Safety of esthetic procedures in rheumatic patients: single-center survey of patients.

The popularity of esthetic medicine is growing every year, also among patients with autoimmune inflammatory rheumatic diseases (AIRD). The objective of this study was to evaluate the safety of esthetic medicine (AM) procedures in patients with AIRD. A semi-structured, anonymous questionnaire regarding rheumatic and concomitant diseases and AM procedures was distributed among adult patients hospitalized in the rheumatology department or attending outpatient clinic in the National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw. The main outcome was the occurrence of an adverse event. A number of 512 patients took part in the survey and 15 were excluded (AM procedure preceded the diagnosis of AIRD). The study group consisted of 497 patients, of whom 47 had undergone AM procedures. The procedures performed included: tattooing (22 patients), piercing (16 patients), hyaluronic acid (7 patients), botulinum toxin (5 patients) injections, laser procedures (6 patients), plastic surgery (4 patients), mesotherapy (3 patients) and others. The vast majority of patients had these performed during remission or low disease activity. 70.2% of patients received treatment with disease-modifying antirheumatic drugs (DMARDs) during the AM procedure, with TNF-alfa inhibitors being the most common (63.6%). Adverse events occurred in 15% of patients. All were mild and transient site reactions. Most patients would like to repeat the AM procedure in the future. The use of esthetic medicine procedures in patients with AIRD, including those treated with biologic DMARDs, was associated with a risk of mild site reactions. Most of the patients expressed satisfaction with the results of the AM procedure.

The failure of biological treatment in axial spondyloarthritis is linked to the factors related to increased intestinal permeability and dysbiosis: prospective observational cohort study.

BACKGROUND: A significant number of patients with axial spondyloarthritis (axSpA) do not respond to biological therapy. Therefore, we decided to investigate the specificity of this group of patients and, in particular, whether haptoglobin (Hp), its polymorphism and zonulin, in addition to other clinical features, are predictors of poor response to biological treatment. METHODS: 48 patients with axSpA who were unsuccessfully treated with standard drugs were converted to biological treatment, and from this time on, a 12-week follow-up was started to assess the failure of biological treatment (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decrease < 2 points). Predictors of treatment failure were identified using logistic regression analysis. RESULTS: 21% of subjects had biological treatment failure. Patients who had a higher zonulin level, a history of frequent infections, were older, had inflammatory bowel disease (IBD), had a lower Hp level at the time of inclusion in biological therapy showed an increased risk of treatment failure. CONCLUSIONS: The results of the study support the hypothesis that the effectiveness of biological treatment of axSpA is limited by changed microbiota and intestinal epithelial barrier dysfunction, as an increased risk of biological treatment failure was observed in patients who were older, had higher zonulin level, IBD and repeated courses of antibiotics due to frequent infections. Therefore, starting biological treatment should be followed by reducing intestinal permeability and regulating the disturbed gut microbiome.

Predictors of treatment failure of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis with focus on haptoglobin, haptoglobin polymorphism and zonulin.

According to the Assessment of SpondyloArthritis International Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axial spondyloarthritis (axSpA), patients should undergo at least two courses of non-steroidal anti-inflammatory drugs (NSAIDs) therapy. In our study, we enrolled axSpA patients both at onset and in a flare who had already been treated with NSAIDs ineffectively. Subsequently, according to the recommendations, they received modified NSAID treatment as another attempt to the first-line drug therapy and were monitored from there. We aimed to identify risk factors for treatment failure after 4 weeks (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) especially amongst zonulin and haptoglobin concentrations, and haptoglobin polymorphism. Treatment failure was observed in 71% of patients, and the following variables were contributed for occurrence of this state: higher zonulin levels, ankylosing spondylitis, X-ray sacroiliitis, magnetic resonance imaging sacroiliitis, long duration of symptoms, high BASDAI, and high value of spinal pain intensity on visual analogue scale. In addition, the following positive correlations were found: haptoglobin concentration with C-reactive protein (r = 0.56; p = 0.0004), and erythrocyte sedimentation rate (r = 0.62; p < 0.0001), as well as between zonulin levels and white blood count (r = 0.5; p = 0.0003). The results of the study presented the identified factors related to the standard treatment failure in axSpA, amongst them zonulin levels. They might be applied to point out the patients for whom the search for a more appropriate method of treatment should be considered.

Health-related quality of life impairment is equal for antiphospholipid syndrome whether primary or associated with systemic lupus erythematosus.

Introduction: Antiphospholipid syndrome (APS) manifests with thrombosis and pregnancy losses and may significantly impair the health-related quality of life (HRQoL). So far, APS has been perceived as a less burdensome disease than systemic lupus erythematosus (SLE), but data on this are scarce. The purpose of the present study was to evaluate HRQoL in APS patients by applying the Short Form 36 Health Survey (SF-36) and World Health Organization Quality-of-Life Scale (WHOQoL-BREF); to examine the impact of primary APS and with coexisting SLE (APS/SLE) on patient HRQoL; and to provide a description of the APS patient population. Material and methods: One hundred twelve patients with APS were included in the study, 57 of them with primary APS and 55 with coexisting SLE. HRQoL was measured by the 36-Item SF-36 and WHOQoL questionnaires. Results: Mean age was 47 years (47.6 ±13.8), and 96 patients were (85.7%) women. The mean disease duration was 72 months. Health-related quality of life impairment was found in both components for all APS patients in comparison to the healthy Polish population (p < 0.0001). There was no difference between APS and APS/SLE groups in HRQoL (mental component p = 1.0, physical component p = 0.337). The history of venous thrombosis was associated with HRQoL impairment only in the APS/SLE group in the physical component (p = 0.0118), not in primary APS (p = 0.6862). The mental component of SF-36 was associated with all domains of WHOQoL-BREF, while the physical component was associated only with physical health (p < 0.001). Conclusions: Primary APS and APS secondary to SLE lead to equal impairment in HRQoL. Diagnosis and proper management of all patients with APS are essential to prevent thrombosis and miscarriages, which ultimately will lead to longer survival with optimal life quality.

Are SMAD2/4/7 genetic variants associated with rheumatoid arthritis susceptibility and severity?

OBJECTIVES: SMADs play one of the key roles in the TGFß signalling pathway. Therefore, through their involvement in the immune response as well as in the fibrosis process, these proteins appear to take on one of the essential functions in the pathogenesis of autoimmune connective tissue diseases such as RA. This study aimed to investigate the association of selected SNPs in SMAD2/4/7 with RA risk in the Caucasian population and disease course in RA patients. METHODS: The study was conducted on 647 patients with established RA and 496 unrelated healthy controls (HCs). All patients fulfilled the American College of Rheumatology Diagnostic classification criteria for RA (ACR 1987). The analysis has been conducted using TaqMan genotyping assay. Transcript-inferred pathogenicity score (TraP-score) has been evaluated by TrapScore. PredictSNP.2 has been used to predict the effect of amino acid substitutions. RESULTS: The present study revealed in SMAD4 a significantly higher frequency of AG rs12456284 (under codominant model OR=0.62 p=0.027 and overdominant model OR=0.59 p=0.016) and GA rs10502913 (under codominant model OR=0.65 p=0.050 and overdominant OR=0.64 p=0.033) genotypes in healthy subjects in comparison to RA patients. Additionally, very strong LD has been noted between these two genetic variants (D'=0.95 r2=0.90). Moreover, bioinformatic analysis classified rs12456284 as deleterious change with 94% prediction accuracy. SMAD2 rs1792666 and SMAD7 rs3736242 showed to have the highest association with disease course. SMAD4 rs10502913, SMAD7 rs3736242, and SMAD7 rs4464148 were associated with the concentration of creatinine. CONCLUSIONS: Our results suggested that rs12456284 and rs10502913 in SMAD4 may have a potential protective effect against RA. Particularly, SMAD2 rs1792666 and SMAD7 rs3736242 seem to be significantly associated with diseases course in RA patients in the Caucasian population.

ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

Immunopathogenesis and Novel Therapeutics Strategies of Systemic Lupus Erythematosus.

Systemic lupus erythematosus is a chronic connective tissue disease of unknown origin and unpredictable course [...].

Mixed Connective Tissue Disease as Different Entity: Global Methylation Aspect.

Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.

IL-1ß, IL-10 and TNF-α polymorphisms may affect systemic lupus erythematosus risk and phenotype.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease, and IL-1ß, IL-10, and TNF-α genes are important in the pathogenesis of this disease. We studied the impact of IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, TNF-α -308, TNF-α -238, and TNF-α +489 polymorphisms on SLE risk and phenotype in SLE patients and healthy controls. METHODS: We genotyped SLE patients and healthy controls by real-time PCR on QuantStudio 5 (Applied Biosystems) and measured levels of cytokines by enzyme-linked immunosorbent assay (ELISA). RESULTS: We indicated that TNF-α -308, IL-10 -592, IL-10 -1082, IL-1ß-511 and IL-1ß +3953 polymorphisms affect SLE risk. Furthermore, we exposed that some of the TNF-α +489, TNF-α -238, IL-10 -1082 and IL-1ß +3953 genotypes are connected with the SLE phenotype. Moreover, we discovered the linking between specific genotypes and the serum concentrations of TNF-α, IL-1ß, and IL-10. CONCLUSIONS: In conclusion, our study revealed that IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, and TNF-α -308 polymorphisms may affect SLE risk and phenotype.

Impact of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Rheumatic Disease Patients on T Helper Cell Differentiation.

Complex pathogenesis of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is associated with an imbalance of various Th-cell subpopulations. Mesenchymal stem cells (MSCs) have the ability to restore this balance. However, bone marrow-derived MSCs of SLE and SSc patients exhibit many abnormalities, whereas the properties of adipose derived mesenchymal stem cells (ASCS) are much less known. Therefore, we examined the effect of ASCs obtained from SLE (SLE/ASCs) and SSc (SSc/ASCs) patients on Th subset differentiation, using cells from healthy donors (HD/ASCs) as controls. ASCs were co-cultured with activated CD4+ T cells or peripheral blood mononuclear cells. Expression of transcription factors defining Th1, Th2, Th17, and regulatory T cell (Tregs) subsets, i.e., T-bet, GATA3, RORc, and FoxP3, were analysed by quantitative RT-PCR, the concentrations of subset-specific cytokines were measured by ELISA, and Tregs formation by flow cytometry. Compared with HD/ASCs, SLE/ASCs and especially SSc/ASCs triggered Th differentiation which was disturbed at the transcription levels of genes encoding Th1- and Tregs-related transcription factors. However, we failed to find functional consequences of this abnormality, because all tested ASCs similarly switched differentiation from Th1 to Th2 direction with accompanying IFNγ/IL-4 ratio decrease, up-regulated Th17 formation and IL-17 secretion, and up-regulated classical Tregs generation.

Serum microRNAs in Systemic Sclerosis, Associations with Digital Vasculopathy and Lung Involvement.

Background and aims: Systemic sclerosis (SSc) is an autoimmune, rare multisystem chronic disease that is still not well-understood aetiologically and is challenging diagnostically. In the literature, there are ever-increasing assumptions regarding the epigenetic mechanisms involved in SSc development; one of them is circulating microRNAs. Many of them regulate TLR pathways and are significant in autoimmune balance. The aim of this study was to determine profile expression of selected microRNAs in SSc patients, including miR-126, -132, -143, -145, -155, -181a, -29a and -3148, in comparison to healthy controls. Methods: Serum microRNAs were isolated from 45 patients with SSc and 57 healthy donors (HC). Additionally, SSc patients were considered in the aspect of disease subtype, including diffuse systemic sclerosis (dcSSc) and limited systemic sclerosis (lcSSc). Results: miR-3148 was detected neither in the serum of HC nor in SSc patients. All of the rest of the analyzed microRNAs, excluding miR-126, miR-29a and miR-181a, were significantly upregulated in SSc patients in comparison to HC. However, miR-181a has been revealed only in the serum of patients with lcSSc but not dcSSc. Moderate positive correlations between the transfer factor of the lung for carbon monoxide (TLCO) and miR-126 and miR-145 were observed. A significant correlation has been found between serum miR-143 level and forced vital capacity (FVC). SSc patients with FVC ≤ 70% were characterized by significantly lower levels of miR-143 compared to patients with normal FVC. Additionally, the expression of miR-132 was significantly higher in dcSSc subgroup with detected active lung lesions compared to dcSSc patients with fibrotic lesions. Patients with an early scleroderma pattern of microangiopathy seen on nailfold video-capillaroscopy (NVC) revealed higher expression of miR-155 in serum than those with a late pattern. Conclusions: The expression profile of circulating cell-free miRNAs is significantly changed in the serum of SSc patients compared to healthy individuals. Downregulation of miRNA-181a and overexpression of miR-132, miR-143, miR-145 and miR-155 in serum may be significant in SSc in the context of biomarkers.

Global miRNA and mRNA expression profiles identify miRNA-26a-2-3p-dependent repression of IFN signature in systemic sclerosis human monocytes.

Dysregulation in type I IFN and IFN-stimulated genes (ISGs) induced by monocytes is one of the key features of systemic sclerosis (SSc) pathogenesis. Abnormalities in microRNA (miRNA) expression are related to excessive IFN production, however the role of miRNA remains largely elusive in SSc monocytes. This study explores global miRNA-mRNA profiling of SSc monocytes and functional attenuation of IFN and ISGs by specific miRNAs. Global sequencing of mRNA (mRNA-seq) and miRNA (miRNA-seq) samples were performed simultaneously on healthy controls and SSc monocytes. Following computational analysis, selected miRNAs-mRNA candidates were validated, correlated with clinical parameters, and tested by functional assays. Transcriptomics data and qPCR analysis confirmed IFN signature in SSc but not in rheumatoid arthritis monocytes. Based on miRNA-seq analysis, five miRNAs were selected for further validation. Only the expression patterns of miRNA-26a-2-3p and miRNA-485-3p were confirmed and negatively correlated with clinical parameters. Exogenous delivery of miRNA-26a-2-3p to TLR-stimulated monocytic THP-1 cells specifically inhibited ISGs but not inflammasome activity in functional assays. In conclusion, our miRNA-mRNA co-sequencing and functional analysis identify miRNA-26a-2-3p as a new candidate, which is predicated to negatively regulate ISGs. This implies that reduced expression of miRNA-26a-2-3 may be involved in pathogenic IFN signature in SSc monocytes.

Tissue factor and human apolipoprotein H genetic variants and pro-inflammatory cytokines in systemic lupus erythematosus patients.

OBJECTIVES: Tissue factor (TF) and Human apolipoprotein H (APOH) seem to be significantly associated with a clinical manifestation in systemic lupus erythematosus (SLE) patients with or without APS, mostly because of thrombotic events and coagulation processes. Additionally, according to recent studies, these two factors appear to be an important part of immune response and inflammation. METHODS: The objective of this study was to investigate three SNPs of APOH (rs4581, rs8178835 and rs818819) and three of TF (rs958587, rs3917615, rs1361600) in SLE patients and healthy subjects using TaqMan genotyping assay and their association with inflammatory cytokines level in serum and selected clinical parameters. RESULTS: Present study revealed that TF rs3917615 and rs958587 and APOH rs4581 possibly predispose to joint involvement in SLE. CONCLUSIONS: Analysed genetic variants of TF and APOH may have an impact on inflammatory processes and clinical relevance in SLE patients in the Caucasian population.

An Overview of Neonatal Lupus with Anti-Ro Characteristics.

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.

The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Microvascular damage - a marker of specific organ involvement in mixed connective tissue disease?

Mixed connective tissue disease (MCTD) is a complex entity, which incorporates features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). Nailfold videocapillaroscopy (NVC) is a simple, safe and non-invasive technique of capillary vessel assessment, allowing for qualitative and quantitative assessment of microcirculation. NVC plays a pivotal role in the diagnostic algorithm of connective tissue diseases, especially in systemic sclerosis (SSc). Numerous studies have shown a correlation between organ involvement and disease progression in SSc. In the current literature, there are limited data on relationship between NVC and organ involvement in MCTD patients. In the present article the relevant literature describing NVC examination in patients with MCTD and comparisons with some clinical situations are discussed.

Is intra-articular infliximab therapy a good alternative to radionuclide synovectomy for a patient with refractory pigmented villonodular synovitis?

Pigmented villonodular synovitis (PVNS) is a rare disease that has clinical and histopathological characteristics of both benign proliferative disorder and a chronic inflammatory process of the synovial tissue. The primary mode of treatment is surgery followed by an adjuvant radiotherapy; however, the risk of recurrence is a significant (40-70%). Several publications suggest that the TNF-α inhibitors might be a treatment option. We present a case of a 29-year-old female diagnosed with PVNS of the knee joint, refractory to surgery and 3 radionuclide synovectomies. Because the possibilities of conventional therapy were exhausted, treatment with an intra-articular anti-TNF-α monoclonal antibody (infliximab) was performed. Despite a high safety profile and a good tolerance of that therapy we did not observe significant clinical and radiological improvement. To assess the effectiveness of intra-articular TNF-α inhibitors as an adjuvant treatment in PVNS, prospective studies are needed.

Is the T-G-CT-G SNRNP70 haplotype another proof that mixed connective tissue disease is distinct from systemic lupus erythematosus and systemic sclerosis? A novel gene variant in SNRNP70 gene.

OBJECTIVES: U1-70K, encoded by the SNRNP70 gene, is a key early immunogen in connective tissue disease. The aim of the study was the genetic analysis of the SNRNP70 gene in mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients. METHODS: SNRNP70 genetic variants were detected using 3730 DNA Analyzer. SNRNP70 rs560811128 G/A (c.476-252 G/A), rs78616533delCT (c.475+130_475+131delCT) and rs117167710 T/C (c.393+326 T/C) variants were genotyped using the technique of sequence-specific hybridisation probe binding assays. SNRNP70 393_47 G/A mutation was detected using TaqMan SNP genotyping assay. RESULTS: We found one novel c.393+47G>A and three, c.476-252 G/A, c.475+130_475+131delCT and c.393+326 T/C, previously recorded variants. The present study revealed that T-G-CT-G haplotype demonstrated significantly higher frequencies in MCTD patients than in SLE and SSc patients. In MCTD patients c.475+130_475+131delCT distribution of genotype was gender-dependent and showed association with thrombo-/leukocytopenia. Mutation at position c.476-252G>A was predicted to possibly have an impact on splicing of the SNRNP70 transcript and it was present only in one MCTD patient. CONCLUSIONS: Our results demonstrated that the T-G-CT-G SNRNP70 haplotype is another proof that MCTD may be distinct from SLE and SSc. The novel c.476-252G>A mutation in SNRNP70 gene created a new acceptor splice site and may potentially alert of splicing of the SNRNP70 transcript.

IL-6 and TGF-ß gene polymorphisms, their serum levels, as well as HLA profile, in patients with systemic lupus erythematosus.

OBJECTIVES: The aim of the study was to explore whether TGF-ß and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients. METHODS: 216 SLE patients and 552 healthy individuals were examined for TGF-ß rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method. RESULTS: An increased frequency of TT genotype and T allele of the TGF ß -509 C/T was found in SLE patients (p=0.02). The TGF-ß 869 C allele was more frequent in SLE patients. The genotype-phenotype analysis showed association between the TGF ß -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- ß 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-ß and IL-6 serum level were found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-ß -509 TT genotype have shown positive association with the TGF-ß serum levels. Polish SLE patients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-ß serum levels in the Polish population. CONCLUSIONS: Our results suggested that the TGF ß -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.

Factors associated with quality of life in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. METHODS: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud's symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. RESULTS: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (ß = 2.854, p < 0.001) and anxiety (ß = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. CONCLUSIONS: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc.