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ID PMID Title PublicationDate abstract
35084302 Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass 2022 Jan 12 OBJECTIVES: To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. METHODS: This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. RESULTS: A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. CONCLUSIONS: Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.
35048793 Cost-effectiveness of a telehealth intervention in rheumatoid arthritis: economic evaluati 2022 Jan 20 OBJECTIVE: Telehealth is rapidly gaining ground from usual treatment, not least because of coronavirus disease 2019 (COVID-19) measures. Within rheumatology, telehealth has been used for, inter alia, follow-up for patients with rheumatoid arthritis (RA) with low disease activity or in remission. This study aims to assess the cost-effectiveness of such a telehealth intervention. METHOD: In a randomized controlled trial, 294 patients were randomized into patient-reported outcome-based telehealth follow-up by either a nurse (PRO-TN) or a rheumatologist (PRO-TR) or to conventional outpatient follow-up (control). Cost-effectiveness was evaluated using costs per quality-adjusted life-year (QALY) gained. Individual-level healthcare and productivity costs were retrieved from national Danish registers. Incremental cost-effectiveness ratios were calculated for the intervention groups compared to the control group. Bootstrapping with 10 000 replications was used to obtain confidence intervals. Furthermore, cost-effectiveness acceptability curves were generated. RESULTS: The cost comparison showed that PRO-TR was significantly less costly than the control group, whereas the relative reduction in costs for PRO-TN was not significant. The telehealth groups experienced minor, non-significant declines in QALYs, whereas the control group experienced a slight, non-significant increase. The cost-effectiveness analysis showed that for PRO-TR, the willingness to accept a QALY loss was 89 328 EUR. A similar but smaller and non-significant result was seen for PRO-TN. CONCLUSION: PRO-TR and PRO-TN seem to cost less but provide broadly similar health outcomes compared with conventional follow-up. Between the intervention groups, PRO-TR was significantly less costly. More studies are needed to conclude whether rheumatologist- or nurse-led telehealth is more cost-effective than conventional follow-up.
35583256 ACPA-negative and ACPA-positive RA-patients achieving disease resolution demonstrate disti 2022 May 18 OBJECTIVES: Although sustained DMARD-free remission (SDFR; sustained absence of clinical-synovitis after DMARD-discontinuation) is increasingly achievable in RA, prevalence differs between ACPA-negative(40%) and ACPA-positive-RA(5-10%). Additionally, early DAS-remission (DAS4months<1.6) is associated with achieving SDFR in ACPA-negative, but not in ACPA-positive-RA. Based on these differences, we hypothesized that longitudinal patterns of local tissue-inflammation (synovitis/tenosynovitis/osteitis) also differ between ACPA-negative and ACPA-positive RA-patients achieving SDFR. With the ultimate aim to increase understanding of disease-resolution in RA, we studied MRI-detected joint-inflammation over time in relation to SDFR-development in ACPA-positive-RA and ACPA-negative-RA. METHODS: 198 RA-patients (94 ACPA-negative, 104 ACPA-positive) underwent repeated MRIs (0/4/12/24-months) and were followed on SDFR-development. The course of MRI-detected total-inflammation, and synovitis/tenosynovitis/osteitis individually, were compared between RA-patients who did and did not achieve SDFR, using Poisson-mixed-models. 174 ACPA-positive RA-patients from the AVERT-1 were studied as ACPA-positive validation-population. RESULTS: In ACPA-negative-RA, baseline MRI-detected inflammation-levels of patients achieving SDFR were similar to patients without SDFR, but declined 2.0-times stronger in the first year of DMARD-treatment (IRR 0.50 [95%CI; 0.32-0.77]; p< 0.01). This stronger decline was seen in tenosynovitis/synovitis/osteitis. In contrast, ACPA-positive RA-patients achieving SDFR, had already lower inflammation-levels (especially synovitis/osteitis) at disease-presentation (IRR 0.45 [95%CI; 0.24-0.86]; p= 0.02) compared with patients without SDFR, and remained lower during subsequent follow-up (p= 0.02). Similar results were found in the ACPA-positive validation-population. CONCLUSION: Compared with RA-patients without disease-resolution, ACPA-positive RA-patients achieving SDFR have less severe joint-inflammation from diagnosis onwards, whilst ACPA-negative RA-patients present with similar inflammation-levels but demonstrate a stronger decline in the first year of DMARD-therapy. These different trajectories suggest different mechanisms underlying resolution of RA-chronicity in both RA-subsets.
35214603 Training Physicians in Motivational Communication to Address Influenza Vaccine Hesitation: 2022 Jan 19 BACKGROUND: Strategies to support health care professionals on how to address vaccine hesitancy are needed. METHODS: We developed a 4-h Motivational Communication (MC) training program tailored to help physicians address hesitancy related to influenza vaccination among patients living with rheumatoid arthritis. Five MC competencies were evaluated at baseline and post-training with a standardized patient using the Motivational Interviewing Treatment Integrity [MITI] scale. Adherence to MC during clinical consultations and changes in vaccine intentions was measured as secondary outcomes. RESULTS: Seven rheumatology physicians participated in the training. MITI scores increased in all participants, and 71% (n = 5) achieved thresholds of clinical competency (i.e., ≥3.5/5 at MITI global score and ≥3/5 on at least 3 individual competency score) post-training. Autonomy/support and empathy competencies reached competency thresholds (+2.4 ± 1.3 to +4.1 ± 0.7 and +2.1 ± 0.7 to +4.1 ± 0.7, respectively). Evocation and collaboration competencies improved but without reaching competency thresholds (+1.4 ± 0.8 to +3.1 ± 1.1; +1.4 ± 0.8 to +2.9 ± 1.1, respectively). Direction did not improve. Among 21 patient consultations post-training, 15 (71%) were MC-consistent. Of the 15 patients, 67% (10/15) intended to receive the influenza vaccine and 33% (5/15) received it. CONCLUSION: A brief MC training program targeting vaccine hesitancy increased MC competency among rheumatology physicians and promoted behavioral change among patients.
35643951 The efficacy of short-term bridging strategies with high- and low-dose prednisolone on rad 2022 May 29 OBJECTIVE: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. We compare the effect of three bridging strategies including high-dose and low-dose prednisolone on radiographic and clinical outcomes. METHODS: Adult RA patients from one rheumatology hospital and 23 rheumatology practices presenting with moderate/high disease activity were randomised (1:1:1) to 60 mg (high-dose, HDP), 10 mg prednisolone (low-dose, LDP) daily (tapered to 0 mg within 12 weeks), or placebo. The 12-week-intervention period was followed by 40 weeks of therapy at physicians' discretion. The primary outcome was radiographic change at 1 year measured by the modified Sharp/van der Heijde (mSvdH) score. Disease activity was assessed by DAS28 (ESR). RESULTS: Of 395 randomized patients (n=132 HDP, n=131 LDP, n=132 placebo), 375 (95%) remained in the modified intention-to-treat analysis. Mean changes (standard deviation) in mSvdH scores of the 3 groups after one year were comparable: HDP 1.0 (2.0), LDP 1.1 (2.2), placebo 1.1 (1.5) units. The primary analysis showed no superiority of HDP vs. placebo (estimated difference of the mean change -0.04 (95% confidence interval (CI) -0.5; 0.4)). At week 12, mean DAS28 (ESR) differed: HDP vs. placebo: -0.6 (95%CI -1.0; -0.2); LDP vs. placebo: -0.8 (95% CI -1.2; -0.5). At week 52, there was no significant difference in DAS28 (ESR) between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often. CONCLUSION: Short-term glucocorticoid bridging therapy at high dose showed no benefit with regard to progression of radiographic damage at one year.
34474172 Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic re 2022 Jan OBJECTIVES: The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. METHODS: Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. RESULTS: Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I(2) = 90%) as compared to a single dose (69.3, 52.4-82.3, I(2) = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I(2) = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I(2) = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I(2) = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I(2) = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I(2) = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I(2) = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. CONCLUSION: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.
35583855 Chemical constituents, biological activities and anti-rheumatoid arthritic properties of f 2022 May 18 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with predominant synovitis that has no complete cure or preventive treatment. Citrus essential oils, used in natural fragrances, contain a variety of functional ingredients that are worthy of investigation for their potential as natural anti-inflammatory drug sources. In this study, essential oils were hydro distilled from the peels of four citrus species: Citrus sinensis (L.) Osbeck (CSEOs), Citrus paradisi Macfad. (CPEOs), Citrus limon (L.) Osbeck (CLEOs) and Citri Reticulatae Pericarpium (CREOs). Altogether, 81 compounds were identified using gas chromatography-mass spectrometry (GC-MS), of which d-limonene (17.96%-94.66%) was an abundant component of all four oils. The stable 1,1-diphenyl-2-pyrrole hydrazine (DPPH) free radical test showed that all four essential oils had excellent antioxidant properties (IC(50) , 0.76-13.86 μg/mL). Furthermore, the oils remarkably increased the first G1 phase of the cell cycle, which inhibited the pro-inflammatory factor expression. An immunohistochemical analysis indicated that the four essential oils inhibited the expression of tumor necrosis factor-α and cyclooxygenase-2 and they exhibited anti-inflammatory activity in a rat model that was similar to that of the common drug, Ibuprofen. These results show that the CSEOs, CPEOs, CLEOs, and CREOs have significant antirheumatic activities and thus have great potential in developing functional food or drugs for treating RA.
35430901 Systematic analysis of inflammation and pain pathways in a mouse model of gout. 2022 Jan Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. However, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystal-induced gout model, we performed genome-wide transcriptome analysis of the inflamed ankle joint, dorsal root ganglion (DRG), and spinal cord of gouty mice. Our results revealed important transcriptional changes, including highly elevated inflammation and broad activation of immune pathways in both the joint and the nervous system, in gouty mice. Integrated analysis showed that there was a remarkable overlap between our RNAseq and human genome-wide association study (GWAS) of gout; for example, the risk gene, stanniocalcin-1 (STC1) showed significant upregulation in all three tissues. Interestingly, when compared to the transcriptomes of human osteoarthritis (OA) and rheumatoid arthritis (RA) joint tissues, we identified significant upregulation of cAMP/cyclic nucleotide-mediated signaling shared between gouty mice and human OA with high knee pain, which may provide excellent drug targets to relieve gout pain. Furthermore, we investigated the common and distinct transcriptomic features of gouty, inflammatory pain, and neuropathic pain mouse models in their DRG and spinal cord tissues. Moreover, we discovered distinct sets of genes with significant differential alternative splicing or differential transcript usage in each tissue, which were largely not detected by conventional differential gene expression analysis approaches. Based on these results, our study provided a more accurate and comprehensive depiction of transcriptomic alterations related to gout inflammation and pain.
35040437 Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional 2022 Jan 18 Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia. Many conventional drugs also require in vivo metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be heterogeneous between patients. New therapeutic technologies and research have highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional antiinflammatory therapies. This Review highlights the role of lipid metabolism in inflammation and in the mechanisms of action of AIRD therapeutics. Opportunities for cotherapies targeting lipid metabolism that could reduce immunometabolic complications and potential increased cardiovascular disease risk in patients with AIRDs are discussed.
34728318 SZAP exerts analgesic effects on rheumatalgia in CIA rats by suppressing pain hyperalgesia 2022 Feb 10 ETHNOPHARMACOLOGICAL RELEVANCE: ShexiangZhuifeng Analgesic Plaster (SZAP) is a traditional Chinese medicine and transdermal formulation composed of many Chinese herbs and active compounds. SZAP was recently approved by the China Food and Drug Administration for the treatment of pain associated with osteoarticular diseases and is preferred by most rheumatoid arthritis patients in China. However, its mechanism has not been elucidated in detail. AIM OF THE STUDY: We sought to determine the analgesic effect of SZAP in collagen-induced arthritis (CIA) rats and explore the underlying mechanisms of pain transmission, such as via the TRPV1 and P2X3 receptors. METHODS: After CIA was established, rats were treated with SZAP for 7 days. Paw thickness, arthritis score, and haematoxylin and eosin staining were used to evaluate the effectiveness of SZAP. Paw withdrawal threshold (PWT) and tail-flick latency (TFL) were used to estimate the analgesic effect of SZAP. The levels of PGE(2), BK, 5-HT, SP, and CGRP in the serum and synovium were determined using ELISA kits, and ATP in the synovium was measured using HPLC. The expression of TRPV1 and P2X3 in the DRG was detected using western blotting and immunofluorescence. TRPV1 and P2X3 agonists were further used to determine the analgesic effects of SZAP on CIA rats based on PWT and TFL. RESULTS: SZAP not only significantly ameliorated arthritis scores and paw thickness by improving the pathological damage of synovial joints, but also remarkably alleviated pain in CIA rats. Further, treatment with SZAP significantly reduced peripheral 5-HT, PGE(2) BK, SP, CGRP, and ATP. Additionally, the expression of TRPV1 and P2X3 in the DRG was markedly downregulated by SZAP. Interestingly, the analgesic effect of SZAP was weakened (reduction of PWT and TFL) when TRPV1 and P2X3 were activated by capsaicin or α,β-meATP, respectively. CONCLUSION: SZAP ameliorates rheumatalgia by suppressing hyperalgesia and pain transmission through the inhibition of TRPV1 and P2X3 in the DRG of CIA rats.
35260197 Post-chikungunya arthritis: a longitudinal study in a tertiary care hospital in Bangladesh 2022 Mar 8 BACKGROUND AND OBJECTIVE: To identify the clinical patterns and consequences of post-chikungunya arthritis was the study's objective. METHODS: This longitudinal study was carried out among 143 Chikungunya virus (CHIKV) infected adult patients at the rheumatology department, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, during the outbreak of CHIKV infection in 2017. The disease was categorized into three phases: acute or febrile (lasting up to 10 days), subacute (11-90 days), and chronic (> 90 days). Patients who progressed towards the chronic phase were followed up to 1-year. Post-CHIKV de novo chronic inflammatory rheumatisms (CIRs) were characterized by persistent mono or oligoarthritis, undifferentiated polyarthritis, or meet the criteria rheumatoid arthritis (RA) or Spondyloarthritis (SpA). In addition, functional status was assessed by the validated Bangla version of the Health Assessment Questionnaire (HAQ). RESULTS: Mean age was 43.3 ± 11.5 years, and 51.0% were male. Within 1-year follow-up, 60 (41.9%) patients were suffering from arthralgia/ arthritis. Of them 52 patients did not have any pre-existing arthralgia/arthritis. 35 (65.3%) had undifferentiated arthritis, 10 (19.2%) had SpA, and 7 (13.5%) had RA. Patients with pre-existing rheumatological disorders, 6(4.2%) had SpA, 1(0.7%) had RA and 1(0.7%) had osteoarthritis. Polyarthralgia (n = 33, 55.0%) and polyarthritis (n = 20, 33.3%) were the main presentations. Female gender (OR: 0.45; CI: 0.21-0.96), positive IgG (OR: 0.30; CI: 0.12-0.76), and moderate to severe functional disability (OR: 3.46; CI: 1.62-7.40) were independent predictors of developing chronic post-CHIKV rheumatism. CONCLUSIONS: At 1-year follow-up, more than one-third of the patients remained symptomatic. Female gender, positive IgG, and moderate to severe functional disability contributed to the development of chronicity.
35123211 Enhanced type I interferon signature induces neutrophil extracellular traps enriched in mi 2022 Feb Adult-onset Still's disease (AOSD) is a rare but clinically well-known auto-inflammatory disorder. Cytokine storm, the hallmark of AOSD, is mediated by neutrophil hyperactivation and enhanced neutrophil extracellular trap (NET) formation. Type I interferons (IFNs), having a primary role in the initiation of proinflammation responses, can induce subsequent inflammatory cytokine production. However, the role of type I IFNs in AOSD is unclear. Indeed, high levels of IFN-α and IFN-β expression are presented by AOSD patients. In this investigation, hierarchical unsupervised clustering was performed on IFN-α and IFN-β data to identify a cluster of AOSD patients who had a serious condition. Neutrophils from treatment-naïve active AOSD patients showed very strong enrichment in their IFN-α response, as shown by RNA-seq and confirmed by the IFN score. Whether IFN-α stimulates NET formation was also tested. IFN-α had the ability to form NETs that contained oxidized mitochondrial DNA (ox-mtDNA). Moreover, the JAK inhibitor could be used to dampen type I IFN-induced NET formation and eventually control ox-mtDNA release. Our results demonstrated the important roles of type I IFNs in the pathogenesis of AOSD through their promotion of NET formation, as characterized by the enhanced level of ox-mtDNA. The findings open up new avenues of research into therapeutic approaches for AOSD.
35572553 The NOD Mouse Beyond Autoimmune Diabetes. 2022 Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract Shinogi strain, has represented the gold standard of spontaneous disease models, allowing to investigate autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. Beyond autoimmune diabetes, NOD mice also exhibit polyautoimmunity, presenting with a low incidence of autoimmune thyroiditis and Sjögren's syndrome. Genetic manipulation of the NOD strain has led to the generation of new mouse models facilitating the study of these and other autoimmune pathologies. For instance, following deletion of specific genes or via insertion of resistance alleles at genetic loci, NOD mice can become fully resistant to autoimmune diabetes; yet the newly generated diabetes-resistant NOD strains often show a high incidence of other autoimmune diseases. This suggests that the NOD genetic background is highly autoimmune-prone and that genetic manipulations can shift the autoimmune response from the pancreas to other organs. Overall, multiple NOD variant strains have become invaluable tools for understanding the pathophysiology of and for dissecting the genetic susceptibility of organ-specific autoimmune diseases. An interesting commonality to all autoimmune diseases developing in variant strains of the NOD mice is the presence of autoantibodies. This review will present the NOD mouse as a model for studying autoimmune diseases beyond autoimmune diabetes.
35041110 New-onset Adult-onset Still's disease-like syndrome after ChAdOx1 nCoV-19 vaccination-a ca 2022 May We report a series of 3 Adult-onset Still's disease (AOSD)-like presentations in previously healthy females following vaccination with the ChAdOx1 nCoV-19 vaccine, and also compare them with similar cases reported in literature through a PubMed database search. Our first patient had a high spiking bi-quotidian type of fever with myalgia, sore throat, and arthritis with onset 10-day post-vaccination, with laboratory features of hyper inflammation responding to only naproxen. She was off treatment after 2 months. The second patient, with onset 3-week post-vaccination, had a more severe illness, requiring high dose immunosuppression. In our third case, the onset of illness was slightly delayed i.e., 3-month post-vaccination, but she had the most severe disease with macrophage activation syndrome at presentation requiring immunosuppression and biologicals. The underlying mechanism may be linked to the activation of Toll-like receptors (TLR)-TLR-7 and TLR-9-leading to a robust immune response. These 3 cases highlight the immunogenicity of COVID-19 vaccines, with the possibility of occurrence of new-onset systemic hyper-inflammation illness which can happen a few days following the vaccination, sometimes even delayed to months, and can range in severity from mild to even life-threatening. More cases need to be studied to understand the profile and prognosis of these syndromes in the long run.
35145508 The Role of IgG4 in Autoimmunity and Rheumatic Diseases. 2021 The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren's syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.
35211161 A Final Frontier in Environment-Genome Interactions? Integrated, Multi-Omic Approaches to 2022 Epidemiological and associative research from humans and animals identifies correlations between the environment and health impacts. The environment-health inter-relationship is effected through an individual's underlying genetic variation and mediated by mechanisms that include the changes to gene regulation that are associated with the diversity of phenotypes we exhibit. However, the causal relationships have yet to be established, in part because the associations are reduced to individual interactions and the combinatorial effects are rarely studied. This problem is exacerbated by the fact that our genomes are highly dynamic; they integrate information across multiple levels (from linear sequence, to structural organisation, to temporal variation) each of which is open to and responds to environmental influence. To unravel the complexities of the genomic basis of human disease, and in particular non-communicable diseases that are also influenced by the environment (e.g., obesity, type II diabetes, cancer, multiple sclerosis, some neurodegenerative diseases, inflammatory bowel disease, rheumatoid arthritis) it is imperative that we fully integrate multiple layers of genomic data. Here we review current progress in integrated genomic data analysis, and discuss cases where data integration would lead to significant advances in our ability to predict how the environment may impact on our health. We also outline limitations which should form the basis of future research questions. In so doing, this review will lay the foundations for future research into the impact of the environment on our health.
35061104 The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TS 2022 Jan 22 Metalloproteinases are a group of proteinases that plays a substantial role in extracellular matrix remodeling and its molecular signaling. Among these metalloproteinases, ADAMs (a disintegrin and metalloproteinases) and ADAM-TSs (ADAMs with thrombospondin domains) have emerged as highly efficient contributors mediating proteolytic processing of various signaling molecules. ADAMs are transmembrane metalloenzymes that facilitate the extracellular domain shedding of membrane-anchored proteins, cytokines, growth factors, ligands, and their receptors and therefore modulate their biological functions. ADAM-TSs are secretory, and soluble extracellular proteinases that mediate the cleavage of non-fibrillar extracellular matrix proteins. ADAMs and ADAM-TSs possess pro-domain, metalloproteinase, disintegrin, and cysteine-rich domains in common, but ADAM-TSs have characteristic thrombospondin motifs instead of the transmembrane domain. Most ADAMs and ADAM-TSs are activated by cleavage of pro-domain via pro-protein convertases at their N-terminus, hence directing them to various signaling pathways. In this article, we are discussing not only the structure and regulation of ADAMs and ADAM-TSs, but also the importance of these metalloproteinases in various human pathophysiological conditions like cardiovascular diseases, colorectal cancer, autoinflammatory diseases (sepsis/rheumatoid arthritis), Alzheimer's disease, proliferative retinopathies, and infectious diseases. Therefore, based on the emerging role of ADAMs and ADAM-TSs in various human pathologies, as summarized in this review, these metalloproteases can be considered as critical therapeutic targets and diagnostic biomarkers.
35526972 Peripheral Joint Injections. 2022 May Peripheral joint injections are a common interventional treatment of peripheral joint-mediated pain, including arthritis, tendinopathy, and bursitis that are not responsive to conservative management. Degenerative changes of articular joints are often related to these symptoms through chronic inflammatory changes, which typically arise due to repetitive trauma, autoimmune disease, or metabolic abnormalities. The primary diagnosis for degenerative disease in the peripheral joints is osteoarthritis but can also include rheumatoid arthritis, gout, and other less common etiologies. Chronic inflammatory damage to the articular surfaces and joint capsules can lead to pain and functional decline. As such, the use of peripheral joint injections after the failure of typical conservative treatment, including physical therapy and oral medications, is common. Although these injections are typically not curative in nature, their primary objective is to decrease pain to allow functional improvement concurrently with physical and pharmaceutical modalities. Common injectates used for peripheral joint injections include local anesthetic, corticosteroid, hyaluronic acid, platelet-rich plasma, and mesenchymal stromal cells.
35209781 Evaluating the use of JAK inhibitors in inflammatory connective tissue diseases in pediatr 2022 Mar INTRODUCTION: Connective tissue diseases (CTDs) are a category of conditions that affect tissues that support and provide structure to the body. These diseases include rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, and sclerosing diseases. CTDs can be caused by dysregulation of inflammatory pathways, specifically an upregulation of interferons and JAK/STAT pathway activation. AREAS COVERED: While CTDs have historically been treated with broadly immunosuppressant medications such as corticosteroids and disease-modifying antirheumatic drugs (DMARDS), newer and more targeted immunomodulating medications called Janus kinase inhibitors (JAKi) have emerged as potential treatments. EXPERT OPINION: While most studies regarding JAKi for CTDs have focused on adult populations, pediatric patients with CTDs may also benefit from JAKi therapy. Moreover, the JAK/STAT inhibitor tofacitinib has been approved by the FDA for the treatment of active polyarticular course juvenile idiopathic arthritis. In this review, we have summarized what has been published on the use of JAKi for various pediatric CTDs.
34918137 Complexity of enthesitis and new bone formation in ankylosing spondylitis: current underst 2022 Apr 18 Despite increasing availability of treatments for spondyloarthritis (SpA) including tumour necrosis factor (TNF) and interleukin-17 (IL-17) inhibitors, there is no established treatment that abates new bone formation (NBF) in ankylosing spondylitis (AS), a subset of SpA. Recent research on TNF has revealed the increased level of transmembrane TNF in the joint tissue of SpA patients compared to that of rheumatoid arthritis patients, which appears to facilitate TNF-driven osteo-proliferative changes in AS. In addition, there is considerable interest in the central role of IL-23/IL-17 axis in type 3 immunity and the therapeutic potential of blocking this axis to ameliorate enthesitis and NBF in AS. AS immunopathology involves a variety of immune cells, including both innate and adoptive immune cells, to orchestrate the immune response driving type 3 immunity. In response to external stimuli of inflammatory cytokines, local osteo-chondral progenitor cells activate intra-cellular anabolic molecules and signals involving hedgehog, bone morphogenetic proteins, receptor activator of nuclear factor kappa-B ligand, and Wnt pathways to promote NBF in AS. Here, we provide an overview of the current immunopathology and future directions for the treatment of enthesitis and NBF associated with AS.