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ID PMID Title PublicationDate abstract
33107357 Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotr 2021 Feb BACKGROUND: This study was designed to characterize the interaction between Securidaca inappendiculata Hassk. derived xanthones and methotrexate (MTX). METHODS: Collagen-induced arthritis (CIA) was induced in rats, which were treated with MTX, a xanthone-rich fraction (XRF), or MTX+XRF by gavage for 30 days. Clinical efficacy was assessed based on arthritis scores, serological analysis, and histological examination. Protein expression was investigated by either immunohistochemical or immunoblotting methods. MTX concentrations were determined by HPLC or LC-MS methods. Obtained results were further validated by in vitro assays using 1,7-dihydroxy-3,4-dimethoxyxanthone and HEK 293 T cells. RESULTS: XRF antagonized the antirheumatic effects of MTX in vivo, suggested by higher levels of proinflammatory cytokines, and severer swelling and deformation of joints in CIA rats in the MTX+XRF group compared with MTX monotherapy. XRF reduced MTX concentration in plasma and promoted its excretion into urine. As a result, XRF attenuated MTX-induced edema of the proximal tubule. Furthermore, XRF restored the decreased expression of organic anion transporter three (OAT3), which accounts for MTX secretion in the kidney. Consistently, 1,7-dihydroxy-3,4-dimethoxyxanthone promoted the cellular intake of MTX by increasing OTA3 expression. CONCLUSION: It is suggested that the combined use of S. inappendulata with MTX should be optimized to avoid the antagonistic effects and improve the safety of the MTX regimen.
35379089 Health-related quality of life in patients with rheumatoid arthritis, psoriatic arthritis 2021 Dec 11 OBJECTIVE: Inflammatory joint diseases cause pain and disability. The objective of this study was to measure the quality of life of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with certolizumab pegol and compare the results with those of the  general population. METHOD: Using a cross-sectional design and sociodemographic and clinical  variables, adherence to treatment and quality of life data were collected using  the Euroqol-5d-5L (EQ-5D) questionnaire. The quality of life of the general  population was obtained from the Spanish National Health Survey. Answers to  the EQ-5D questionnaire were analyzed in both groups using two-part models,  which measure the probability of having perfect health as well as the disutility  caused by the disease. RESULTS: The sample included 59 patients with high adherence (92.3%). The  mean utility value was 0.78 and pain was the most affected dimen sion. The  reduction in utility (EQ-5D index) of patients with inflammatory joint disease as  compared to the general population was 0.127. CONCLUSIONS: The subjects of the study showed a significantly lower quality of  life than the general population despite effective control of the disease. Two- part models facilitate the interpretation of quality-of-life studies using the EQ- 5D.
34929227 Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood diso 2022 Feb Most gastrointestinal diseases and disorders (GIDD) are associated with depression, anxiety, and cognitive dysfunction. This suggests that shared features of GIDD, particularly chronic pain and inflammation, affect specific neural targets. The critical review of clinical and animal research presented here reveals that anterior cingulate cortex (ACC) is a primary target. It is particularly sensitive to neuroinflammation, and its function accounts for altered mental function emergent in GIDD. We propose that peripherally-triggered neuroinflammation normally signals injury/illness to ACC, which increases threat assessment and pain sensitivity to cope with increased vulnerability. Chronic peripheral inflammation over-drives this process, leading to long-term ACC structural remodeling, and excessive threat signaling. This evokes anxiodepressive phenotypes even without direct evidence of threats because ACC utilizes schemas to infer affective outcomes (e.g. pain) based on complex contextual information. This activates the autonomic nervous system, exacerbates immune dysfunction, and promotes further gut pathology. This theory provides a mechanistic account of bidirectional interactions among gastrointestinal, immunological, and neural systems in GIDD, and is likely applicable to other chronic inflammatory conditions.
34514936 Birthweight, body size, and growth during childhood and risks of rheumatoid arthritis: a l 2021 Sep 13 Objectives: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA.Method: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930-1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed.Results: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4-9% and 6-10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19-1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA.Conclusions: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.
34809619 Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: 2021 Nov 22 BACKGROUND: Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown. METHODS: We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. RESULTS: The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years. CONCLUSIONS: Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.
34477947 Patient-rated outcome after atlantoaxial (C1-C2) fusion: more than a decade of evaluation 2021 Dec INTRODUCTION: Various surgical techniques have been introduced for atlantoaxial (C1-C2) fusion, the most common being Magerl's (transarticular) or the Harms/Goel screw fixation. Common indications include degenerative osteoarthritis (OA), trauma or rheumatoid arthritis (RA). Only few, small studies have evaluated patient-reported outcomes after C1-C2 fusion. We investigated 2-year outcomes in a large series of consecutive patients undergoing isolated C1-C2 fusion. METHODS: We analysed prospectively collected data (2005-2016) from our Spine outcomes database, collected within the framework of EUROSPINE's Spine Tango Registry. It included 126 patients (34 (27%) men, 92 (73%) women; mean (SD) age 67 ± 19 y) who had undergone first-time isolated C1-C2 fusion (61% Magerl, 39% Harms(-Goel)) at least 2 years ago for OA (83 (66%)), RA (20 (16%)), fracture (15 (12%)) or other (8 (6%)). Patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10) and various single item outcomes. RESULTS: Questionnaires were returned by 118/126 (94%) patients, 2 years post-operative. Mean COMI scores showed a significant reduction from baseline: 6.9 ± 2.4 to 2.7 ± 2.5 (p < 0.0001). Overall, 75% patients achieved the MCIC of ≥ 2.2 points reduction in COMI and 88% reported a good global outcome. 91% patients were satisfied/very satisfied with their care. Self-reported complications were declared by 16% patients and further surgery at the same segment, by 2.5%. CONCLUSION: In this large series with almost complete follow-up, C1-C2 fusion showed extremely good results. Despite the complexity of the intervention, outcomes surpassed those typically reported for simple procedures such as ACDF and lumbar discectomy, suggesting reservations about the procedure should perhaps be reviewed.
34362342 Impact of musculoskeletal disorders on healthy life expectancy in Japan. 2021 Aug 6 BACKGROUND: Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. METHODS: Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. RESULTS: There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0-0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1-0.4) and slightly decreased years with activity limitation (0.1-0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3-1.5 years) and decreased years with activity limitation (0.3-1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0-0.8 years) and non-ADL limitations (0.0-0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7-1.1 years) and non-ADL limitations (0.3-0.4). CONCLUSIONS: These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.
33827262 Advanced oxidation protein products induce inflammatory responses and invasive behaviour i 2021 Apr AIMS: Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. METHODS: We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. RESULTS: AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. CONCLUSION: The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE-NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259-268.
34445238 Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trig 2021 Aug 8 The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.
34310912 Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC 2021 Oct 5 Epidemiological data suggest that the incidence of rheumatoid arthritis (RA) increases in postmenopausal women, which may be related to estrogen deficiency. Tissue acidosis is a common symptom of RA. Acid-sensitive ion channel 1a (ASIC1a), a member of the extracellular H(+)-activated cation channel family, could be activated by changes in extracellular pH and plays a crucial role in the pathogenesis of RA. As the only cellular component in cartilage tissue, chondrocytes play an extremely important role in maintaining cartilage tissue homeostasis. The aim of this study was to investigate whether estrogen could protect acid-stimulated chondrocytes by regulating the expression of ASIC1a and explore the possible mechanism. The results showed that estrogen could protect against acid-induced chondrocyte injury by reducing ASIC1a protein expression. Moreover, lysosome inhibitor chloroquine (CQ) and autophagy inhibitor 3-methyladeniine (3-MA) could reverse the reduction of ASIC1a protein caused by estrogen, indicating that autophagy-lysosome pathway contributes to estrogen-induced degradation of ASIC1a protein. Furthermore, the down-regulation of ASIC1a expression by estrogen was attenuated by MPP, a specific inhibitor of estrogen-related receptor-alpha (Esrra), indicating that Esrra is involved in the process of estrogen regulating the expression of ASIC1a. Additionally, adenosine 5'-monophosphate (AMP)-activated protein kinase/unc-51-like kinase 1 (AMPK-ULK1) signaling pathway was activated by estrogen treatment, which was abrogated by Esrra-silencing, and AMPK-specific inhibitor Compound C pretreatment could reduce estrogen-induced downregulation of ASIC1a protein. Taken together, these results indicate that estrogen could promote autophagy-lysosome pathway-dependent ASIC1a protein degradation and protect against acidosis-induced cytotoxicity, the mechanisms of which might relate to Esrra-AMPK-ULK1 signaling pathway.
34131623 Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical rem 2021 OBJECTIVES: Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender vs mainly swollen joints had differences in patient-reported outcome measures (PROMs), clinical or US assessments or in achieving remission defined by CDAS or US. METHODS: In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and US assessments (36 joints and 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to clinical disease activity index (CDAI)/Boolean or no Doppler activity present. Tender-swollen joint differences (TSJDs) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann-Whitney, Kruskal-Wallis and Spearman tests. RESULTS: One hundred and ten patients were included [mean (s.d.) age 55.6 (12.1) years, RA duration 8.7 (9.5) years]. All PROMs, clinical, laboratory and US scores decreased during follow-up (P < 0.001). During follow-up, tender joint counts were correlated primarily with PROMs [r = 0.24-0.56 (P < 0.05-0.001)] and swollen joint counts with US synovitis scores [r = 0.33-0.72 (P < 0.05-0.001)]. At 24 weeks, patients with TSJD > 0 had higher PROMs and CDAI (P < 0.05-0.001) but lower US synovitis scores (P < 0.05). Remission by CDAI/Boolean was seen in 26-34% and by Doppler 53%, but only 2-3% of patients with TSJD > 0 achieved CDAI/Boolean remission. CONCLUSION: Patients with more tender than swollen joints scored higher on subjective assessments but had less US synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02046616.
33609724 Sinomenine-phenolic acid coamorphous drug systems: Solubilization, sustained release, and 2021 Apr 1 Sinomenine (SIN), isolated from Caulis sinomenii, is a benzyltetrahydroisoquinoline-type alkaloid with potent anti-inflammatory and analgesic effects. SIN-HCl has been used in the forms of tablets or enteric-coated tablets in the treatment of rheumatoid arthritis in China for years, while its short half-life leads to attenuated therapeutic effects and serious side effects. In the current study, three phenolic acids, including salicylic acid (SAA), 2,3-dihydroxybenzoic acid (23DHB), and 2,4-dihydroxybenzoic acid (24DHB), were firstly employed as coamorphous coformers to prepare three binary SIN-phenolic acid coamorphous systems. These new coamorphous systems were characterized by powder X-ray diffraction (PXRD), modulated temperature differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The formation of SIN-phenolic acid coamorphous systems are supported by the absence of diffraction peaks in their PXRD spectra, as well as the single T(g)s of three samples (i.e., SIN-SAA, SIN-23DHB, and SIN-24DHB) at 109.5 °C, 124.9 °C, and 135.3 °C. Importantly, the salt formation between SIN and phenolic acids was observed in FTIR. In three coamorphous systems, coamorphous SIN-24DHB shows superior physicochemical stability under both low humidity and accelerated storage conditions. They were also more soluble than crystalline SIN, while were released slower than the commercial SIN-HCl in dissolution experiments. Therefore, our study suggests that phenolic acids may be used as a new type of coformers in the preparation of coamorphous systems for active pharmaceutical ingredients.
34537268 (177)Lu-labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent. 2021 Oct 25 Micro-sized multivesicular liposomes were prepared, radiolabeled with (177)Lu, and tested in vitro and in vivo to evaluate the potential of (177)Lu-labeled micro liposomes in radiosynoviorthesis (RSO) therapy. A standard reverse-phase procedure of liposome preparation with a lipid mixture of DPPC: CHOL (80:20%) was used for the synthesis. TEM and fluorescence microscopy imaging were performed to determine the size, shape, and structure of the prepared liposomes. Both measurements are in good agreement while TEM micrographs additionally indicate to a large multivesicular inner structure of prepared liposomes. A simple and straightforward procedure was used for liposome radiolabeling with (177)Lu, a well-known and commonly used radionuclide in radiotherapy with favorable properties, that can be exploited in RSO therapy. Radiolabeled (177)Lu-liposomes were tested in vitro for stability and then injected into the knee joints of Wistar rats where liposome in vivo behavior was followed up to 30 days post injection. Results from both ex vivo biodistribution and in vivo imaging studies presented a high stability and retention (>94 %ID) of (177)Lu-micro liposomes in the synovial liquid for the entire observation period. Leakage of free (177)Lu or (177)Lu-liposomes from the synovial fluid has not been detected, indicating to a possible application of (177)Lu-liposomes in radiosynoviorthesis (RSO) therapy.
34085304 Melatonin effects on bone: Implications for use as a therapy for managing bone loss. 2021 Aug Melatonin is the primary circadian output signal from the brain and is mainly synthesized in pinealocytes. The rhythm and secretion of melatonin are under the control of an endogenous oscillator located in the SCN or the master biological clock. Disruptions in circadian rhythms by shift work, aging, or light at night are associated with bone loss and increased fracture risk. Restoration of nocturnal melatonin peaks to normal levels or therapeutic levels through timed melatonin supplementation has been demonstrated to provide bone-protective actions in various models. Melatonin is a unique molecule with diverse molecular actions targeting melatonin receptors located on the plasma membrane or mitochondria or acting independently of receptors through its actions as an antioxidant or free radical scavenger to stimulate osteoblastogenesis, inhibit osteoclastogenesis, and improve bone density. Its additional actions on entraining circadian rhythms and improving quality of life in an aging population coupled with its safety profile make it an ideal therapeutic candidate for protecting against bone loss in susceptible populations. The intent of this review is to provide a focused discussion on bone loss and disorders of the bone as it relates to melatonin and conditions that modify melatonin levels with the hope that future therapies include those that include melatonin and correct those factors that modify melatonin levels like circadian disruption.
34522257 Management of rheumatoid arthritis in Poland - where daily practice might not always meet 2021 INTRODUCTION: International recommendations are intended to help rheumatologists in the effective management of rheumatoid arthritis (RA) through an evidence-based approach. This research aimed to evaluate management patterns and associated difficulties encountered by rheumatologists in daily practice. MATERIAL AND METHODS: Interviewers recruited 101 Polish rheumatologists in a random quota-based, nationwide sample of outpatient clinics. Quantitative data were input online using a computer-assisted web interview tool. RESULTS: Disease-modifying antirheumatic drugs (DMARDs) are not initiated at the time of diagnosis in 15% of RA patients, most often due to difficulties in patient-provider communication. The RA activity is assessed every 4 to 6 months by 30% of rheumatologists, and 64% of patients are reported to never achieve remission. Composite indices are the most reliable indicators of remission only for 38% of responders. Despite inadequate disease control with ≥ 2 treatment schedules with synthetic DMARDs, 34% of these patients are not considered for biological DMARDs (bDMARDs). Contraindications and reimbursement barriers are the most frequently stated reasons. Therapy with glucocorticoid (GC) lasting over 3 months is reported by 70% of rheumatologists. International recommendations are stated as the most common basis for treatment decisions. CONCLUSIONS: Awareness of recommendations is not sufficient to ensure their application in clinical practice. Inadequate management of RA is quite prevalent, with a substantial contribution of non-medical factors. Daily practice mainly deviates from guidelines regarding frequency and mode of monitoring measures, time to DMARD initiation, and duration of GC treatment. Education programs and policy changes may significantly narrow the gap between evidence and practice.
33866600 A review of signaling and transcriptional control in T follicular helper cell differentiat 2022 Jan T follicular helper (Tfh) cells are a critical component of adaptive immunity and assist in optimal Ab-mediated defense. Multiple effector functions of Tfh support germinal center B cell survival, Ab class switching, and plasma cell maturation. In the past 2 decades, the phenotype and functional characteristics of GC Tfh have been clarified allowing for robust studies of the Th subset including activation signals and environmental cues controlling Tfh differentiation and migration during an immune response. A unique, 2-step differentiation process of Tfh has been proposed but the mechanisms underlying transition between unstable Tfh precursors and functional mature Tfh remain elusive. Likewise, newly identified transcriptional regulators of Tfh development have not yet been incorporated into our understanding of how these cells might function in disease. Here, we review the signals and downstream transcription factors that shape Tfh differentiation including what is known about the epigenetic processes that maintain Tfh identity. It is proposed that further evaluation of the stepwise differentiation pattern of Tfh will yield greater insights into how these cells become dysregulated in autoimmunity.
33211944 Retro-Odontoid Pseudotumor Formation in the Context of Various Acquired and Congenital Pat 2021 Mar Retro-odontoid pseudotumor formation consists of an abnormal growth of granulation tissue typically posterior to the odontoid process, resulting as a manifestation of atlantoaxial instability. This instability can occur as a result of conditions ranging from severe mechanical trauma to metabolic disease or autoimmune conditions such as rheumatoid arthritis. A pseudotumor may impinge on the spinal nerves or even the spinal cord and brainstem, manifesting symptoms from severe neck pain to cervicomedullary compression or myelopathy, and in some cases even sudden death. The objective of this review is to consolidate the findings in published case reports and relevant prior literature reviews regarding the formation of retro-odontoid pseudotumor. We address the pathophysiology involved in acquired and congenital pseudotumor formation, including those associated with rheumatoid arthritis (panni). Additionally, we discuss past and current operative techniques designed to curtail and ultimately regress a retro-odontoid pseudotumor and pannus. Surgical techniques that are addressed include ventral decompression (both transoral and transnasal), dorsal decompression, and indications for posterior instrumentation in pannus formation, particularly in cases that may be sufficiently treated in lieu of an anterior approach. Finally, we will examine the role of external orthoses as both a method of conservative treatment as well as a potential adjunct to the aforementioned surgical procedures.
33159795 Interferon-stimulated GTPases in autoimmune and inflammatory diseases: promising role for 2021 Feb 1 Human IFNs are secreted cytokines shown to stimulate the expression of over one thousand genes. These IFN-inducible genes primarily encode four major protein families, known as IFN-stimulated GTPases (ISGs), namely myxovirus-resistance proteins, guanylate-binding proteins (GBPs), p47 immunity-related GTPases and very large inducible guanosine triphosphate hydrolases (GTPases). These families respond specifically to type I or II IFNs and are well reported in coordinating immunity against some well known as well as newly discovered viral, bacterial and parasitic infections. A growing body of evidence highlights the potential contributory and regulatory roles of ISGs in dysregulated inflammation and autoimmune diseases. Our focus was to draw attention to studies that demonstrate increased expression of ISGs in the serum and affected tissues of patients with RA, SS, lupus, IBD and psoriasis. In this review, we analysed emerging literature describing the potential roles of ISGs, particularly the GBP family, in the context of autoimmunity. We also highlighted the promise and implications for therapeutically targeting IFNs and GBPs in the treatment of rheumatic diseases.
34605934 Lung fibrosis in autoimmune diseases and hypersensitivity: how to separate these from idio 2021 Oct 4 Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered.
34434435 Hepatic Hodgkin Lymphoma Presenting as Solitary Hepatic Mass Following Other Iatrogenic Im 2021 Feb Lymphoproliferative disorders (LPDs) occur frequently in patients with rheumatoid arthritis (RA) under methotrexate treatment. Some LPDs spontaneously regressed after methotrexate discontinuation, but classic Hodgkin lymphoma (CHL)-type LPDs frequently relapse, and chemotherapy is usually required for the treatment. CHL usually spreads in contiguous lymph nodes and then infiltrates in organs at an advanced stage. Thus, hepatic Hodgkin lymphoma (HHL) without lymphadenopathy is extremely rare at diagnosis. We present a case of methotrexate-associated LPDs associated with systemic lymphadenopathy and hepatosplenic mass in a 71-year-old woman with RA under methotrexate treatment over 10 years. Although spontaneous remission occurred after methotrexate discontinuation, she developed HHL presenting as a solitary hepatic mass without lymphadenopathy 3 years after spontaneous regression. She received brentuximab vedotin (BV) combination chemotherapy without bleomycin to avoid pulmonary toxicity. Complete metabolic response was achieved after four courses of BV combination chemotherapy, and the activity of RA was kept to be in remission. Our case suggested that the recurrence lesions of LPDs may present at unexpected site, which is not coincide with the primary site, and BV combination chemotherapy is a promising regimen for limited-stage CHL-type LPDs in patients with RA owing to its anti-lymphoma effect on CHL-type LPDs and a possible targeted therapy for RA.