MicroRNAs in Axial Spondylarthritis: an Overview of the Recent Progresses in the Field with a Focus on Ankylosing Spondylitis and Psoriatic Arthritis

Abstract Purpose of Review To highlight the recent discoveries and lines of evidence on the role of microRNAs in ankylosing spondylitis (AS) and psoriatic arthritis (PsA), focusing on their expression profiling and mechanisms of action. Recent Findings AS and PsA are chronic inflammatory musculoskeletal diseases with axial manifestations and represent an excellent model for studying microRNAs contribution to the disease pathogenesis, particularly through immunomodulation, inflammation, and bone remodelling, or their value as candidate diagnostic and prognostic biomarkers. Summary MicroRNAs are single-stranded nucleotides able to regulate gene expression. They are a key component of the epigenetic machinery, involved in physiological and pathological processes. The contribution of microRNAs in AS and PsA (such as miR-29a in regulating bone metabolism) is highlighted by several works in the field but their utility as possible markers must be still confirmed, particularly in larger patients’ cohorts.

Download Full-text

Spondyloarthritis phenotypes: rationale of evaluation in context of personified medicine

Medical alphabet ◽

10.33667/2078-5631-2019-2-37(412)-16-21 ◽

2020 ◽

Vol 2 (37) ◽

pp. 16-21

Author(s):

A. R. Babaeva ◽

E. V. Kalinina ◽

M. S. Zvonorenko ◽

I. V. Kostriukova

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Clinical Manifestation ◽

Hla B27 ◽

Genetic Characteristics ◽

Clinical Presentations ◽

Gender And Age ◽

Structural Progression ◽

Axial Spondylarthritis

The article contents the analysis of different clinical phenotypes in the most common spondyloarthritis (SpA): ankylosing spondylitis (AS), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA). SpA polymorphism has been discussed on the basis of multiple clinical presentations, structural lesions, radiological, immunological and genetic characteristics. Role of pro-inflammatory agents especially IL-17 in structural progression has been pointed out. Recent data regarding the link between HLA-B27 antigen, gender and age specificity and different clinical manifestation of SpA are presented. Current algorithms for SpA management based on evidence of efficacy sDMARD and/or biologics in separate phenotypes of SpA as well as resistance to DMARD are highlighted. Authors have concluded that meticulous analysis of SpA manifestation and patient’s individual profile is critical in rational SpA management according to personified medicine strategy.

Download Full-text

Prediction of Cardiovascular Events in Patients with Ankylosing Spondylitis and Psoriatic Arthritis: Role of Lipoproteins in a High-risk Population

The Journal of Rheumatology ◽

10.3899/jrheum.111307 ◽

2012 ◽

Vol 39 (7) ◽

pp. 1433-1440 ◽

Cited By ~ 3

Author(s):

ANNE GRETE SEMB ◽

TORE K. KVIEN ◽

DAVID A. DeMICCO ◽

RANA FAYYAD ◽

CHUAN-CHUAN WUN ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Density Lipoprotein ◽

High Risk Population ◽

Proportional Hazard ◽

Mortality And Morbidity ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Increased Risk

Objective.To evaluate lipids and apolipoproteins as predictors of cardiovascular mortality and morbidity (CVD) in patients with spondyloarthritis (SpA).Methods.In the pooled cohort of participants in the IDEAL, TNT, and CARDS trials, 50 had ankylosing spondylitis (AS), 36 had psoriatic arthritis (PsA), and 21,641 did not have AS or PsA (non-SpA). We compared lipid levels at baseline between AS or PsA and non-SpA, and hazard ratios (HR) for CVD were calculated in a Cox proportional hazard model.Results.Atherogenic lipids were lower in samples from AS, but not in PsA, compared to non-SpA. The HR for 1 SD increase in baseline lipids for future CVD was for total cholesterol 1.39 (95% CI 0.82, 2.36) in AS, 1.01 (95% CI 0.44, 2.31) in PsA, and 1.10 (95% CI 1.07, 1.14) in non-SpA. Both high-density lipoprotein (HDL) and apolipoprotein (ApoA-1) were significantly associated with CVD in AS (HR 3.67, 95% CI 1.47, 9.06, and HR 1.89, 95% CI 1.02, 3.54, respectively), in contrast to PsA (HDL: HR 1.03, 95% CI 0.49, 2.15; ApoA-1: HR 0.79, 95% CI 0.34, 1.89) and non-SpA (HDL: HR 0.86, 95% CI 0.84, 0.89; ApoA-1: HR 0.88, 95% CI 0.85, 0.91).Conclusion.HDL and ApoA-1 were surprisingly associated with increased risk of future CVD in patients with AS, whereas these lipids were protective in non-SpA.

Download Full-text

Spondyloarthritis: management algorithms and experience of target therapy

Medical alphabet ◽

10.33667/2078-5631-2019-1-18(393)-6-12 ◽

2019 ◽

Vol 1 (18) ◽

pp. 6-12

Author(s):

A. R. Babaeva ◽

E. V. Kalinina ◽

M. S. Zvonorenko ◽

E. V. Shcherbinina ◽

I. V. Bramnik

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Target Therapy ◽

Current Data ◽

Interleukin 17 ◽

Basic Drug ◽

Insufficient Response ◽

Axial Spondylarthritis ◽

Management Algorithms

The article presents current data on algorithms for managing patients with the most common forms of spondylarthritis — ankylosing spondylitis, axial spondylarthritis and psoriatic arthritis, based on existing national and European recommendations. The analysis of innovative approaches to the patho‑genetic therapy of spondyloarthritis with special attention to the inhibition of interleukin‑17 using the drug secukinumab. Along with the literature data, there is a clinical experience of using secukinumab in patients with ankylosing spondylitis, axial spondyloarthritis, and psoriatic arthritis. It has been shown that secukinumab can improve the quality of treatment and achieve clinical remission in patients with high disease activity and adverse prognostic factors. In connection with the high efficacy and safety of treatment, the feasibility of using secukinumab as a first‑line biological agent with insufficient response to a standard basic drug is discussed.

Download Full-text

The role of secukinumab in the treatment of psoriatic arthritis and ankylosing spondylitis

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x18787766 ◽

2018 ◽

Vol 10 (9) ◽

pp. 169-180 ◽

Cited By ~ 9

Author(s):

Leticia Garcia-Montoya ◽

Helena Marzo-Ortega

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Inflammatory Diseases ◽

Outcome Data ◽

Term Outcome ◽

Treatment Protocols ◽

Long Term Outcome ◽

Significant Disability

Psoriatic arthritis and ankylosing spondylitis are chronic inflammatory diseases that can cause significant disability. The commercialization of the first tumour necrosis factor (TNF) inhibitors led to a radical improvement of the quality of life of people affected by these conditions; however, response was not universal, highlighting the need for alternative therapeutic targets. Secukinumab is a monoclonal interleukin (IL)-17A inhibitor which has been proven efficacious for psoriatic arthritis and ankylosing spondylitis in recent clinical trials. Dactylitis, enthesitis, skin and nails are some of the domains in which the inhibition of IL-17 has shown significant improvements apart from the joints. Its safety profile and satisfactory medium- to long-term outcome data are some of the aspects suggesting its potential impact in treatment protocols in the short term.

Download Full-text

PATHOPHYSIOLOGICAL MECHANISMS OF BALNEOTHERAPY WITH POTENTIAL IMPLICATIONS FOR CENTRAL ASIAN SPAS AND SANATORIUMS

Central Asian Journal of Medical Hypotheses and Ethics ◽

10.47316/cajmhe.2020.1.2.05 ◽

2021 ◽

Vol 1 (2) ◽

pp. 131-135

Author(s):

Sinan Kardeş ◽

Mine Karagülle

Keyword(s):

Mineral Water ◽

Clinical Symptoms ◽

Musculoskeletal Diseases ◽

Mechanisms Of Action ◽

Spa Therapy ◽

Physiological Mechanisms ◽

Central Asian ◽

Clinical Benefits ◽

And Oxidative Stress

Spa therapy includes all modalities/ treatments based on evidence that are administered in spas or sanatoriums. Balneotherapy, the immersion in mineral water, is the main balneological modality in spa therapy programs. Clinical trials performed in Europe, Turkey, and Israel have shown clinical benefits of spa therapy/ balneotherapy in several diseases mainly pertaining to rheumatic and musculoskeletal diseases and dermatological diseases as well. However, mechanisms by which balneotherapy may improve the clinical symptoms of patients have been less evaluated/ documented in the literature. Although the literature on mechanisms of action of balneotherapy has still been evolving and accumulating, some evidence from preliminary studies paves the way for generating a hypothesis that balneotherapy has an influence on physiological mechanisms, immune system, inflammation, and oxidative stress. Extrapolation of the evidence-based clinical practice and scientific experience of Europe, Turkey, and Israel to Central Asian spas and sanatoriums is although possible; future studies investigating clinical efficacy, safety profile, and possible mechanisms of action of balneotherapy of regional spas are needed to better understand the role of balneotherapy and whether it has any local differences.

Download Full-text

Therapy-related issues: musculoskeletal

10.1093/med/9780198735823.003.0024 ◽

2017 ◽

Author(s):

Philip Wiffen ◽

Marc Mitchell ◽

Melanie Snelling ◽

Nicola Stoner

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Musculoskeletal Diseases ◽

British National Formulary ◽

National Formulary ◽

Clinical Pharmacists

This chapter outlines information relevant to clinical pharmacists related to musculoskeletal diseases and is loosely based on the British National Formulary, Chapter 10. In particular, this chapter covers rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, osteoarthritis, osteoporosis, and gout.

Download Full-text

Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics

Mediators of Inflammation ◽

10.1155/2017/8909834 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 44

Author(s):

Fabrizio Cantini ◽

Carlotta Nannini ◽

Laura Niccoli ◽

Linda Petrone ◽

Giuseppe Ippolito ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Underdeveloped Countries ◽

Increased Risk ◽

Tuberculosis Reactivation ◽

Necrosis Factor

Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary.

Download Full-text

MicroRNA in Glioblastoma: An Overview

International Journal of Genomics ◽

10.1155/2017/7639084 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 39

Author(s):

Barbara Banelli ◽

Alessandra Forlani ◽

Giorgio Allemanni ◽

Anna Morabito ◽

Maria Pia Pistillo ◽

...

Keyword(s):

Noncoding Rna ◽

Multimodal Therapy ◽

Epigenetic Factors ◽

Predictors Of Outcome ◽

Regulate Gene Expression ◽

Rna Molecules ◽

Complementary Sequences ◽

Epigenetic Machinery ◽

Potential Applications

Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode. MicroRNAs (miRNA) are a class of ncRNA of about 22 bp that regulate gene expression by binding to complementary sequences in the mRNA and silence its translation into proteins. MicroRNAs reversibly regulate transcription through nonmutational mechanisms; accordingly, they can be considered as epigenetic effectors. In this review, we will discuss the role of miRNA in glioma focusing on their role in drug resistance and on their potential applications in the therapy of this tumor.

Download Full-text

Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis

RMD Open ◽

10.1136/rmdopen-2019-001042 ◽

2020 ◽

Vol 6 (1) ◽

pp. e001042 ◽

Cited By ~ 3

Author(s):

Alexis Ogdie ◽

Kurt de Vlam ◽

Iain B McInnes ◽

Philip J Mease ◽

Philip Baer ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Musculoskeletal Diseases ◽

Activity Index ◽

Short Form ◽

Bodily Pain ◽

Disease Diagnosis ◽

Phase Iii ◽

Inadequate Response

ObjectiveTo describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of randomised controlled trials.MethodsData were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient’s Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population.ResultsOverall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12.ConclusionTofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases.

Download Full-text

IL-23 Inhibition in Ankylosing Spondylitis: Where Did It Go Wrong?

Frontiers in Immunology ◽

10.3389/fimmu.2020.623874 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dominique Baeten ◽

Iannis E. Adamopoulos

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Therapeutic Efficacy ◽

Th17 Cells ◽

Axial Spondyloarthritis ◽

Chronic Arthritis ◽

Lessons Learned ◽

Clinical Therapeutics ◽

Prevalent Form

Axial spondyloarthritis is a prevalent form of chronic arthritis which is related to psoriatic arthritis and skin psoriasis. TNF and IL-17A as well as IL-17F are key cytokines contributing to the pathobiology of this disease, as evidence by the therapeutic efficacy of inhibition of these factors. Despite the evidence that IL-23 acts as an upstream driver of Th17 cells, the T lymphocytes producing IL-17, and that IL-23 inhibition shows profound efficacy in psoriasis, blocking IL-23 failed to show any evidence of clinical efficacy in axial spondyloarthritis. In this viewpoint article, we revisit the reasons-to-believe in a role of IL-23 in the pathobiology of axial spondyloarthritis, discuss what we have learned on the pathobiology of this disease in general and on the function of the IL-23/IL-17 axis in particular, and share a handful of lessons learned that are of relevance for the translation of emerging biological insights into clinical therapeutics.

Download Full-text