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ID PMID Title PublicationDate abstract
34758517 Identification and Prediction of Fatigue Trajectories in People With Rheumatoid Arthritis. 2022 Feb OBJECTIVE: We aimed to identify groups demonstrating different long-term trajectories of fatigue among people with rheumatoid arthritis and determine baseline predictors for these trajectories. METHODS: Our study included 2741 people aged 18 to 75 years who were independent in daily living. Data were collected from the Swedish Rheumatology Quality Register and questionnaires at baseline, 14 months, and 26 months. Fatigue was rated on a 100-mm visual analog scale. K-means cluster analysis was used to identify fatigue trajectories. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for potential predictors of trajectory membership. RESULTS: The mean age was 60 years, 73% of participants were female, and the mean baseline fatigue level was 39. Three distinct fatigue trajectories were identified, representing mild (mean 15, n = 1024), moderate (mean 41, n = 986), and severe (mean 71, n = 731) fatigue. Consistent patterns indicated that poorer health perception (ORs 1.68-18.40), more pain (ORs 1.38-5.04), anxiety/depression (ORs 0.85-6.19), and activity limitation (ORs 1.43-7.39) were associated with more severe fatigue. Those in the severe fatigue group, compared with those in the mild fatigue group, were more likely to be college educated than university educated (OR 1.56) and less likely to maintain physical activity (OR 0.54). Those in the severe fatigue group, compared with those in both the moderate (OR 0.67) and mild (OR 0.59) fatigue groups, were less likely to have one additional adult in the household. CONCLUSION: This study identified stable fatigue trajectories, predicted by health perception, pain, anxiety/depression, activity limitation, educational level, maintained physical activity, and household composition. Interventions aimed at reducing these disabilities and supporting physical activity behaviors may help reduce fatigue.
35249157 Two flares of Still's disease after two doses of the ChAdOx1 vaccine. 2022 May We report the case of an 18-year-old male with Still's disease for the last 3 years, in remission, who developed two flares of his disease after receiving two doses of the ChAdOX1 nCoV-19 vaccine. While the first flare was mild requiring steroid initiation and resolved rapidly, the second flare after the second dose was much severe, requiring pulse steroid and tocilizumab. We also review three reported cases of flares of Still's disease after COVID-19 vaccination. The temporal association of the flares with both vaccine doses strengthens the association between the vaccine administration and the flare. The proposed mechanism may be due to activation of the innate immune system by the vaccine adjuvants. This review serves to inform the medical community regarding a possible role of the vaccine in producing a systemic inflammatory response. Early detection and treatment can help reduce morbidity in these cases.
35358679 Toll-like receptor 10 expression in B cells is negatively correlated with the progression 2022 Apr Primary Sjögren's Disease (pSjD) is considered a B cell-mediated disease. Toll-like receptor 10 (TLR10) is highly expressed in human B cells, indicating that TLR10 probably plays a vital role in pSjD. We examined TLR10 expression in peripheral B subsets of pSjD patients and analyzed their association with disease activity. We observed that TLR10 expression in total, naïve, memory, and switched memory B cells was significantly increased in low-activity pSjD patients as compared with healthy controls and high-activity patients. TLR10 expression in the above mentioned B subsets (except naïve B) was negatively correlated with serum levels of anti-SSA antibody and BAFF, respectively. Moreover, a higher proportion of high-activity pSjD patients was observed in TLR10 low- than high-expressed patients. Our study concluded that TLR10 expression in CD19(+) B and memory B was negatively correlated with pSjD disease activity, suggesting that TLR10 might take part in the progression of pSjD.
35159133 Saliva Metabolomics in Dry Mouth Patients with Head and Neck Cancer or Sjögren's Syndrome 2022 Jan 19 The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren's syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes behind dry mouth with different etiologies, we investigated the metabolic profile of 10 HNC patients, 9 pSS patients and 10 healthy controls using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) metabolomics. Principal component analysis (PCA) revealed different metabolic profiles when comparing all subjects included in the study. Both patient groups showed higher ratios of several pyrimidine nucleotides and nucleosides when compared to controls. This finding may indicate that purinergic signaling plays a role in dry mouth conditions. Moreover, significantly increased levels of DL-3-aminoisobutyric acid were found in HNC patients when compared to controls, and a similar tendency was observed in the pSS patients. Furthermore, a dysregulation in amino acid metabolism was observed in both patient groups. In conclusion, metabolomics analysis showed separate metabolic profiles for HNC and pSS patients as compared to controls that could be useful in diagnostics and for elucidating the different pathophysiologies. The demonstrated dysregulation of pyrimidine nucleotides and levels of metabolites derived from amino acids in the patient groups should be studied further.
35370946 Case Report: Onset of Type 1 Diabetes Mellitus in a Patient With Ulcerative Colitis and Sj 2022 Type 1 diabetes mellitus (T1DM) is often complicated with some other autoimmune disorders. The complication of various autoimmune disorders is known as autoimmune polyglandular syndrome (APS). Once autoimmune thyroid disease develops, various autoimmune diseases can also occur. Such phenomena are classified as APS types 3A to 3D. In this report, we show the onset of T1DM in a patient with ulcerative colitis (UC) and Sjogren's syndrome. The most important and interesting point in this case is that, if we did not check her thyroid-associated antibodies, we could not have diagnosed her as APS. From the data of this case, we assumed that the patient suffered from APS type 3A, 3B, and 3D variants. This case pointed out very clearly the importance of testing for thyroid-associated antibodies under various autoimmune disease conditions even if the thyroid hormone levels are euthyroid. Moreover, based on the strong linkage between inflammatory bowel disease and T1DM and the compatibility with both T1DM and APS type 3, we think it is possible that Hashimoto's disease is present under complicated conditions together with UC and T1DM. It would be important to repeatedly check for thyroid-associated antibodies even in euthyroid patients, especially under various autoimmune disease conditions.
34654730 Long-term Safety of Rituximab in Primary Sjögren Syndrome: The Experience of a Single Cen 2022 Feb OBJECTIVE: This work aims to evaluate the long-term safety of rituximab (RTX) in primary Sjögren syndrome (pSS) and to determine the safety and the efficacy of long-term treatment with B cell depleting therapy in pSS patients with active systemic disease. METHODS: A historical cohort study, enrolling 35 patients with pSS treated with RTX between 2008 and 2019 in a single rheumatologic unit, was performed. When patients experienced adverse events, the treatment was suspended and patients' data were recorded. RESULTS: The included patients were mainly female (91%), with a mean age of 54 years. During the time of observation, 13 patients (37.1%) suspended RTX treatment (10 cases per 100 patient-years, 95% CI 0.06-0.17). Baseline demographics, disease characteristics, European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) values, and treatment were comparable across RTX-suspended and nonsuspended groups. Patients exposed to RTX had been followed for 35.82 ± 32.56 months, and the time of observation varied from 6 to 96 months. All the patients except one experienced a significant and persisting meaningful improvement of their ESSDAI (≥ 3 points) during the long-term follow-up. For the duration of the follow-up, 13 (37%) patients discontinued RTX treatment. Four out of 13 (30.8%) discontinued the treatment after the first administration due to infusion-related reactions. During subsequent RTX courses, the main cause of withdrawal was hypogammaglobulinemia onset (7 patients). In 2 patients, hypogammaglobulinemia was associated with severe infections. CONCLUSION: Long-term RTX administration was shown to be a safe, well tolerated, and effective treatment in patients with active systemic disease, significantly reducing ESSDAI and controlling disease activity.
34748286 Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren's Syndrome 2022 Apr OBJECTIVE: Salivary gland epithelial cells (SGECs) are key cellular drivers in the pathogenesis of primary Sjögren's syndrome (SS); however, the mechanisms sustaining SGEC activation in primary SS remain unclear. We undertook this study to determine the role of autophagy in the survival and activation of SGECs in primary SS. METHODS: Primary SGECs isolated from the minor SGs of patients with primary SS or sicca syndrome were evaluated by flow cytometry, immunoblotting, and immunofluorescence to assess autophagy (autophagic flux, light chain 3 IIB [LC3-IIB], p62, LC3-IIB+/lysosome-associated membrane protein 1 [LAMP-1] staining), apoptosis (annexin V/propidium iodide [PI], caspase 3), and activation (intercellular adhesion molecule, vascular cell adhesion molecule). Focus score and germinal center presence were assessed in the SGs from the same patients to assess correlation with histologic severity. Human SG (HSG) cells were stimulated in vitro with peripheral blood mononuclear cells (PBMCs) and serum from primary SS patients in the presence or absence of autophagy inhibitors to determine changes in autophagy and epithelial cell activation. RESULTS: SGECs from primary SS patients (n = 24) exhibited increased autophagy (autophagic flux [P = 0.001]; LC3-IIB [P = 0.02]; p62 [P = 0.064]; and as indicated by LC3-IIB/LAMP-1+ staining), increased expression of antiapoptotic molecules (Bcl-2 [P = 0.006]), and reduced apoptosis (annexin V/PI [P = 0.002]; caspase 3 [P = 0.057]), compared to samples from patients with sicca syndrome (n = 16). Autophagy correlated with histologic disease severity. In vitro experiments on HSG cells stimulated with serum and PBMCs from primary SS patients confirmed activation of autophagy and expression of adhesion molecules, which was reverted upon pharmacologic inhibition of autophagy. CONCLUSION: In primary SS SGECs, inflammation induces autophagy and prosurvival mechanisms, which promote SGEC activation and mirror histologic severity. These findings indicate that autophagy is a central contributor to the pathogenesis of primary SS and a new therapeutic target.
34471033 Nodular Pulmonary Amyloidosis Associated with Sjögren's Syndrome. 2022 Mar 15 Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.
35614481 The effects of custom-made foot orthoses on foot pain, foot function, gait function, and f 2022 May 25 INTRODUCTION: Foot involvement is a significant concern in psoriatic arthritis (PsA) as it can lead to severe levels of foot pain and disability and reduced mobility and quality of life. Previous studies have shown moderate efficacy for custom-made foot orthoses (CFO) in reducing foot pain and disability in people with rheumatoid arthritis. However, evidence on the efficacy of CFO in people with PsA is lacking. OBJECTIVES: To explore the effects of CFO on foot function, foot and lower limb pain, gait function, and free-living walking activities (FWA) in people with PsA. METHODS: A pre-experimental study including twenty participants with PsA (mean age: 54.10 ± 9.06 years and disease duration: 11.53 ± 10.22 years) was carried out. All the participants received and wore CFO for 7 weeks. Foot and lower limb pain and foot function were measured before and after the intervention using the numerical rating scale (NRS) and the foot function index (FFI). Gait function was assessed by recording spatiotemporal parameters (STPs) during a 10-m walk test using an instrumented gait analysis system (Mobility Lab). Free-living walking activities (step count, free-living cadence, time spent in different ambulatory physical activities (APA)) were recorded over 7 days using an accelerometer-instrumented sock. RESULTS: The FFI reported scores demonstrated severe baseline levels of foot pain (54.46 ± 14.58 %) and disability (46.65 ± 16.14%). Statistically and clinically significant improvements in foot pain and foot function and large effect sizes (Cohen's effect size > 1, p < 0.005) were observed after the intervention period. A strong correlation (r = -0.64, p < 0.01) between the CFO wearing time and foot function was demonstrated. However, no significant changes were found for gait STP or free-living walking activities after 7 weeks of CFO use. CONCLUSION: Results support the clinical and biomechanical plausibility of using CFO in people with PsA to reduce pain and improve foot function. Large-scale and controlled studies are needed to confirm these findings. Moreover, a multidisciplinary approach including the prescription of exercise therapy and physiotherapy combined with CFO could be required to improve STP and promote APA in people with PsA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05075343 . Retrospectively registered on September 29, 2021.
32772578 Nonunion and Reoperation Following Proximal Interphalangeal Joint Arthrodesis and Associat 2022 May BACKGROUND: Proximal interphalangeal joint (PIPJ) arthrodesis can provide reliable pain relief and restore hand function in patients with PIPJ arthritis. However, there is a paucity of literature on patient-specific preoperative risk factors that are associated with adverse outcomes after PIPJ arthrodeses. Therefore, the primary purpose of this study was to assess preoperative predictors of nonunion and reoperation after PIPJ arthrodesis. METHODS: This study identified all patients who underwent PIPJ arthrodesis at a single community practice between 1987 and 2013. The final analysis included 415 PIPJs treated with arthrodesis. The mean follow-up was 1.3 years. Data on preoperative diagnosis, demographics, comorbidities, and operative techniques were recorded, as well as the occurrence of nonunions and reoperations. Logistic regression models were used to identify independent risk factors of nonunion and reoperation. RESULTS: There were 40 nonunions (10%) and 62 reoperations (15%). Of the reoperations, there were 39 incidences of isolated hardware removal, 9 irrigation and debridement, 8 amputations, 5 revision arthrodeses, and 1 corrective osteotomy. The highest number of nonunions occurred in the traumatic diagnosis group (37%), followed by the rheumatoid group (23%) and the scleroderma group (15%). The highest number of reoperations occurred within the traumatic joint disorder group (40%), followed by the rheumatoid group (24%) and the scleroderma group (11%). Multivariate analysis revealed that male sex (P < .01) and hepatic disease (P = .03) were significant risk factors of nonunion. Male sex was also significantly associated with increased reoperation risk (P < .01). CONCLUSION: Risks of nonunions and reoperations after PIPJ arthrodeses are low; however, these findings may guide clinicians and patients in the preoperative decision-making process and help with targeted postoperative surveillance to mitigate these risks.
35145770 Relapse and Outcome of Lupus Nephritis After Renal Transplantation in the Modern Immunosup 2022 Jan Background Recurrence of lupus nephritis in the graft is a concern in lupus patients with end-stage renal disease undergoing renal transplantation. The recurrence of lupus nephritis has been variable among different studies depending on the patient characteristics, immunosuppressive regimen, and indications of renal biopsy. Therefore, we investigated the recurrence of lupus nephritis among our patients to see if the new post-transplant regimen has impacted the recurrence. Methods We collected data on all recipients with end-stage renal disease secondary to lupus nephritis, who received renal transplants between 2006-2017 in our center. Patient demographics, transplant, and dialysis-related information have been recorded including kidney biopsy, graft loss, and survival were recorded. An association between recurrent lupus nephritis with survival and/or graft loss was examined using survival models. Results The overall mean±SD age at baseline was 42±13 years; 89% were female; 89% were African American; the previous time on dialysis was a median of 4 years (IQR: 2-8 years), 81% received hemodialysis and 31% received living donor transplantation in the cohort. Our patients received the standard immunosuppressive regimen consisting of prednisone, tacrolimus, and mycophenolate mofetil. Four (10.5%) of the 38 patients had biopsy-proven lupus nephritis recurrence. A total of 10 patients (26%) had graft loss or died during the median follow-up time of 1,230 days (IQR: 460-2,227 days). Recurrence of lupus nephritis showed a trend for increased risk of graft loss or patient death (Hazard Ratio: 3.14, 95%Confidence Interval: 0.65-15.24) compared to the recipient without recurrence in our unadjusted proportional Cox regression model. Conclusion The recurrence rate of lupus nephritis in our patient population is much lower compared to past studies from different immunosuppressive eras. Patients with recurrent lupus nephritis showed an increased risk of graft loss or death.
34398520 Activation of Hypothalamic AMP-Activated Protein Kinase Ameliorates Metabolic Complication 2022 Feb OBJECTIVE: To investigate whether thermogenesis and the hypothalamus may be involved in the physiopathology of experimental arthritis (EA). METHODS: EA was induced in male Lewis rats by intradermal injection of Freund's complete adjuvant (CFA). Food intake, body weight, plasma cytokines, thermographic analysis, gene and protein expression of thermogenic markers in brown adipose tissue (BAT) and white adipose tissue (WAT), and hypothalamic AMP-activated protein kinase (AMPK) were analyzed. Virogenetic activation of hypothalamic AMPK was performed. RESULTS: We first demonstrated that EA was associated with increased BAT thermogenesis and browning of subcutaneous WAT leading to elevated energy expenditure. Moreover, rats experiencing EA showed inhibition of hypothalamic AMPK, a canonical energy sensor modulating energy homeostasis at the central level. Notably, specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus (a key site modulating energy metabolism) reversed the effect of EA on energy balance, brown fat, and browning, as well as promoting amelioration of synovial inflammation in experimental arthritis. CONCLUSION: Overall, these data indicate that EA promotes a central catabolic state that can be targeted and reversed by the activation of hypothalamic AMPK. This might provide new therapeutic alternatives to treat rheumatoid arthritis (RA)-associated metabolic comorbidities, improving the overall prognosis in patients with RA.
34996072 Autoantibodies in Psoriatic Disease. 2022 Jan 5 BACKGROUND: Psoriasis (Ps) is an inflammatory skin disease affecting over 8 million people in the USA and Canada. Approximately a quarter of patients with Ps have an inflammatory arthritis termed psoriatic arthritis (PsA). Psoriatic disease encompassing both Ps and PsA is regarded as an immune-mediated inflammatory disease, exhibiting both autoimmune and autoinflammatory features. Innate immune cell activation promotes inflammation and the cellular infiltrate in inflamed tissue is predominantly lymphocytic. CONTENT: A narrative review of the current literature on the presence and clinical significance of autoantibodies found in psoriatic disease are presented. The frequency of several autoantibodies in Ps and PsA patients as well as their association with disease diagnosis, disease activity, and treatment response are reviewed. SUMMARY: Despite historically described as a rheumatoid factor negative (seronegative) disease, an array of autoantibodies has been identified in patients with psoriatic disease. Many of the autoantibodies reviewed are elevated in Ps and PsA patients and are associated with disease activity, treatment response, and cardiovascular disease risk. The identification of autoantibodies in Ps and PsA patients points to an autoimmune component potentially playing a role in psoriatic disease; however, additional evidence is needed to determine the clinical utility of these autoantibodies and their contribution to disease pathogenesis.
35297492 Drug Treatment Algorithm and Recommendations from the 2020 update of the Japan College of 2022 Mar 16 OBJECTIVE: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) (JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members. RESULTS: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-RANKL antibodies, and JAK inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach. CONCLUSION: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision making in a variety of clinical situations.
35243298 Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis 2022 Mar Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.
35435319 Efficacy and safety of tofacitinib in the treatment of refractory cases of polyarticular c 2022 Apr 18 BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) are treatment options for refractory juvenile idiopathic arthritis (JIA) cases which cannot be afforded by the majority. Tofacitinib is a novel Janus kinase inhibitor, which is reported to be a cost-effective oral alternative to biologics. This prospective observational study was carried out to observe the efficacy and safety of tofacitinib in refractory polyarticular course JIA patients. MATERIALS AND METHODS: The study was conducted in the Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Twenty-seven refractory polyarticular course JIA patients were included in this study. Patients received tofacitinib at recommended doses. Disease activity level was assessed by Juvenile Arthritis Disease Activity Score (JADAS) 27. Cases were evaluated at baseline and at the 6th, 12th and 24th weeks. Safety was monitored from history, examination findings and laboratory reports. Data were analyzed using appropriate statistical tests. RESULTS: Enthesitis-related arthritis was the commonest type (37%) followed by polyarticular (rheumatoid factor+) and systemic JIA. There was significant improvement in JADAS 27 in all the subtypes of JIA except oligoarticular extended type. Among 100% high disease activity state cases at baseline, 70.4% were inactive at 24 weeks. It was also possible to significantly reduce the dose of steroid. Few side effects like headache and vomiting, elevation of alanine aminotransferase and anemia were observed at 6 weeks. These side effects subsequently improved. CONCLUSION: Significant reduction of disease activity score was observed from baseline to follow up in this study. Tofacitinib was well tolerated with minimum side effects.
35327525 Production and Secretion of Gelsolin by Both Human Macrophage- and Fibroblast-like Synovio 2022 Mar 21 Gelsolin (GSN) is an actin-binding protein involved in cell formation, metabolism and wound closure processes. Since this protein is known to play a role in arthritis, here we investigate how the synovial membrane with its specific synoviocytes contributes to the expression of GSN and how the amount of GSN expressed is modulated by different types of arthritis. Synovial membranes from adult healthy subjects and patients with rheumatoid arthritis (RA) and osteoarthritis (OA) are analyzed by immunofluorescence, Western blot and ELISA. Macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) were isolated, cultured and analyzed for their potential to produce and secrete GSN. In addition, the GSN concentrations in the synovial fluid of various forms of arthritis are determined by ELISA. GSN is produced by the healthy and arthritic synovial membranes. Both forms of synoviocytes (MLS and FLS) release GSN. The results show that there is a significant reduction in GSN in the synovial fluid in adult patients with OA. This reduction is also detectable in adult patients with RA but is not as evident. In juvenile arthritis, there is a slight increase in GSN concentration in the synovial fluid. This study shows that primary MLS and FLS express GSN and that these cells, in addition to articular chondrocytes, contribute to GSN levels in synovial fluid. Furthermore, GSN concentrations are modulated in different types of arthritis. Further studies are needed to fully understand how GSN is involved in joint homeostasis.
35579083 Lack of cross-reactivity between rheumatoid factor IgM and anti-S1 receptor binding domain 2022 Apr 29 OBJECTIVES: Since the onset of the COVID-19 outbreak, concern has been raised about reliability of SARS-CoV-2 serological tests in people with serum positivity for rheumatoid factor (RF), due to its ability to interfere during tests carried out with immunoassay techniques, leading to false positive results. The aim of this study was to analyse, on sera from RF seropositive rheumatoid arthritis (RA) patients, the interference between RF IgM and anti-S1 RBD IgM. METHODS: The study was conducted on consecutive patients affected by RF seropositive RA and, as control group, COVID-19 patients with SARS-CoV-2 pneumonia hospitalised at Sapienza University of Rome from April 2020 and April 2021. Serum samples from COVID-19 patients during their hospitalisation were collected, while RA subjects' samples were harvested prior to the onset of the COVID-19 pandemic. All samples were tested for RF IgM using nephelometry and ELIA, and for anti-S1 RBD IgM by ELISA. RESULTS: Forty RF seropositive RA and 42 COVID-19 patients were enrolled. In all RA patients, both nephelometric assay and ELIA showed RF IgM positivity, while only one patient of the control group tested positive for RF IgM by nephelometric assay and ELIA. IgM directed to S1 RBD were not detected in sera of RA patients, while all COVID-19 patients presented anti-S1 RBD IgM (median anti-S1 RBD IgM COVID-19 vs. RA: 368.5 IU/mL, IQR 654 IU/mL vs. 18.45 IU/mL, IQR 20 IU/mL; p<0.0001). CONCLUSIONS: This study confirmed the lack of cross-reactivity between RF and anti-S1 RBD IgM, offering to clinicians a valuable tool for a better management of RA patients undergoing SARSCoV-2 serological tests.
33861386 In vitro effects of curcumin on proinflammatory cytokines and expression of their genes in 2022 Mar Curcumin reduces disease severity and ameliorates lupus-like/Sjögren's Syndrome-like disease in mice model. The immunological basis of these effects is largely unknown. This study examined the effects of curcumin on pro-inflammatory cytokines secreted by minor salivary glands in patients with primary Sjögren's syndrome (pSS). Minor salivary gland (MSG) tissue samples were collected from patients undergoing biopsy for suspected pSS. The tissues were treated with phytohemagglutinin (PHA) alone as well as PHA with curcumin (30 μM) and cultured in RPMI 1640 medium for 48 h at 37 °C in CO(2) incubator. After the incubation period, culture supernatant and tissues were stored in the freezer (-80 °C). IL-6 levels were measured in supernatant by ELISA kit. Gene expressions of pro-inflammatory cytokines, namely IL-6, IL-8, TNF-α, IL-1β, IL-4, IL-10, IL-17, IL-21, and IFN-γ, were measured by qPCR. IL-6 secretion levels and gene expressions were compared statistically between groups by Student's t test. Forty-seven patients were screened. Eight patients satisfied ACR/EULAR criteria for pSS. Seven patients with absent glandular inflammation and negative serology constituted sicca controls. These 15 subjects were included in final analysis. In pSS group, but not in controls, median IL-6 levels in supernatant were less in curcumin-treated as compared to PHA-alone subset [5.5 (0.7-13.34) vs 18.3 (12-32) ng/ml; p = 0.0156]. mRNA expression levels of IL-6 were also lower in curcumin-treated samples as compared to PHA alone, when cases and controls were analyzed together as well as in cases alone (p = 0.0009 and p = 0.0078, respectively); however, mRNA expression of IL-1β was lower in curcumin-treated samples as compared to PHA alone, only when cases and controls were analyzed together (p = 0.0215). There was no difference in other cytokine gene expression levels between the subsets under the in-vitro experimental conditions. In conclusion, curcumin reduced mRNA expression as well as secretion of IL-6 levels by salivary gland tissue of patients with pSS. Curcumin also suppressed PHA-induced mRNA expression levels of IL-6 and IL-1β in MSG tissue of patients with pSS and controls when analyzed together as a combined group.
32842840 Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and n 2022 Apr PURPOSE: Only five patients diagnosed with transverse myelitis (TM) associated with primary biliary cirrhosis (PBC) have been reported in the literature to date. We report two additional patients with TM associated with PBC at our hospital and review all seven cases. MATERIALS AND METHODS: An association between neuromyelitis optic spectrum disease (NMOSD) and PBC is reported for the first time in one of our patients. The second patient was diagnosed with TM associated with PBC without Sjögren's syndrome (SS). A literature review was performed using the PubMed database. RESULTS: All patients diagnosed with TM associated with PBC were female with a median age of 53 years. TM was associated with SS in 71.4% of the patients. Complete TM and incomplete TM were diagnosed in 71.4% and 28.6% of the patients. The erythrocyte sedimentation rate was increased in 83.3% of patients. All patients were positive for anti-mitochondrial antibodies. Other autoantibodies, including anti-nuclear antibodies, rheumatoid factor, anti-SSA antibody, were detected in some patients. Cerebrospinal fluid analysis was abnormal in 83.3% of patients. The spinal cord lesions involved more than three vertebral segments in 85.7% of patients. Glucocorticoids were administered in 85.7% of patients, and good responses were observed. CONCLUSIONS: The association between TM and PBC may be missed by neurologists. More attention should be paid to the association between NMOSD and PBC. Most patients show SS and may experience relapse, and there is a good rationale for early commencement of immunosuppressive therapy.