Diterpenoids, and Their Derivatives in 2022 Diterpenes and their derivatives have many biological activities, including anti-inflammatory and immunomodulatory effects. To date, several diterpenes, diterpenoids, and their laboratory-derived products have been demonstrated for antiarthritic activities. This study summarizes the literature about diterpenes and their derivatives acting against rheumatoid arthritis (RA) depending on the database reports until 31 August 2021. For this, we have conducted an extensive search in databases such as PubMed, Science Direct, Google Scholar, and Clinicaltrials.gov using specific relevant keywords. The search yielded 2708 published records, among which 48 have been included in this study. The findings offer several potential diterpenes and their derivatives as anti-RA in various test models. Among the diterpenes and their derivatives, andrographolide, triptolide, and tanshinone IIA have been found to exhibit anti-RA activity through diverse pathways. In addition, some important derivatives of triptolide and tanshinone IIA have also been shown to have anti-RA effects. Overall, findings suggest that these substances could reduce arthritis score, downregulate oxidative, proinflammatory, and inflammatory biomarkers, modulate various arthritis pathways, and improve joint destruction and clinical arthritic conditions, signs, symptoms, and physical functions in humans and numerous experimental animals, mainly through cytokine and chemokine as well as several physiological protein interaction pathways. Taken all together, diterpenes, diterpenoids, and their derivatives may be promising tools for RA management.
34995017 The Incidence, Risk Factors, and Mortality of Clinical and Subclinical Rheumatoid Arthriti 2022 Jan 7 OBJECTIVES: 1) Identify the incidence, risk factors, and outcomes of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD); and 2) assess time-trends in the incidence and mortality of RA-ILD. METHODS: We included adult residents of Olmsted County, Minnesota with incident RA during 1999-2014. Subjects were followed until death, emigration, or 4/30/2019. ILD was defined as the presence of a radiologist-defined pattern consistent with ILD on chest CT. When chest CT was absent, the combination: 1) chest X-ray abnormalities compatible with ILD; and 2) restrictive pattern on pulmonary function testing was considered consistent with ILD. Potential risk factors included age, sex, smoking, obesity, seropositivity, extra-articular manifestations (EAMs), and medications. For survival analysis, we matched RA-ILD patients to RA-non-ILD comparators. The frequency and mortality from clinician-diagnosed RA-ILD during 1999-2014 was compared against a cohort from 1955-1994. RESULTS: During 1999-2014, 645 individuals (70% women) had incident RA; median age was 55.3 years, and 53% never smoked. Twenty-two patients had ILD before RA, and 51 (67% women) developed ILD during follow-up. The 20-year cumulative incidence of RA-ILD was 15.3%. Ever-smoking (HR=1.92), age (HR=1.89 per 10-year increase) at RA onset, and severe EAMs (HR=2.29) were associated with incident RA-ILD. The RA-ILD cases had higher mortality than their matched RA comparators (HR=2.42). Incidence of RA-ILD was non-significantly lower in 1999-2014 than 1955-1994, but mortality was improved. CONCLUSIONS: RA-ILD occurs in nearly 1 in 6 patients with RA within 20 years and is associated with shorter survival. Lack of significant change in RA-ILD incidence over 6 decades deserves further investigation.
35612872 Risk of Prostate Cancer in U.S. Veterans with Rheumatoid Arthritis. 2022 Apr 5 OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of select cancers, including lymphoma and lung cancer. Whether RA influences prostate cancer risk is uncertain. We aimed to determine the risk of prostate cancer in patients with RA compared to patients without RA in the Veterans Health Administration (VA). METHODS: We performed a matched (up to 1:5) cohort study of males with and without RA in the VA from 2000 to 2018. RA status, as well as covariates, were obtained from national VA databases. Prostate cancer was identified through linked VA cancer databases and the National Death Index. Multivariable Cox models compared prostate cancer risk between RA and non-RA, including models that accounted for retention in the VA system. RESULTS: We included 56,514 veterans with RA and 227,284 veterans without RA. During 2,337,104 patient-years of follow-up, 6,550 prostate cancers occurred. Prostate cancer incidence (per 1,000 patient-years) was 3.50 (95% CI 3.32, 3.69) in RA and 2.66 (95% CI 2.58, 2.73) in non-RA. After accounting for confounders and censoring for attrition of VA healthcare, RA was modestly associated with a higher prostate cancer risk (adjusted HR 1.12 [95% CI 1.04, 1.20]). There was no association between RA and prostate cancer mortality (adjusted HR 0.92 [95% CI 0.73, 1.16]). CONCLUSION: RA was associated with a modestly increased risk of prostate cancer, but not prostate cancer mortality, after accounting for relevant confounders and several potential sources of bias. However, even minimal unmeasured confounding could explain these findings.
35472662 Adipocytokines and achievement of low disease activity in rheumatoid arthritis. 2022 Apr 12 PURPOSE: To determine if adipocytokines are independently associated with the achievement of low disease activity (LDA) over long-term follow-up in a large rheumatoid arthritis (RA) registry. METHODS: This cohort study evaluated adults with RA from the Veteran's Affairs RA Registry. Adipocytokines (adiponectin, leptin, and fibroblast growth factor [FGF]-21) and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum from enrollment. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox proportional hazard models evaluated associations between adipocytokines and rates of 1) DAS28 LDA and remission, 2) individual Boolean remission criteria and 3) initiation of a new bDMARD or tsDMARD. RESULTS: There were 1,276 participants with a DAS28 >3.2 at enrollment. Of these, 827 achieved LDA and 598 achieved remission over 2,287 and 4,096 person-years, respectively. Patients in the highest quartile of adiponectin had lower rates LDA before and after adjustment [aHR Q4: 0.68 (0.53,0.87) p<0.001]. Those in the highest quartile of leptin and FGF-21 also had lower rates of LDA. Higher quartiles of adipocytokines were also associated with lower rates of achieving a low patient/evaluator global scores and low tender joint counts. Among 1,236 biologic-naïve participants, values above the median for adiponectin [HR: 1.67 (1.23,1.26) p = 0.001] and FGF-21 [HR: 1.27 (1.09,1.47) p = 0.002] were associated with a greater likelihood of initiating a b/tsDMARD. CONCLUSIONS: Adipocytokines may serve as prognostic biomarkers of a more severe RA disease course. Additional study is needed to determine whether adipocytokines are phenotypic markers or whether they actively promote disease progression.
35420256 Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and t 2022 Apr 14 Defects of articular joints are becoming an increasing societal burden due to a persistent increase in obesity and aging. For some patients suffering from cartilage erosion, joint replacement is the final option to regain proper motion and limit pain. Extensive research has been undertaken to identify novel strategies enabling earlier intervention to promote regeneration and cartilage healing. With the introduction of decellularized extracellular matrix (dECM), researchers have tapped into the potential for increased tissue regeneration by designing biomaterials with inherent biochemical and immunomodulatory signals. Compared to conventional and synthetic materials, dECM-based materials invoke a reduced foreign body response. It is therefore highly beneficial to understand the interplay of how these native tissue-based materials initiate a favorable remodeling process by the immune system. Yet, such an understanding also demands increasing considerations of the pathological environment and remodeling processes, especially for materials designed for early disease intervention. This knowledge will avoid rejection and help predict complications in conditions with inflammatory components such as arthritides. This review outlines general issues facing biomaterial integration and emphasizes the importance of tissue-derived macromolecular components in regulating essential homeostatic, immunological, and pathological processes to increase biomaterial integration for patients suffering from joint degenerative diseases.
35650202 Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression 2022 Jun 1 Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut-microbiota-brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer's patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut-microbiota-brain axis.
33690849 A Novel Approach for Immediate Implant-Based Oral Rehabilitation in a Sjögren's Syndrome 2022 Apr 1 Patients with Sjögren syndrome (SS) experience difficulties in wearing conventional dentures. After removal of all teeth, the oral rehabilitation is challenging and time consuming using conventional treatment protocols. Although implant-retained overdentures are beneficial for this specific patient group, the average total oral rehabilitation time (TORT) usually takes at least 9 months and needs to be reduced to increase patients' quality of life (QoL). In this paper, we report on a new treatment concept for immediate implant-based oral rehabilitation in a 77-year-old patient with partial edentulous SS. Because of persistent pain, discomfort, and retention problems with the conventional prosthetic devices, full clearance of the remaining mandibular dentition and immediate oral rehabilitation with an implant-retained overdenture were suggested. The treatment protocol included virtual surgical planning (VSP), combining a guided bone reduction of the mandibular alveolar process, immediate dental implant placement, and restoration using a prefabricated bar and placement of the overdenture. This method demands the use of ionizing 3D imaging optionally combined with an optical dental scan or a conventional impression. Furthermore, one needs to gain experience using VSP software. This novel treatment concept for immediate implant-based oral rehabilitation using VSP proved to be feasible and safe in a patient with SS, resulting in a significantly reduced TORT and improved QoL. Further research is needed to what extent this treatment concept could be beneficial to other patient groups, such as patients with head and neck cancer.
35533910 Ziyuglycoside I attenuates collagen-induced arthritis through inhibiting plasma cell expan 2022 Aug 10 ETHNOBOTANICAL RELEVANCE: With most of the anti-rheumatic drugs having severe adverse drug reactions and poor tolerance, the active components from natural herbs provides a repository for novel, safe, and effective drug development. Sanguisorba officinalis L. exhibits definite anti-inflammatory capacity, however, whether it has anti-rheumatic effects has not been revealed. AIM OF THE STUDY: In the present study, the effect of Ziyuglycoside I (Ziyu I), one of the most important active components in Sanguisorba officinalis L., was investigated in treating collagen-induced arthritis (CIA), illuminating its potential pharmacological mechanisms. MATERIAL AND METHODS: CIA mice were treated with 5, 10, or 20 mg/kg of Ziyu I or 2 mg/kg of MTX, and clinical manifestations as well as pathological changes were observed. T and B cell viability was determined using cell counting kit-8, plasma autoantibodies and cytokines were tested with ELISA, T and B cell subsets were identified by flow cytometry, Blimp1 expression was detected by RT-qPCR and in situ immunofluorescence. The expression of activation-induced cytidine deaminase (AID) was detected by immunohistochemistry. ERK activation in B cells was verified through western blotting and immunofluorescence. Meanwhile, bioinformatics retrieval and molecular docking/molecular dynamics were used to predict the relationship between Blimp1, ERK and Ziyu I with the pharmacokinetics and toxicity of Ziyu I being evaluated in the ADMETlab Web platform. RESULTS: Ziyu I treatment effectively alleviated the joint inflammatory manifestation including arthritis index, global scores, swollen joint count and body weight of CIA mice. It improved the pathological changes of joint and spleen of arthritic mice, especially in germinal center formation. Ziyu I displayed a moderate regulatory effect on T cell activation, the percentage of total T and helper T cells, and tumor necrosis factor-α, but transforming growth factor-β was not restored. Increased spleen index, B cell viability and plasma auto-antibody production in CIA mice were significantly reduced by Ziyu I therapy. Of note, we found that Ziyu I administration substantially inhibited the excessive expansion of plasma cells in spleen through preventing the expression of B lymphocyte induced maturation protein 1 (Blimp1) and AID in B cells. Ziyu I was predicted in silico to directly interact with ERK2, and reduce ERK2 activation, contributing to the depressed expression of Blimp1. Moreover, Ziyu I was predicted to have a favorable pharmacokinetic profile and low toxicity. CONCLUSION: Ziyu I effectively ameliorates CIA in mice by inhibiting plasma cell generation through prevention of ERK2-mediated Blimp1 expression in B cells. Therefore, Ziyu I is a promising candidate for anti-arthritic drug development.
34977602 Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rit 2022 Mar BACKGROUND: In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. METHODS: This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2-4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7-10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. FINDINGS: Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222-324] in responders vs 107 days [80-152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4(+) T-cell responses and 14 (74%) had CD8(+) T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4(+) and CD8(+) T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. INTERPRETATION: This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6-9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response. FUNDING: The Coalition for Epidemic Preparedness Innovations, Research Council of Norway Covid, the KG Jebsen Foundation, Oslo University Hospital, the University of Oslo, the South-Eastern Norway Regional Health Authority, Dr Trygve Gythfeldt og frues forskningsfond, the Karin Fossum Foundation, and the Research Foundation at Diakonhjemmet Hospital.
35222372 Anti-Mouse CD83 Monoclonal Antibody Targeting Mature Dendritic Cells Provides Protection A 2022 Antibodies targeting the activation marker CD83 can achieve immune suppression by targeting antigen-presenting mature dendritic cells (DC). This study investigated the immunosuppressive mechanisms of anti-CD83 antibody treatment in mice and tested its efficacy in a model of autoimmune rheumatoid arthritis. A rat anti-mouse CD83 IgG2a monoclonal antibody, DCR-5, was developed and functionally tested in mixed leukocyte reactions, demonstrating depletion of CD83(+) conventional (c)DC, induction of regulatory DC (DCreg), and suppression of allogeneic T cell proliferation. DCR-5 injection into mice caused partial splenic cDC depletion for 2-4 days (mostly CD8(+) and CD83(+) cDC affected) with a concomitant increase in DCreg and regulatory T cells (Treg). Mice with collagen induced arthritis (CIA) treated with 2 or 6 mg/kg DCR-5 at baseline and every three days thereafter until euthanasia at day 36 exhibited significantly reduced arthritic paw scores and joint pathology compared to isotype control or untreated mice. While both doses reduced anti-collagen antibodies, only 6 mg/kg achieved significance. Treatment with 10 mg/kg DCR-5 was ineffective. Immunohistological staining of spleens at the end of CIA model with CD11c, CD83, and FoxP3 showed greater DC depletion and Treg induction in 6 mg/kg compared to 10 mg/kg DCR-5 treated mice. In conclusion, DCR-5 conferred protection from arthritis by targeting CD83, resulting in selective depletion of mature cDC and subsequent increases in DCreg and Treg. This highlights the potential for anti-CD83 antibodies as a targeted therapy for autoimmune diseases.
35014229 Risk of Pregnancy Complications and Low Birth Weight Offsprings in Korean Women With Rheum 2022 Jan 10 BACKGROUND: To determine the risk of pregnancy complications and adverse offspring outcomes in Korean women with rheumatic diseases (RDs). METHODS: Women aged 20-44 years with pregnancies ending in delivery were identified from the National Health Insurance Service-National Health Information Database (2009-2016). Women with RD including systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SPRA), and ankylosing spondylitis (AS) (n = 4,284) were age-matched with controls (n = 26,023). Outcome variables included threatened abortion (TA), preterm birth (PB), preeclampsia/eclampsia (PE/E), intrauterine growth retardation (IGR), urinary tract infection, low birth weight (LBW) offsprings, and offspring death within 1 year of birth. RESULTS: Women with RDs had increased risks for cesarean section delivery (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), TA (OR, 1.4; 95% CI, 1.2-1.5), PB (OR, 2.4; 95% CI, 1.9-3.2), PE/E (OR, 4.4; 95% CI, 3.3-5.9), and IGR (OR, 2.4; 95% CI, 2.0-3.1) than the controls. The risk of pregnancy complications was increased in SLE and SPRA pregnancies but not in AS pregnancies. Offsprings of women with RDs had an increased risk of LBW (OR, 4.0; 95% CI, 3.2-4.9). The offspring mortality rate within 1 year of birth was higher in women with RDs (6.2/10,000 persons) than in the controls (4.9/10,000 persons). CONCLUSION: Women with RDs are at a risk of developing pregnancy complications, and the risk of LBW offsprings and offspring death within 1 year of birth is increased in these women. Therefore, this population requires special attention during their childbearing years.
34637968 Anti-rheumatic, and analgesic effects by the parent tuberous roots of Aconitum jaluense in 2022 May 10 AIM OF THE STUDY: The aim of this study was to test the anti-rheumatic effects of A. jaluense tubers in acute and chronic arthritis rats, and to assign its ingredients through UHPLC-TOF/MS. MATERIALS AND METHODS: Subcutaneous injection of carrageenan for acute arthritis and complete Freund's adjuvant (CFA) for chronic arthritis was carried out in the hind paw of SD rats. The paw volume was measured by a plethysmometer thermal hyperalgesia was tested using a thermal plantar tester, and mechanical hyperalgesia was evaluated by ankle flexion evoked vocalizations. The expression of c-Fos in the brain hippocampus was measured with the avidin-biotin-peroxidase technique. The ingredients were assigned by UHPLC-TOF/MS, chromatography was performed by UHPLC system with DAD detector and BEH C(18) column, and spectroscopy was conducted by ESI-MS system. RESULTS AND DISCUSSION: The 80% ethanoic extract of A. jaluense tubers showed an acute anti-inflammatory effect by suppressing the edema volume in the hind paw of carrageenan-stimulated rats. In addition, A. jaluense tubers exerted an anti-rheumatic activity by reducing the secondary swelling volume from an immunological reaction in the left hind paw of CFA-induced chronic arthritis rats. Additionally, oral treatment with the 80% ethanoic extract -showed potent analgesic effects in the arthritis rats by recovering the paw withdrawal latency stimulated by the thermal hyperalgesia and by reducing the vocalization scores evoked by ankle flexion on both hind paws. Moreover, its treatment also indicated an anti-psychiatric effect by controlling the c-Fos protein expression of the brain hippocampus in CFA-stimulated arthritis rats. These results suggested that these therapeutic effects were exhibited by less toxic mono-esterified diterpenoid alkaloids (MDAs), and nontoxic non-esterified diterpenoid alkaloids (NDAs). CONCLUSION: A. jaluense tubers may act as viable therapeutic or preventive candidates for acute and chronic arthritis, particularly, for immune-inflammatory rheumatoid arthritis to suppress the pain and psychiatric condition.
35514156 A Population-Based Study Evaluating Retention in Rheumatology Care Among Patients With Rhe 2022 May 5 OBJECTIVE: The study objective was to assess adherence to system-level performance measures measuring retention in rheumatology care and disease modifying anti-rheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). METHODS: We used a validated health administrative data case definition to identify individuals with RA in Ontario, Canada, between 2002 and 2014 who had at least 5 years of potential follow-up prior to 2019. During the first 5 years following diagnosis, we assessed whether patients were seen by a rheumatologist yearly and the proportion dispensed a DMARD yearly (in those aged ≥66 for whom medication data were available). Multivariable logistic regression analyses were used to estimate the odds of remaining under rheumatologist care. RESULTS: The cohort included 50,883 patients with RA (26.1% aged 66 years and older). Over half (57.7%) saw a rheumatologist yearly in all 5 years of follow-up. Sharp declines in the percentage of patients with an annual visit were observed in each subsequent year after diagnosis, although a linear trend to improved retention in rheumatology care was seen over the study period (P < 0.0001). For individuals aged 66 years or older (n = 13,293), 82.1% under rheumatologist care during all 5 years after diagnosis were dispensed a DMARD annually compared with 31.0% of those not retained under rheumatology care. Older age, male sex, lower socioeconomic status, higher comorbidity score, and having an older rheumatologist decreased the odds of remaining under rheumatology care. CONCLUSION: System-level improvement initiatives should focus on maintaining ongoing access to rheumatology specialty care. Further investigation into causes of loss to rheumatology follow-up is needed.
35464810 Is there still a place for methotrexate in severe psoriatic arthritis? 2022 The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient's decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.
35198942 Aggressive Cholesterol Pericarditis With Minimal Effusion Masquerading as Treatment-Refrac 2022 Feb A middle-aged woman with rheumatoid arthritis presented with treatment-refractory pericarditis. Symptoms persisted despite escalation of immunosuppression, and she had recurrent admissions for heart failure. Imaging revealed minimal pericardial effusion and a thickened pericardium. Invasive hemodynamics confirmed constrictive physiology, and a pericardiectomy was required. Pathology testing confirmed cholesterol pericarditis, a rare condition of inflammatory cholesterol deposits within the pericardium. Previous reports describe moderate-to-large volumes of gold-coloured pericardial fluid. This case illustrates that cholesterol pericarditis can present with minimal pericardial effusion and rapidly progress to pericardial constriction.