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Article ; Online: miRNAs as Biomarkers and Possible Therapeutic Strategies in Rheumatoid Arthritis.

Kmiołek, Tomasz / Paradowska-Gorycka, Agnieszka

2022 Volume 11, Issue 3

Abstract: Within the past years, more and more attention has been devoted to the epigenetic dysregulation that provides an additional window for understanding the possible mechanisms involved in the pathogenesis of autoimmune rheumatic diseases. Rheumatoid ... ...

Abstract	Within the past years, more and more attention has been devoted to the epigenetic dysregulation that provides an additional window for understanding the possible mechanisms involved in the pathogenesis of autoimmune rheumatic diseases. Rheumatoid arthritis (RA) is a heterogeneous disease where a specific immunologic and genetic/epigenetic background is responsible for disease manifestations and course. In this field, microRNAs (miRNA; miR) are being identified as key regulators of immune cell development and function. The identification of disease-associated miRNAs will introduce us to the post-genomic era, providing the real probability of manipulating the genetic impact of autoimmune diseases. Thereby, different miRNAs may be good candidates for biomarkers in disease diagnosis, prognosis, treatment and other clinical applications. Here, we outline not only the role of miRNAs in immune and inflammatory responses in RA, but also present miRNAs as diagnostic/prognostic biomarkers. Research into miRNAs is still in its infancy; however, investigation into these novel biomarkers could progress the use of personalized medicine in RA treatment. Finally, we discussed the possibility of miRNA-based therapy in RA patients, which holds promise, given major advances in the therapy of patients with inflammatory arthritis.
MeSH term(s)	Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/therapy ; Autoimmune Diseases ; Biomarkers ; Humans ; MicroRNAs/genetics ; MicroRNAs/therapeutic use
Chemical Substances	Biomarkers ; MicroRNAs
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11030452
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pharmacogenomics of Anti-TNF Treatment Response Marks a New Era of Tailored Rheumatoid Arthritis Therapy.

Wysocki, Tomasz / Paradowska-Gorycka, Agnieszka

International journal of molecular sciences

2022 Volume 23, Issue 4

Abstract: Rheumatoid arthritis (RA) is the most commonly occurring chronic inflammatory arthritis, the exact mechanism of which is not fully understood. Tumor Necrosis Factor (TNF)-targeting drugs has been shown to exert high effectiveness for RA, which indicates ... ...

Abstract	Rheumatoid arthritis (RA) is the most commonly occurring chronic inflammatory arthritis, the exact mechanism of which is not fully understood. Tumor Necrosis Factor (TNF)-targeting drugs has been shown to exert high effectiveness for RA, which indicates the key importance of this cytokine in this disease. Nevertheless, the response to TNF inhibitors varies, and approximately one third of RA patients are non-responders, which is explained by the influence of genetic factors. Knowledge in the field of pharmacogenomics of anti-TNF drugs is growing, but has not been applied in the clinical practice so far. Different genome-wide association studies identified a few single nucleotide polymorphisms associated with anti-TNF treatment response, which largely map genes involved in T cell function. Studies of the gene expression profile of RA patients have also indicated specific gene signatures that may be useful to develop novel prognostic tools. In this article, we discuss the significance of TNF in RA and present the current knowledge in pharmacogenomics related to anti-TNF treatment response.
MeSH term(s)	Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/metabolism ; Genome-Wide Association Study/methods ; Humans ; Pharmacogenetics/methods ; Polymorphism, Single Nucleotide/genetics ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23042366
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Article ; Online: Cell Cultures as a Versatile Tool in the Research and Treatment of Autoimmune Connective Tissue Diseases.

Ejma-Multański, Adam / Wajda, Anna / Paradowska-Gorycka, Agnieszka

Cells

2023 Volume 12, Issue 20

Abstract: Cell cultures are an important part of the research and treatment of autoimmune connective tissue diseases. By culturing the various cell types involved in ACTDs, researchers are able to broaden the knowledge about these diseases that, in the near future, ...

Abstract	Cell cultures are an important part of the research and treatment of autoimmune connective tissue diseases. By culturing the various cell types involved in ACTDs, researchers are able to broaden the knowledge about these diseases that, in the near future, may lead to finding cures. Fibroblast cultures and chondrocyte cultures allow scientists to study the behavior, physiology and intracellular interactions of these cells. This helps in understanding the underlying mechanisms of ACTDs, including inflammation, immune dysregulation and tissue damage. Through the analysis of gene expression patterns, surface proteins and cytokine profiles in peripheral blood mononuclear cell cultures and endothelial cell cultures researchers can identify potential biomarkers that can help in diagnosing, monitoring disease activity and predicting patient's response to treatment. Moreover, cell culturing of mesenchymal stem cells and skin modelling in ACTD research and treatment help to evaluate the effects of potential drugs or therapeutics on specific cell types relevant to the disease. Culturing cells in 3D allows us to assess safety, efficacy and the mechanisms of action, thereby aiding in the screening of potential drug candidates and the development of novel therapies. Nowadays, personalized medicine is increasingly mentioned as a future way of dealing with complex diseases such as ACTD. By culturing cells from individual patients and studying patient-specific cells, researchers can gain insights into the unique characteristics of the patient's disease, identify personalized treatment targets, and develop tailored therapeutic strategies for better outcomes. Cell culturing can help in the evaluation of the effects of these therapies on patient-specific cell populations, as well as in predicting overall treatment response. By analyzing changes in response or behavior of patient-derived cells to a treatment, researchers can assess the response effectiveness to specific therapies, thus enabling more informed treatment decisions. This literature review was created as a form of guidance for researchers and clinicians, and it was written with the use of the NCBI database.
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; Autoimmune Diseases/therapy ; Connective Tissue Diseases/drug therapy ; Inflammation ; Cell Culture Techniques
Language	English
Publishing date	2023-10-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12202489
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Article: How the gut microbiota contributes to changes of autoimmune phenotype - from molecular studies to clinical utility.

Paradowska-Gorycka, Agnieszka / Wajda, Anna

Reumatologia

2020 Volume 58, Issue 4, Page(s) 189–190

Language	English
Publishing date	2020-08-31
Publishing country	Poland
Document type	Editorial
ZDB-ID	604151-6
ISSN	0034-6233
ISSN	0034-6233
DOI	10.5114/reum.2020.98427
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Article: Application of NGS Technology in Understanding the Pathology of Autoimmune Diseases.

Wajda, Anna / Sivitskaya, Larysa / Paradowska-Gorycka, Agnieszka

Journal of clinical medicine

2021 Volume 10, Issue 15

Abstract: NGS technologies have transformed clinical diagnostics and broadly used from neonatal emergencies to adult conditions where the diagnosis cannot be made based on clinical symptoms. Autoimmune diseases reveal complicate molecular background and ... ...

Abstract	NGS technologies have transformed clinical diagnostics and broadly used from neonatal emergencies to adult conditions where the diagnosis cannot be made based on clinical symptoms. Autoimmune diseases reveal complicate molecular background and traditional methods could not fully capture them. Certainly, NGS technologies meet the needs of modern exploratory research, diagnostic and pharmacotherapy. Therefore, the main purpose of this review was to briefly present the application of NGS technology used in recent years in the understanding of autoimmune diseases paying particular attention to autoimmune connective tissue diseases. The main issues are presented in four parts: (a) panels, whole-genome and -exome sequencing (WGS and WES) in diagnostic, (b) Human leukocyte antigens (HLA) as a diagnostic tool, (c) RNAseq, (d) microRNA and (f) microbiome. Although all these areas of research are extensive, it seems that epigenetic impact on the development of systemic autoimmune diseases will set trends for future studies on this area.
Language	English
Publishing date	2021-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10153334
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Article ; Online: Epigenetic Regulations of AhR in the Aspect of Immunomodulation.

Wajda, Anna / Łapczuk-Romańska, Joanna / Paradowska-Gorycka, Agnieszka

International journal of molecular sciences

2020 Volume 21, Issue 17

Abstract: Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and ... ...

Abstract	Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review sheds the light on the common ground between remodeling chromatin compounds and autoimmune antibodies used in diagnostics. In the proposed review we summarize recent findings that describe epigenetic factors which regulate AhR activity and impact diverse immunological responses and pathological changes.
MeSH term(s)	Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/metabolism ; Autoimmune Diseases/pathology ; Autoimmunity/immunology ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Immunomodulation ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism
Chemical Substances	Receptors, Aryl Hydrocarbon
Keywords	covid19
Language	English
Publishing date	2020-09-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21176404
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Article ; Online: Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis-From Research to Clinical Practice.

Wysocki, Tomasz / Olesińska, Marzena / Paradowska-Gorycka, Agnieszka

Cells

2020 Volume 9, Issue 5

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenic mechanism. However, it has been proven that the key underlying risk factor is a genetic predisposition. Association studies of the HLA-DRB1 gene clearly indicate its importance ...

Abstract	Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenic mechanism. However, it has been proven that the key underlying risk factor is a genetic predisposition. Association studies of the HLA-DRB1 gene clearly indicate its importance in RA morbidity. This review presents the current state of knowledge on the impact of HLA-DRB1 gene, functioning both as a component of the patient's genome and as an environmental risk factor. The impact of known HLA-DRB1 risk variants on the specific structure of the polymorphic HLA-DR molecule, and epitope binding affinity, is presented. The issues of the potential influence of HLA-DRB1 on the occurrence of non-articular disease manifestations and response to treatment are also discussed. A deeper understanding of the role of the HLA-DRB1 gene is essential to explore the complex nature of RA, which is a result of multiple contributing factors, including genetic, epigenetic and environmental factors. It also creates new opportunities to develop modern and personalized forms of therapy.
MeSH term(s)	Anti-Citrullinated Protein Antibodies/immunology ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Epitopes/immunology ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics ; Humans ; Practice Patterns, Physicians'
Chemical Substances	Anti-Citrullinated Protein Antibodies ; Epitopes ; HLA-DRB1 Chains
Language	English
Publishing date	2020-05-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9051127
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Article: U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue diseasePart I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease.

Paradowska-Gorycka, Agnieszka

Reumatologia

2015 Volume 53, Issue 2, Page(s) 94–100

Abstract: Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It ...

Abstract	Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It is still controversial whether MCTD is a distinct clinical entity among systemic connective tissue diseases, although several authors consider that it is distinct and underline characteristic, distinct clinical, serological and immunogenetic features. The putative target of autoimmunity in MCTD is U1-RNP, which is a complex of U1-RNA and small nuclear RNP. Both the U1-RNA component and the specific proteins, particularly U1-70K, engage immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. U1-RNA is capable of inducing manifestations consistent with TLR activation. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.
Language	English
Publishing date	2015
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	604151-6
ISSN	0034-6233
ISSN	0034-6233
DOI	10.5114/reum.2015.51509
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Article: U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease.

Paradowska-Gorycka, Agnieszka

Reumatologia

2015 Volume 53, Issue 3, Page(s) 143–151

Abstract: Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP ... ...

Abstract	Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self-RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD.
Language	English
Publishing date	2015
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	604151-6
ISSN	0034-6233
ISSN	0034-6233
DOI	10.5114/reum.2015.53136
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Article ; Online: Predictors of treatment failure of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis with focus on haptoglobin, haptoglobin polymorphism and zonulin.

Chmielińska, Magdalena / Olesińska, Marzena / Felis-Giemza, Anna / Paradowska-Gorycka, Agnieszka / Palej, Karolina / Rejmer-Szcześniak, Julita / Szukiewicz, Dariusz

Rheumatology international

2023 Volume 44, Issue 3, Page(s) 483–495

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Spondylitis, Ankylosing/drug therapy ; Spondylitis, Ankylosing/genetics ; Spondylitis, Ankylosing/diagnosis ; Haptoglobins/genetics ; Haptoglobins/therapeutic use ; Sacroiliitis/diagnosis ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Spondylarthritis/diagnosis ; Treatment Failure ; Protein Precursors
Chemical Substances	zonulin ; Haptoglobins ; Anti-Inflammatory Agents, Non-Steroidal ; Protein Precursors
Language	English
Publishing date	2023-10-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8286-7
ISSN	1437-160X ; 0172-8172
ISSN (online)	1437-160X
ISSN	0172-8172
DOI	10.1007/s00296-023-05484-2
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