The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

PPARγ partial agonist LPSF/GQ-16 prevents dermal and pulmonary fibrosis in HOCl-induced systemic sclerosis (SSc) and modulates cytokine production in PBMC of SSc patients.

Thiazolidinediones (TZD) are synthetic molecules that have a range of biological effects, including antifibrotic and anti-inflammatory, and they may represent a promising therapeutic strategy for systemic sclerosis (SSc). The aim of this study was to investigate the immunomodulatory and antifibrotic properties of LPSF/GQ-16, a TZD derivative, in peripheral blood mononuclear cells (PBMC) from SSc patients and in a murine model of SSc HOCl-induced. The PBMC of 20 SSc patients were stimulated with phytohemagglutinin (PHA) and treated with LPSF/GQ-16 for 48 h, later cytokines in the culture supernatants were quantified by sandwich enzyme-linked immunosorbent assay (ELISA) or cytometric bead array (CBA). Experimental SSc was induced by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. HOCl-induced SSc mice received daily treatment with LPSF/GQ-16 (30 mg/kg) through intraperitoneal injections during the same period. Immunological parameters were evaluated by flow cytometry and ELISA, and dermal and pulmonary fibrosis were evaluated by RT-qPCR, hydroxyproline dosage and histopathological analysis. In PBMC cultures, it was possible to observe that LPSF/GQ-16 modulated the secretion of cytokines IL-2 (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.001), IL-17A (p = 0.006), TNF (p < 0.001) and IFN-γ (p < 0.001). In addition, treatment with LPSF/GQ-16 in HOCl-induced SSc mice promoted a significant reduction in dermal thickening (p < 0.001), in the accumulation of collagen in the skin (p < 0.001), down-regulated the expression of fibrosis markers in the skin (Col1a1, α-Sma and Tgfß1, p < 0.001 for all) and lungs (Il4 and Il13, p < 0.001 for both), as well as reduced activation of CD4 + T cells (p < 0.001), B cells (p < 0.001) and M2 macrophages (p < 0.001). In conclusion, LPSF/GQ-16 showed immunomodulatory and antifibrotic properties, demonstrating the therapeutic potential of this molecule for SSc.

Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network).

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Association between autoimmune rheumatic diseases and head and neck cancer: Systematic review and meta-analysis.

BACKGROUND: Personal history of autoimmune rheumatic diseases has been implicated in the development of malignant neoplasms. Our aim was to assess the risk of head and neck (H&N) cancers in patients with autoimmune rheumatic diseases. METHODS: The articles search included PubMed, EMBASE, LILACS, The Cochrane Library, CINAHL, Scopus, Web of Science, and Google Scholar with no language restrictions for studies published from inception of the databases to August 20, 2022, assessing the risk of H&N cancer in patients with autoimmune rheumatic diseases. Studies were included if they reported the standardized incidence ratio (SIR) with corresponding 95% confidence intervals (CIs). The primary outcome was risk of H&N cancers in patients with autoimmune rheumatic diseases compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of H&N cancers varied according to study site. RESULTS: Our search identified 5378 records, of which 32 cohort studies were eligible for systematic review and 24 for meta-analysis (including 273 613 patients). A significant association was found between H&N cancer and autoimmune rheumatic diseases (SIR = 2.35; 95% CI: 1.57-3.50; p < 0.01, I2  = 94%). CONCLUSION: Our study suggests that patients with autoimmune rheumatic diseases had a significantly increased risk of H&N cancer compared with the general population, including thyroid, oral, and nasopharyngeal cancers. These findings have implications for the individualized screening of these patients and the planning of oncology units. The protocol is registered with PROSPERO, number CRD42020197827.

Vitamin D receptor gene polymorphisms influence on clinical profile and bone mineral density at different skeletal sites in postmenopausal osteoporotic women.

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age-matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A = 0.828 ± 0.09; A/G = 0.081 ± 0.13; G/G = 0.876 ± 0.12, p = .039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR] = 5.12, 95% confidence interval [CI ]= 1.13-23.27, p = .012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR = 0.24, 95%CI = 0.06-0.94, p = .029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD.

Association between axial spondyloarthritis and temporomandibular disorders: A systematic review.

This study aimed to assess the frequency of temporomandibular disorders (TMDs) in patients with axial spondyloarthritis (axSpA) compared with the healthy individuals. We systematically searched PubMed, Embase, Scopus, Web of Science, CINAHL, and Google Scholar databases from their inception until 2022, without language restriction. A standardized dataset was used to extract data from the observational studies. Patients were required to have axial spondyloarthritis and clinical and/or radiographic evidence of temporomandibular joint dysfunction. Meta-analysis was performed with a random effects model. A systematic review was registered under number CRD42020206283. We identified seven relevant studies, which provided data for 745 patients and 216 temporomandibular disorders events. The combined odds ratio (OR) showed that the risk of temporomandibular disorders in individuals with axial spondyloarthritis was higher than the control group (pooled OR = 5.26, 95% CI 2.50-11, 06; p < 0.02; I2  = 58%). Also, these individuals do not appear to refer possible temporomandibular joint symptoms to the rheumatologist or dentist. The results of this systematic review and meta-analysis suggest that patients with axial spondyloarthritis have an increased frequency of temporomandibular disorders. TMDs seem to be secondary to postural alterations rather than direct involvement of the temporomandibular joints (TMJs).

Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Adverse post-operative events of salivary gland biopsies: A systematic review and meta-analysis.

OBJECTIVES: The study aimed to perform a systematic review and meta-analysis of the complications following major and minor salivary gland biopsy. MATERIALS AND METHODS: Observational studies assessing postoperative complications of minor salivary gland biopsy and indexed at Medline/PubMed, EMBASE, Cinahl, LILACS, or Scopus were selected. This review was registered under the protocol number: CRD42020211169. The level of significance considered was 0.05, and the R software (The R Foundation) was used for the meta-analysis. RESULTS: Twenty-seven studies reporting 3208 patients were included in this review. The combined prevalence of postsurgical complications was 11% (95% CI, 8 to 13%, p = 0.01). The percentage of the combined prevalence of neurological complications was 3% (95% CI, 1-6%, p = 0.01). The surgical technique did not influence the frequency of overall and neurological complications. CONCLUSION: Minor salivary gland biopsies are a safe and predictable procedure that should be performed on the lower lip. Postoperative complications are more common than previously reported, but permanent complaints are uncommon.

Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3 ) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, p = .01) and G/G genotype (OR = 2.69, p = .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, p = .01; OR = 0.46, p = .01; OR = 0.44, p = .02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR = 0.31, p = .01); rs4760648 T/T genotype and photosensitivity (OR = 0.24, p = .02); rs1540339 T/T genotype and antibody anti-dsDNA (OR = 0.19, p = .015); rs3890733 T/T genotype and serositis (OR = 0.10, p = .01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p = 1.04e-7 ), in Cdx-2 A/G and G/G (p = .008 and p = .014, respectively) and in patients with nephritis (p = .016) Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.

Joint mobilization and therapeutic exercises in the hands of patients with systemic sclerosis: A preliminary randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of Maitland's joint mobilization and therapeutic exercises on the functionality of the hands in patients with systemic sclerosis. DESIGN: Randomized controlled trial. SETTING: Tertiary university hospital. SUBJECTS: Twenty-four patients diagnosed with systemic sclerosis according to ACR/EULAR 2013 criteria; age ⩾18 years and Cochin Hand Functional Scale (COCHIN) score ⩾10. They were randomized to physical therapy group (n = 12) or control group (n = 12). INTERVENTIONS: The physical therapy group received joint mobilization and undertook therapeutic exercises, twice a week, for 12 weeks, and received a booklet with information about the disease. The control group only received the booklet about the disease. MAIN MEASURES: The primary outcome measure was functionality of the hands (COCHIN). The secondary outcomes measures were disability (SHAQ), pain (visual analogic scale), range of motion (HAMIS and Delta finger-to-palm), grip strength (JAMAR dynamometer), and quality of life (SF12). RESULTS: Twenty-two patients were female, with a mean age of 47.4 ± 11.1 years and 18 had limited cutaneous form. The physical therapy group showed a decrease of 11.33 points in the COCHIN in comparison with the control group (P = 0.09). There was a significant increase in range of motion by HAMIS (3.00 ± 1.48 vs 5.42 ± 2.64, P = 0.008), reduction in pain VAS (3.42 ± 2.78 vs 7.75 ± 2.53, P < 0.001), and increase in the physical component of SF12 (38.51 ± 9.60 vs 32.65 ± 9.10, P = 0.038). CONCLUSION: Maitland's joint mobilization and therapeutic exercises improved the functionality of the hands, reduced pain in the hands and wrists, increased range of motion, and improved quality of life in patients with systemic sclerosis.

Differential expression of the inflammasome complex genes in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving heterogeneous clinical manifestations and numerous susceptibility genes. Several findings evidence the critical role of inflammasomes in the predisposition to autoimmune diseases and in SLE. We investigated whether inflammasome polymorphins could affect susceptibility to develop and/or severity SLE. Moreover, differences in inflammasome activation in peripheral blood were also evaluated in SLE patients and controls. The distribution of 13 SNPs in eight inflammasome genes was evaluated. To assess inflammasome priming in peripheral blood monocytes of SLE and controls, differential expression of selected inflammasome genes and IL-1ß production was analyzed in resting condition as well as after LPS and ATP stimulation. Results showed that the gain-of-function variant rs10754558 (NLRP3) was significantly more frequent in SLE patients with nephritis, reinforcing the concept of a key role of NLRP3 inflammasome not only in SLE but also especially in kidney disease. SLE monocytes in resting condition showed a higher level of IL-1ß expression and produced higher levels of IL-1ß when stimulated with LPS+ATP comparing to controls. The stimulation induced a significant expression of NLRP1, AIM2, CASP1, and IL1B genes, suggesting that the NLRP1 inflammasome is responsible for the IL-1ß production observed in monocytes. These data emphasized once more the important contribution of inflammasome in SLE-associated inflammation.

EBV and CMV viral load in rheumatoid arthritis and their role in associated Sjögren's syndrome.

INTRODUCTION: The role of viral infections in the pathogenesis of autoimmune diseases has long been suggested, but little evidence is available. OBJECTIVE: This study aimed to evaluate an association between EBV and CMV and the presence of rheumatoid arthritis and its association with Sjögren's Syndrome. PATIENTS AND METHOD: A case-control study was performed with 227 patients divided in RA (n = 99), RA/SS (n = 20), and C (n = 128). Resting salivary flow rate and Schirmer's test were performed; minor salivary gland biopsy was indicated in the case of suspected Sjögren's syndrome. CMV and EBV viral loads were quantified in peripheral blood, and their presence in glandular tissue samples was evaluated by in situ hybridization (EBV) and immunohistochemistry (CMV). RESULTS: EBV was more frequent in RA and RA/SS than in C (P < .000007). No correlation with clinical markers (P > .05) or between RA and RA/SS was found (P > .05). A higher number of EBV/DNA copies were found in RA (158.52 copies/µL) and RA/SS (99.24 copies/µL) (P = .739). EBV/DNA was associated with the Schirmer test (P = .0231). CMV was detected in one patient of the RA group. None of the viruses were detected in biopsies of minor salivary glands. CONCLUSIONS: Detection of EBV/DNA in peripheral blood was associated with RA regardless of the presence of SS.

Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs-Data From the Brazilian Registry for Biologics Monitoring.

BACKGROUND: The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES: The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS: BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS: A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS: In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.

CCL3, IL-7, IL-13 and IFNγ transcripts are increased in skin's biopsy of systemic sclerosis.

Although several cytokines and chemokines have been investigated as possible mediators of fibrosis in systemic sclerosis (SSc), specific correlation between cytokines and organ involvement have not been found yet, and a cytokine profile characteristic of SSc is far to be identified. We studied the profile of antifibrotic and profibrotic transcripts involved in skin of SSc patients. The mRNA expression was detected by fluorescence-based quantitative real-time PCR (qPCR) in skin's biopsies from 14 patients with SSc and 5 healthy controls. PDGF-A, CTGF, CCL3, IL-6, IL-13, IL-7, IFNγ, IL-17, IL-22 and RORc were analysed in these samples. CCL3, IL-7, IL-13 and IFN-γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls. We also found a positive correlation between CCL3 and IL-7 transcripts (P = 0.0050 r = 0.7187). Furthermore, we observed that patients with lung involvement had lower expression of PDGF-A (P = 0.0385). We found an increase in IL-7, IFN-γ, CCL3 and IL-13 relative mRNA expressions on the skin's biopsy of patients with SSc, and a positive correlation between IL-7 and CCL3. These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies.

Oral features of systemic sclerosis: A case-control study.

OBJECTIVE: The aim of this study was to evaluate the orofacial parameters of systemic sclerosis (SSc) and its related systemic features. SUBJECTS AND METHODS: A descriptive case-control study was performed from November 2015 to October 2016. Ninety-three individuals were included and divided into SSc group (n = 50) and healthy controls (C, n = 43). RESULTS: Systemic sclerosis individuals were mostly women (43/50, 86%), with a mean age of 46 years (±11.6 years). Telangiectasia (42/50, 84%) and reduced mouth opening (35/50, 70%) were the most frequent orofacial findings. The periodontitis frequency was much higher in SSc individuals than in healthy controls (90.7% × 48.83%; p < .001). In addition, SSc individuals presented a distinctive pattern of periodontitis, with low probing pocket depth (2 ± 0.65 mm × 2 ± 0.24; p < .001), higher gingival recession (4 ± 2.13 × 0.14 ± 0,22; p < .001), higher periodontal attachment loss (6 ± 1.34 mm × 2 ± 0.43, p < .001), and lower gingival bleeding index values (7.05 ± 7.25 × 21.57 ± 15.66; p < .001). CONCLUSIONS: Orofacial manifestations were common in SSc and included a unique pattern of periodontal manifestation, characterized by lower gingival bleeding index, higher periodontal attachment loss, and low probing depth.

Pilates method in the treatment of patients with Chikungunya fever: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of the Pilates method on the reduction of pain, improvement of joint function, and quality of life of patients with chronic Chikungunya fever. DESIGN: This is a randomized, controlled, blind trial for the evaluators. SETTING: The study was conducted at the Advanced Laboratory in Physical Education and Health at Federal University of Pernambuco, Brazil. SUBJECTS: A total of 51 patients were allocated randomly and divided into 2 groups: a Pilates group (26 patients) and a control group (25 patients). After 12 weeks, 4 patients in the Pilates group and 5 in the control group were lost to follow-up. INTERVENTION: The Pilates group performed 24 Pilates method intervention sessions; the control group continued to receive standard clinical treatment at the outpatient clinic. MAIN MEASURES: The main measures were as follows: visual analogue scale (VAS) for pain, functional capacity evaluated by Health Assessment Questionaire (HAQ), quality of life measured by the 12-Item Short-Form Health Survey (SF-12), and range of joint motion by goniometry. RESULTS: After 12 weeks, patients in the Pilates group presented lower VAS (P < 0.001), lower HAQ scores (P < 0.001), and higher quality-of-life scores (P < 0.001) compared with the control group. We found statistically significant results for the Pilates group in the range of movement for shoulder, knee, ankle, and lumbar spine (P < 0.001). In the intragroup analysis, there was a significant improvement in all outcomes evaluated. CONCLUSION: In this study, patients undertaking Pilates method for 12 weeks had less pain, better function and quality of life, and increased range of joint movement.

Dexamethasone inhibits cytokine production in PBMC from systemic sclerosis patients.

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1ß were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1ß (p < 0.001 for all), and IL-17F (p = 0.023) cytokines levels. We did not observe differences in response to in vitro treatment with DEX between groups of patients taking or not taking corticosteroids. In PBMC from healthy volunteers, we observed that DEX treatment significantly reduced IL-4, IFN-γ (p = 0.003 for both), IL-6, IL-10, IL-17A, and TNF (p = 0.002 for all) cytokines. These results show that DEX treatment in PBMC of SSc patients reduced the production of important cytokines involved in the pathogenesis of the disease, suggesting a possible mechanism of action of the CG in the treatment of SSc.

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.

OBJECTIVE: In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)'s development and severity in the Brazilian population. MATERIALS AND METHODS: Thirteen single nucleotide polymorphisms within six inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1) as well as IL1B and IL18 genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS + ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR. RESULTS: Our results showed that rs10754558 NLRP3 and rs2043211 CARD8 polymorphisms are associated with RA development (p value = 0.044, OR = 1.77, statistical power = 0.999) and severity measured by Health Assessment Questionnaire (HAQ) (p value = 0.03), respectively. Gene expression analyses showed that RA patients display activation of CASP1, IL1B and IL1R genes independently of LPS + ATP activation. In LPS + ATP-treated monocytes, NLRP3 and NLRC4 expressions were also significantly higher in patients compared with controls. CONCLUSIONS: The first reported results in Brazilian populations support the role of inflammasome in the development of RA.