BACKGROUND: (1) Influence of comorbidities on life expectancy and treatment outcomes is one of the main concerns of modern rheumatology, due to their rising prevalence and increasing impact on mortality and disability. The main objective of our study was to analyze the time trends and shifts in the comorbidity profile and mortality over 10 years in the Polish population with ankylosing spondylitis (AS). (2) Data from 2011-2020 years were acquired from the General Hospital Morbidity Study in the National Institute of Public Health-National Institute of Hygiene (NIH-PIB) as ICD-10 codes. Based on ICD10 codes, we calculated the percentage shares for comorbidities, with the relative risk ratios and odds ratios. We analyzed the hospitalization rates and mortality from the overlapping conditions. Also, we analyzed age and sex related differences in the clinical manifestations of AS patients. (3) Results: From 53,142 hospitalizations of patients with AS, we found that the male population presented higher rates of cardiovascular (2.7% vs. 1.3% p < 0.001) and pulmonary conditions (1.2% vs. 0.8% p < 0.025). Inflammatory bowel diseases were more common in the female population than in males (2.3% vs. 1.7%, p < 0.001). In the years 2011-2020, we observed a decline in the number of hospitalized patients due to cardiovascular (p < 0.001) and respiratory system conditions (p < 0.001), yet the relative risk and odd ratios remained high. In the years 2011-2020, 4056 patients received biological treatment (7%). The number of initiated biological therapies correlated negatively with the number of reported hospitalizations due to ischemic heart diseases (IHD) (p < 0.031, r = -0.8). Furthermore, in the logistic regression model, we found strong collinearity between cardiovascular and pulmonary comorbidities (VIF = 14; tolerance = 0.1); also, the number of reported IHD's correlated positively with the number of pulmonary infections (p < 0.031, r = 0.7) (4). CONCLUSIONS: Cardiopulmonary comorbidities are a main factor associated with increased mortality in patients with AS, especially in hospitalized patients. The mortality rates among patients with AS admitted to hospital due to other conditions other than movement disorders exceed the populational risk. The number of biologically treated patients correlated negatively with hospital admissions due to IHD.
OBJECTIVES: To present a personalized approach in three cases of treatment-resistant, locoregionally aggressive forms of cANCA-positive granulomatosis with polyangiitis (GPA) and skull base involvement. METHODS: Three patients with GPA and skull base involvement were described alongside a critical review of the current literature. RESULTS: All presented patients suffered from GPA with an inflammatory tumor at the skull base, alongside cerebellopontine angle involvement, cranial nerve palsies, cerebellar disorders, concomitant hearing loss, and severe otalgia. Symptoms were associated with progressive granulomatous destruction of the temporal bone, laryngopharynx, and central nervous system infiltration. Treatment with cyclophosphamide and high doses of glucocorticoid steroids were ineffective but subsequent therapy with rituximab was successful in the presented cases. The literature review showed that the course of the disease with skull base involvement is associated with poorer clinical and radiological responses to standard pharmacotherapies. CONCLUSION: Granulomatous inflammation localized in the skull base is associated with a more aggressive disease progression and is less likely to respond to pharmacotherapy. Standard induction therapy with cyclophosphamide and glucocorticoid steroids may be ineffective. A better response may be achieved by using rituximab and concomitant local treatment with glucocorticoid steroid injections.
Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.
Arthritis , COVID-19 , Humans , COVID-19 Vaccines , BNT162 Vaccine , Interleukin-17 , COVID-19/prevention & control , Immunoglobulin G , Vaccination , Antibodies, Viral
Introduction: Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA). Patients and methods: 49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine. Results: After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine. Conclusion: Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.
Arthritis , COVID-19 , Rheumatic Diseases , Humans , Immunization, Secondary , COVID-19 Vaccines , Prospective Studies , BNT162 Vaccine , COVID-19/prevention & control , Vaccination
This study aimed to investigate the associations of microRNA (miRs) signatures with cytokines, serum lipids, and disease activity in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). In total, 65 patients (PsA n = 25, AS n = 25, RA n = 15) and 25 healthy controls (HC) were enrolled into the study. The expression of miR-223-5p, miR-92b-3p, miR-485-3p, miR-10b-5p, let-7d-5p, miR-26a-2-3p, miR-146b-3p, and cytokines levels were measured in sera. DIANA-mirPath analysis was used to predict pathways targeted by the dysregulated miRs. Disease activity scores were calculated. Lipid profile, uric acid, glucose level, and C-reactive protein (CRP) concentrations were determined in the blood. Based on lipid profiles, the PsA group had hypertriglyceridaemia, and RA patients revealed mixed dyslipidaemia, while in AS, no specific changes were found. miR expression analysis revealed upregulation of miR-26a-2-3p and miR-10b-5p in PsA, miR-485-3p in AS, and let-7d-5p in RA. Several correlations between disease activity indexes, metabolites levels, and expression of miRs were observed in PsA, RA, and AS patients. Finally, in ROC analysis, miR-26a-2-3p/miR-485-3p, and let-7d-5p/miR-146b-3p tandems revealed high sensitivity and specificity in distinguishing between PsA, AS, and RA. Our study illustrates the superiority of miR expressions in distinguishing between RA, PsA, and AS. In PsA, a unique regulatory pathway exists through miR-26a-2-3p, miR-223-5p, miR-10b-5p, and miR-92b-3p that converges proatherogenic metabolism and disease activity.
OBJECTIVE: To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. METHODS: 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. RESULTS: Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho = -0.37 and rho = -0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.
OBJECTIVE: To explore global miRNA and transcriptomic profiling of monocytes from RA patients compared with healthy controls in order to predict which aberrantly expressed miRNA can negatively modulate inflammatory molecules. METHODS: Using next-generation sequencing, we have performed simultaneous global analysis of miRNA (miRNA-seq) and transcriptome (RNA-seq) of monocytes from RA patients and healthy controls. Global analysis of miRNA of SSc monocytes was also performed. Following differential analysis and negative correlation, miRNA-RNA pairs were selected. RESULTS: We found that 20 specific miRNA candidates are predicted to silence inflammatory mediators, out of 191 significantly changed miRNAs in RA monocytes. Based on the highest scoring in terms of negative correlation (r = -0.97, P = 1.75e-07, false discovery rate = 0.04) and the number of seeds in miRNA responsible for negative regulation, we selected miRNA-146b and its target gene anti-inflammatory retinoic acid receptor alpha (RARA). Similarly to next-generation sequencing, qPCR analysis also confirmed negative correlation between miRNA-146b and RARA expression (r = -0.45, P = 0.04). Additionally, miRNA-146b expression in RA monocytes significantly correlated with clinical parameters including DAS28 for RA with CRP (DAS28-CRP) and ESR (DAS28-ESR), whereas overexpression of miRNA-146b was able to functionally reduce RARA expression in the human monocytic cell line THP-1. Finally, circulating miRNA-146b expression in sera and SFs was significantly elevated in RA patients. CONCLUSIONS: Overall, in this study we have identified a new miRNA-146b candidate that is predicted to negatively regulate the anti-inflammatory RARA transcript, whereas circulating miRNA-146b level can be used as a biomarker predicting pro-inflammatory RA progression and disease activity.
Arthritis, Rheumatoid/metabolism , MicroRNAs/blood , Monocytes/metabolism , Case-Control Studies , Cell Line , Disease Progression , Gene Expression Profiling , Gene Expression Regulation , Humans , Retinoic Acid Receptor alpha/genetics , Synovial Fluid/metabolism , Transcriptome
OBJECTIVES: T-cell-mediated adaptive immunity contributes to the development and persistence of ankylosing spondylitis (AS). Mesenchymal stromal/stem cells (MSCs) have immunomodulatory potential and are able to inhibit T-cell proliferation, but their functionality in AS patients is relatively unknown. The aim of the study was to assess the direct anti-proliferative effects of MSCs isolated from subcutaneous abdominal adipose tissue of AS patients (AS/ASCs) on allogeneic T lymphocytes, using commercially available ASC lines from healthy donors (HD/ASCs) as a control. MATERIAL AND METHODS: CD3+CD4+ T-cells were isolated from peripheral blood of healthy blood donors, activated with anti-CD3/CD28 beads, and co-cultured for 5 days with untreated and TNF+IFN-γ pre-stimulated HD/ASCs (5 cell lines) and AS/ASCs, obtained from 11 patients (6F/5M). The proliferative response of T-cells was analysed by flow cytometry, while the concentrations of kynurenines, prostaglandin E2 (PGE-2), interleukin 10 (IL-10), and interleukin 1 receptor antagonist (IL-1Ra) were measured spectrophotometrically or using a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: HD/ASCs and AS/ASCs similarly reduced the T-cell proliferation response, i.e. the percentage of proliferating cells, the proliferation, and replication indices, and these effects were dependent mostly on soluble factors. In the co-cultures of activated CD4+ T-cells with HD/ASCs and AS/ASCs significant increases of kynurenines, PGE-2, and IL-1Ra, but not IL-10, production were observed. The release of these factors was dependent either on cell-to-cell contact (IL-10, IL-1Ra) or soluble factors (kynurenines, PGE-2). There was a moderate to strong negative correlation between T-cell proliferative response, and the concentrations of kynurenines, PGE-2, and IL-10, but not IL-1Ra. This association was more evident in the case of TI-treated AS/ASCs than HD/ASCs. CONCLUSIONS: AS/ASCs, similar to HD/ASCs, exert a direct effective anti-proliferative impact on CD4+ T cells, acting via soluble factors that are released in cell contact-dependent (IL-10) and independent (kynurenines, PGE-2) pathways. Thus, our results suggest that AS/ASCs are potentially useful for therapeutic application.
BACKGROUND: In ankylosing spondylitis (AS), accompanied by chronic inflammation, T cell expansion plays a pathogenic role; the immunoregulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) are impaired, while functional characteristics of their adipose tissue-derived counterparts are (ASCs) unknown. METHODS: We evaluated the antiproliferative activity of AS/ASCs, obtained from 20 patients, towards allogeneic and autologous T lymphocytes, using ASCs from healthy donors (HD/ASCs) as the reference cell lines. The PHA-activated peripheral blood mononuclear cells (PBMCs) were cocultured in cell-cell contact and transwell conditions with untreated or TNF + IFNγ- (TI-) licensed ASCs, then analyzed by flow cytometry to identify proliferating and nonproliferating CD4+ and CD8+ T cells. The concentrations of kynurenines, prostaglandin E2 (PGE2), and IL-10 were measured in culture supernatants. RESULTS: In an allogeneic system, HD/ASCs and AS/ASCs similarly decreased the proliferation of CD4+ and CD8+ T cells and acted mainly via soluble factors. The concentrations of kynurenines and PGE2 inversely correlated with T cell proliferation, and selective inhibitors of these factors synthesis significantly restored T cell response. AS/ASCs exerted a similar antiproliferative impact also on autologous T cells. CONCLUSION: We report for the first time that despite chronic in vivo exposure to inflammatory conditions, AS/ASCs retain the normal capability to restrain expansion of allogeneic and autologous CD4+ and CD8+ T cells, act primarily via kynurenines and PGE2, and thus may have potential therapeutic value. Some distinctions between the antiproliferative effects of AS/ASCs and HD/ASCs suggest in vivo licensing of AS/ASCs.
The domination of pro-inflammatory Th subsets (Th1, Th17) is characteristic of ankylosing spondylitis (AS). Mesenchymal stem cells (MSC) were reported to normalize Th imbalance, but whether MSCs from AS adipose tissue (AS/ASCs) possess such properties is unknown. We examined AS/ASCs' impact on Th-cell differentiation, using healthy donors ASCs (HD/ASCs) as a control. The assessment of the expression of transcription factors defining Th1 (T-bet), Th2 (GATA3), Th17 (RORc), and Treg (FoxP3) subsets by quantitative RT-PCR, the concentrations of subset-specific cytokines by ELISA, and Treg (CD4+CD25highFoxP3+) formation by flow cytometry, were performed in the co-cultures of ASCs with activated CD4+ T cells or peripheral blood mononuclear cells (PBMCs). AS/ASCs and HD/ASCs exerted similar immunomodulatory effects. Acting directly on CD4+ T cells, ASCs decreased the T-bet/GATA3 and RORc/FoxP3 ratios, diminished Treg formation, but increase IFNγ and IL-17AF production, while ASCs co-cultured with PBMCs enhanced Treg generation and reduced IFNγ release. ASCs failed to up-regulate the anti-inflammatory IL-10 and TGFß. AS/ASCs' impact on allogeneic and autologous PBMCs was similar. In conclusion, to shift Th differentiation to a functional anti-inflammatory direction, ASCs require accessory cell support, whereas their direct effect may be pro-inflammatory. Because ASCs neither inhibit IL-17AF nor up-regulate anti-inflammatory cytokines, their usefulness for AS patients' treatment remains uncertain.
Adipose Tissue/metabolism , Mesenchymal Stem Cells/metabolism , Spondylitis, Ankylosing/genetics , Th1 Cells/metabolism , Cell Differentiation , Female , Humans , Male , Spondylitis, Ankylosing/pathology
Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially in those rheumatoid arthritis (RA) patients, who did not adequately respond to conventional synthetic DMARD therapy. However, despite the proven efficacy, the high cost of the therapy resulted in limitation of the widespread use and unequal access to the care. The introduction of biosimilars, which are much cheaper relative to original drugs, may facilitate the achievement of the therapy by a much broader spectrum of patients. In this review we present the properties of original biologic agents based on cytokine-targeted (blockers of TNF, IL-6, IL-1, GM-CSF) and cell-targeted therapies (aimed to inhibit T cells and B cells properties) as well as biosimilars used in rheumatology. We also analyze the latest update of bDMARDs' possible influence on DNA methylation, miRNA expression and histone modification in RA patients, what might be the important factors toward precise and personalized RA treatment. In addition, during the COVID-19 outbreak, we discuss the usage of biologicals in context of effective and safe COVID-19 treatment. Therefore, early diagnosing along with therapeutic intervention based on personalized drugs targeting disease-specific genes is still needed to relieve symptoms and to improve the quality of life of RA patients.
Antirheumatic Agents , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , COVID-19 Drug Treatment , Drug Repositioning , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Epigenesis, Genetic , Humans
BACKGROUND: Activated T lymphocytes play an important role in the pathogenesis of rheumatic diseases (RD). Mesenchymal stem cells (MSCs) possess immunoregulatory activities but such functions of MSCs from bone marrow of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and ankylosing spondylitis (AS) patients are impaired. Adipose tissue-derived MSCs (ASCs) are an optional pool of therapeutically useful MSCs, but biology of these cells in RD is poorly known. This study aimed at investigating the effect of ASCs from RD patients and healthy donors (HD) on the expression of the key T-cell activation markers. METHODS: ASCs were isolated from subcutaneous abdominal fat from SLE (n = 16), SSc (n = 18), and AS (n = 16) patients, while five human ASCs lines from HD were used as a control. Untreated and cytokine (tumor necrosis factor α + interferon γ)-treated ASCs were co-cultured with allogenic, mitogen (phytohemagglutinin)-stimulated peripheral blood mononuclear cells (PBMCs) or purified anti-CD3/CD28-activated CD4+ T lymphocytes. Contacting and noncontacting ASCs-PBMCs co-cultures were performed. RD/ASCs were analyzed in co-cultures with both allogeneic and autologous PBMCs. Flow cytometry analysis was used to evaluate expression of CD25, HLA-DR, and CD69 molecules on CD4+ and CD8+ cells. RESULTS: In co-cultures with allogeneic, activated CD4+ T cells and PBMCs, HD/ASCs and RD/ASCs downregulated CD25 and HLA-DR, while upregulated CD69 molecules expression on both CD4+ and CD8+ cells with comparable potency. This modulatory effect was similar in contacting and noncontacting co-cultures. RD/ASCs exerted weaker inhibitory effect on CD25 expression on autologous than allogeneic CD4+ and CD8+ T cells. CONCLUSION: RD/ASCs retain normal capability to regulate expression of activation markers on allogeneic T cells. Both HD/ASCs and RD/ASCs exert this effect independently of their activation status, mostly through the indirect pathway and soluble factors. However, autologous CD4+ and CD8+ T cells are partially resistant to RD/ASCs inhibition of CD25 expression, suggesting weaker control of T-cell activation in vivo.
Lymphocyte Activation/physiology , Mesenchymal Stem Cells/metabolism , Rheumatic Diseases/genetics , Adult , Aged , Cells, Cultured , Female , Humans , Male , Middle Aged , T-Lymphocytes , Young Adult
Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-ß1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-γ (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE2), IL-6, leukemia inhibiting factor (LIF), and TGF-ß1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient's erythrocyte sedimentation rate (ESR) value. IFN-α and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-ß1 up-regulated PGE2 secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs.
Mesenchymal Stem Cells/metabolism , Rheumatic Diseases/metabolism , Adipose Tissue/cytology , Adipose Tissue/metabolism , Adipose Tissue/physiology , Adult , Cells, Cultured , Cytokines/metabolism , Dinoprostone/metabolism , Female , Humans , Inflammation Mediators/metabolism , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6/metabolism , Male , Mesenchymal Stem Cells/physiology , Middle Aged , Phenotype , Steryl-Sulfatase/metabolism , T-Lymphocytes, Regulatory/metabolism , Thy-1 Antigens/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
Various silicon compounds have been reported to stimulate autoimmune reactions in the human body. Based on case reports, a possible causal association between silicone breast implants and systemic sclerosis has been suggested since the end of the 1970s. Although the relationship between systemic sclerosis and silicone breast implants has been intensely investigated, no clear evidence of such an association has ever been found in epidemiological studies. Instead, it is now proposed that silicone breast implants can induce nonspecific symptoms of inflammatory diseases, despite not fulfilling the diagnostic criteria for a specific autoimmune disease. This phenomenon was named autoimmune syndrome induced by adjuvants (ASIA syndrome). ASIA syndrome is worth considering in the differential diagnosis in rheumatology patients. In this paper, we present a case of the scleroderma-like syndrome in a 48-year-old woman with a broken silicone breast implant and a review the current literature on this issue.
In this study, we analysed the expression level of sera circulating miRNA-5196 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients before and after tumor necrosis factor (TNF)-α therapy as biomarkers predicting positive treatment outcome. We enrolled 10 RA patients, 13 AS patients, and 12 healthy individuals in the study. The expression of miRNA-5196 was measured by real-time polymerase chain reaction before and after anti-TNF-α therapy. Disease activity of RA patients was assessed using disease activity score 28 (DAS28), whereas ankylosing spondylitis DAS (ASDAS) was used in AS patients. MiRNA-5196 expression was significantly higher in patients with RA and AS before TNF-α therapy than in those following anti-TNF-α therapy and healthy controls. Changes in miRNA-5196 expression positively correlated with delta DAS28 or delta ASDAS, respectively, following TNF-α therapy. In contrast, changes in C-reactive protein (CRP) levels in RA and AS patients did not positively correlate with DAS28 or ASDAS changes. Receiver-operating characteristic analysis showed better diagnostic accuracy of miRNA-5196 expression both in RA (area under curve (AUC) = 0.87, p = 0.055) and AS patients (AUC = 0.90, p = 0.050) compared to CRP levels in RA (AUC = 0.75, p = 0.201) and AS patients (AUC = 0.85, p = 0.086) upon biologic therapy treatment. Finding novel biomarkers, including miRNA-5196 which allow to predict and monitor anti-TNF-α response, would be of clinical value especially during the early phase of RA or AS development.
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Gene Expression Regulation/drug effects , MicroRNAs/genetics , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/pharmacology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/genetics , Biomarkers/blood , C-Reactive Protein/analysis , Female , Humans , Male , MicroRNAs/blood , Middle Aged , Real-Time Polymerase Chain Reaction , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/genetics
The current methods of cardiovascular (CV) risk assessment in the course of inflammatory connective tissue diseases are a subject of considerable controversy. Comparing different methods of CV risk assessment in current rheumatoid arthritis (RA) guidelines, only a few of them recommend the use of formal risk calculators. These are the EULAR guidelines suggesting the use of SCORE and the British Society for Rheumatology guidelines performed in collaboration with NICE preferring the use of QRISK-2. Analyzing the latest American and British reports, two main concepts could be identified. The first one is to focus on risk calculators developed for the general population taking into account RA, and the calculator that might fulfill this role is the new QRISK-2 presented by NICE in 2014. The second concept is to create RA-specific risk calculators, such as the Expanded Cardiovascular Risk Prediction Score for RA. In this review we also discuss the efficiency of a new Pooled Cohort Equation and other calculators in the general and RA population.
