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1.
Cells ; 8(12)2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861245

RESUMO

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.

2.
J Clin Med ; 8(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766529

RESUMO

Mixed connective tissue disease (MCTD) is a rare complex autoimmune disease in which autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the type I interferons, IFN-γ and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with MCTD. 145 MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-α/-ß/-γ serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A/rs2069705A/rs2069718G haplotype were significantly associated with a predisposition for MCTD. Raynaud's phenomenon, erosive arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A autoantibodies most frequently occurred in MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic biomarkers for MCTD susceptibility and severity.

3.
Clin Exp Rheumatol ; 37 Suppl 119(4): 32-40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573470

RESUMO

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.


Assuntos
Lúpus Eritematoso Sistêmico , Doença Mista do Tecido Conjuntivo , Ribonucleoproteína Nuclear Pequena U1 , Escleroderma Sistêmico , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/genética , Doença Mista do Tecido Conjuntivo/genética , Ribonucleoproteína Nuclear Pequena U1/genética , Ribonucleoproteína Nuclear Pequena U1/imunologia , Escleroderma Sistêmico/genética , Tomografia Computadorizada por Raios X
4.
Qual Life Res ; 28(12): 3347-3354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31482431

RESUMO

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.

5.
Biomolecules ; 9(8)2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405022

RESUMO

We investigated kinase insert domain-containing receptor (KDR) polymorphisms and protein levels in relation to susceptibility to and severity of Rheumatoid Arthritis (RA). 641 RA patients and 340 controls (HC) were examined for the rs1870377 KDR variant by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method and for rs2305948 and rs2071559 KDR single nucleotide polymorphisms (SNPs) by TaqMan SNP genotyping assay. KDR serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The rs1870377 KDR variant has shown association with RA under the codominant (p = 0.02, OR = 1.76, 95% CI = 1.09-2.85) and recessive models (p = 0.019, OR = 1.53, 95% CI = 1.07-2.20). KDR rs2305948 was associated with RA under the dominant model (p = 0.005, OR = 1.38, 95% CI = 1.10-1.73). Under the codominant model, the frequency of the rs2071559 TC and GG genotypes were lower in RA patients than in controls (p < 0.001, OR = 0.51, 95% CI = 0.37-0.69, and p = 0.002, OR = 0.57, 95% CI = 0.39-0.81). KDR rs2071559 T and rs2305948 A alleles were associated with RA (p = 0.001, OR = 0.60, 95% CI = 0.45-0.81 and p = 0.008, OR = 1.71, CI = 1.15-2.54). KDR rs2305948SNP was associated with Disease Activity Score (DAS)-28 score (p < 0.001), Visual Analog Scale (VAS) score (p < 0.001), number of swollen joints (p < 0.001), mean value of CRP (p < 0.001). A higher KDR serum level was found in RA patients than in HC (8018 pg/mL versus 7381 pg/mL, p = 0.002). Present results shed light on the role of KDR genetic variants in the severity of RA.

6.
Reumatologia ; 57(3): 145-150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462829

RESUMO

Objectives: Inflammatory processes in rheumatic diseases spread via various types of immune system cells and tissues with the aid of inflammatory cytokines and growth factors and the participation of vascular endothelium. Research is still conducted to determine the role of individual factors in the pathophysiology of rheumatic diseases. The task is complicated because the multiplane network of cytokines is characterized by complex correlations manifesting as positive and negative feedback, which impedes the definitive interpretation of the role of specific cytokines. Therefore, it seems justified to perform a comparative analysis of the expression of at least several molecules in one study, which may help reveal their role in the pathogenesis of rheumatic diseases and have prognostic value. Material and methods: The aim of the study involves the assessment and comparative analysis of the concentrations of interleukin 35 (IL-35), tumour necrosis factor α (TNF-α), B-cell-activating factor (BAFF), and vascular endothelial growth factor (VEGF) in peripheral blood serum in patients with rheumatoid arthritis (RA) (n = 43), systemic lupus erythematosus (SLE) (n = 28), antiphospholipid syndrome (APS) (n = 24), and mixed connective tissue disease (MCTD) (n = 9). The main intention is to search for biomarkers for specific rheumatic diseases. Cytokine and growth factor levels were determined using specific ELISA kits. Results: Statistically significant differences in VEGF and IL-35 concentrations occurred between patients with APS vs. RA and SLE vs. RA. There was a significant high positive correlation between the concentration of BAFF and TNF-α (r = 0.77, p < 0.0000) in patients with APS, as well as in patients with SLE (r = 0.55, p = 0.00). Conclusions: BAFF and TNF-α may be promising biomarkers in patients with APS and VEGF in patients with RA. Additionally, IL-35 may be a useful marker for the diagnosis of APS. Positive correlation of BAFF and TNF-α concentrations in APS and SLE potentially indicates much more similar etiopathogenesis of these diseases than it could be previously predicted.

7.
Autoimmunity ; 52(3): 126-135, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31257985

RESUMO

Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Recent discoveries try to connect NETs formation with autoimmune diseases, like systemic lupus erythematosus (SLE) or granulomatosis with polyangiitis (GPA) and place them among one of the factors responsible for disease pathogenesis. The aim of the study was to assess the NETotic capabilities of neutrophils obtained from freshly diagnosed autoimmune patients versus healthy controls. Further investigation involved assessing NETs production among treated patients. In the latter step, NETs degradation potency of collected sera from non-treated patients was checked. Lastly, the polymorphisms of the DNASE I gene among tested subjects were checked. NETs formation was measured in a neutrophil culture by fluorometry, while degradation assessment was performed with patients' sera and extracellular source of DNA. Additionally, Sanger sequencing was used to check potential SNP mutations between patients. About 121 subjects were enrolled into this study, 54 of them with a diagnosed autoimmune disorder. Neutrophils stimulated with NETosis inducers were able to release NETs in all cases. We have found that disease affected patients produce NETs more rapidly and in larger quantities than control groups, with up to 82.5% more released. Most importantly, we showed a difference between the diseases themselves. NETs release was 68.5% higher in GPA samples when compared to SLE ones while stimulated with Calcium Ionophore. Serum nucleases were less effective at degrading NETs in both autoimmune diseases, with a reduction in degradation of 20.9% observed for GPA and 18.2% for SLE when compared with the controls. Potential therapies targeting neutrophils and NETs should be specifically tailored to the type of the disease. Since there are significant differences between NETs release and disease type, a standard neutrophil targeted therapy could prevent over-generation of traps in some cases, while in others it would deplete the cells, leaving the immune system unresponsive to primary infections.

8.
Clin Exp Rheumatol ; 37(6): 963-975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943147

RESUMO

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.


Assuntos
Interleucina-6 , Lúpus Eritematoso Sistêmico , Polimorfismo Genético , Fator de Crescimento Transformador beta , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Cadeias HLA-DRB1 , Humanos , Interleucina-6/sangue , Interleucina-6/genética , Lúpus Eritematoso Sistêmico/genética , Polônia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/genética
9.
Int J Rheum Dis ; 22(3): 386-391, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30548416

RESUMO

Co-occurrence of autoimmune diseases (ADs) within an individual is postulated to be a frequent phenomenon in rheumatic diseases. Similar clinical signs and symptoms, pathophysiological mechanisms, genetic factors within autoimmune diseases and aggregation of diverse ADs within families sustain the theory of shared pathogenesis of several ADs (autoimmune tautology). Polyautoimmunity (PA) is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). This analysis summarizes an estimated prevalence of PA in the most common rheumatic diseases, the presumable risk factors for PA and influence of concomitant diseases on the course of disease.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Doenças Reumáticas/imunologia , Animais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Autoimunidade/genética , Predisposição Genética para Doença , Humanos , Multimorbidade , Fenótipo , Prevalência , Prognóstico , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/genética , Medição de Risco , Fatores de Risco , Síndrome
10.
Reumatologia ; 56(5): 307-315, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30505013

RESUMO

Despite its misleading adjective, the most commonly used diagnostic criteria of idiopathic inflammatory myopathies (IIM) are applicable only after all other non-autoimmune muscle diseases have been excluded. It makes differential diagnosis the first step when approaching a patient with muscle weakness. This article is designed to list the most common conditions from which to differentiate in rheumatological care. In fact, many patients with the diseases described here have been initially misdiagnosed with IIM. For the purpose of this article, only the most commonly found and important conditions according to the authors are listed with the essence of information; other autoimmune muscle diseases, such as sarcoidosis and eosinophilic myositis, are not portrayed. The attached bibliography may serve as a source, when further exploration of a specific subject is needed.

11.
Reumatologia ; 56(4): 203-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30237624

RESUMO

Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The presented article discusses the mechanism of action and the clinical application of tofacitinib. Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with biological drugs already available.

12.
Med. clín (Ed. impr.) ; 151(5): 191-195, sept. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-173882

RESUMO

Introduction: Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population. Patients and methods: The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay. Results: The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant. Discussion: Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population


Introducción: La artritis reumatoide (AR) es una enfermedad autoinmune en la que las diferentes variantes genéticas en los genes de las citocinas pueden desempeñar un papel patogénico. Un GWAS de enfermedades autoinmunes destacó al gen IL-23R como uno de los factores de susceptibilidad. Examinamos tres polimorfismos de nucleótido único candidatos (SNP), rs10889677, rs11209026 y rs2201841 del gen IL-23R, y determinamos su posible asociación con AR en una población de Polonia. Pacientes y métodos: Se genotipificaron los polimorfismos del gen IL-23R en 422 pacientes de AR y 348 individuos sanos, utilizando la prueba TaqMan de genotipificación de SNP. Resultados: La frecuencia genotípica no se desvió de HWE en cada grupo examinado. La comparación del alelo, así como las frecuencias genotípicas de los polimorfismos de IL-23R con arreglo al modelo genético codomitante, dominante y recesivo no reveló diferencias significativas entre los pacientes de AR y los sujetos sanos. Demostramos también que rs2201841 y rs11209026 de IL-23R, al igual que rs11209026 y rs10889677, se hallaban en desequilibrio completo de ligamiento (D’ =1). Nuestro análisis genotipo-fenotipo demostró que en portadores del alelo rs10889677C y/o rs2201841A eran más frecuentes el FR, las manifestaciones extra-articulares y la erosión que en los pacientes portadores del alelo rs10889677A y/o rs2201841A, aunque esta asociación no fue significativa. Discusión: Los hallazgos presentes demostraron que las variantes genéticas asociadas a las enfermedades autoinmunes en el gen IL-23R no están asociadas a AR en la población polaca


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Artrite Reumatoide/genética , Citocinas/genética , Interleucina-23/análise , Artrite Reumatoide/patologia , Polimorfismo Genético , Polônia
13.
Reumatologia ; 56(3): 140-148, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042601

RESUMO

Objectives: Biologics are medications widely applied in the management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of Polish patients treated with biologics. Material and methods: An anonymous questionnaire was distributed in 23 Polish rheumatological centers involved in the treatment; 1212 returned questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18 years old). The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland. Results: A beneficial or very beneficial influence of the medication on the state of physical health was found mostly in patients with rheumatoid arthritis (51.3 and 30.5%) and ankylosing spondylitis (51.0 and 36.8%). Family life was improved by the treatment especially in patients with ankylosing spondylitis (40.7 and 35.6% beneficial and very beneficial, respectively), sleep quality and sexual life mostly in those with ankylosing spondylitis (beneficial/very beneficial influence 41.5/38.4, and 38.7/23.9, respectively). There was a rather small influence of biological treatment on the financial situation of the patients. In general, satisfaction with the treatment was evaluated as positive or very positive in 88% of all investigated patients.In a significant part of the patients, transportation to the medical center was considered as a disadvantage of the treatment. About one-third of the patients considered laboratory and imaging tests to be done before initiation of the medication as a difficulty, and for about 40% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients. Conclusions: Summing up, the results were similar in the patients suffering from various diseases although those with psoriatic arthritis felt the highest satisfaction (possibly due to the positive aesthetic effect), and those with ankylosing spondylitis had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with juvenile idiopathic arthritis. There was a small influence of medication on financial status of the patients. Application of biologics has few disadvantages and most of them are associated with the organization of health services (waiting time for the tests, transportation to the medical centers).

14.
Reumatologia ; 56(3): 164-173, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042604

RESUMO

Antimalarial drugs (AD) are a group of widespread therapeutic agents in multiple rheumatic indications. Although the effect of AD is mild and extended in time, low toxicity is their appreciated value. This paper describes the current state of knowledge on the mechanism of action, use, toxicity and pleiotropic effects of AD in the pharmacotherapy of autoimmune diseases.

15.
Reumatologia ; 56(2): 73-79, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29853721

RESUMO

Objectives: Rheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population. Material and methods: A total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis. Results: The distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05). Conclusions: We did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.

16.
Reumatologia ; 56(1): 45-54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29686443

RESUMO

Systemic lupus erythematosus (SLE) is multi-system autoimmune rheumatic disorder with very broad clinical picture. Due to its generalized nature it influences all aspects of patient's life: physical, psychological and social well-being. With the development in diagnosis and treatment of SLE, median survival increased significantly over the past years. This article focused on the elements of quality of life, which are especially important for SLE patients, like body image, fatigue, family relations, disease impact on professional and social life. The quality of life could be measured with two different instruments: generic and disease-specific questionnaires. Generic ones are used to assess the quality of life of patients comparing to general population whereas specific questionnaires are designed to measure outcomes in one specific disease. The aim of the article is to describe HRQoL in SLE patients and the variables important for patients which have impact on it.

17.
Inflamm Res ; 67(5): 423-433, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29411043

RESUMO

OBJECTIVES: The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA. METHODS: The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated. RESULTS: Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19-9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D' = 0.96 and r2 = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG. CONCLUSION: The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fator Reumatoide/metabolismo
18.
Med Clin (Barc) ; 151(5): 191-195, 2018 09 14.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29370888

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population. PATIENTS AND METHODS: The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay. RESULTS: The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant. DISCUSSION: Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population.


Assuntos
Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Interleucina/genética , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Heterozigoto , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polônia
19.
Reumatologia ; 56(6): 346-353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30647480

RESUMO

Objectives: Sjögren's syndrome (SS) is an autoimmune disease characterised by heterogeneous clinical presentation and presence of various autoantibodies - anti-SSA/Ro of diagnostic value, less specific anti-SSB/La and others. We searched for biomarker(s) and potential therapeutic target(s) of SS subsets that vary in their autoantibody profile. Material and methods: Eighty-one patients with SS (70 female and 11 male) and 38 healthy volunteers (28 female and 10 male) were included in the study. Patients were categorised according to absence (group 1) or presence of anti-SSA/Ro antibody which occurred either alone (group 2) or together with anti-SSB/La (group 3). Clinical evaluation was performed, and presence of autoantibodies and concentrations of cytokines relevant to SS pathogenesis, i.e. a proliferation inducing ligand (APRIL), B-lymphocyte activating factor (BAFF), interleukin (IL) 4, IL-10, interferon α (IFN-α) and thymic stromal lymphopoietin (TSLP), in sera were determined. Results: Frequency of autoantibodies other than anti-SSA/Ro and anti-SSB/La, the number of autoantibody specificities and anti-nuclear antibody titres were higher in group 2 and/or 3 than in group 1 of SS patients. Moreover, SS patients of groups 2 and 3 developed disease symptoms at younger age, and more often had positive Schirmer's test and skin lesions. In addition, serum concentrations of APRIL, but not other tested cytokines, were significantly higher in the patients of both groups 2 and 3 than those of group 1 and healthy volunteers. Conclusions: Sjögren's syndrome patients with signs of B-cell epitope spreading are characterised by early disease onset, more frequent xerophthalmia and skin involvement, and up-regulated serum APRIL level. We suggest that therapeutic neutralisation of APRIL may be beneficial for these patients.

20.
Arthritis Rheumatol ; 69(12): 2271-2282, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29106061

RESUMO

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.


Assuntos
Miosite/classificação , Miosite/diagnóstico , Guias de Prática Clínica como Assunto , Reumatologia/normas , Avaliação de Sintomas/normas , Adolescente , Adulto , Biópsia/normas , Criança , Consenso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Sensibilidade e Especificidade , Sociedades Médicas , Avaliação de Sintomas/métodos , Estados Unidos , Adulto Jovem
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