The role of muscle in the susceptibility and progression of axial Spondyloarthritis: The MyoSpA Study Protocol

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Abstract Background: Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background. Objectives: To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties. Methods: A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples. Discussion: The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets.

Patrícia Gomes-Alves
iBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal

Fernando M Pimentel-Santos
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Jaime Cunha Branco
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Daniel Sobral
UCIBIO, DCV, FCT-NOVA, Caparica, Portugal

Celso Vladimiro Cunha
Institute of Hygiene and Tropical Medicine, Universidade NOVA de Lisboa and Global Health and Tropical Diseases Research Centre Lisbon, Portugal

Tatiana Vassilevskaia
Institute of Hygiene and Tropical Medicine, Universidade NOVA de Lisboa and Global Health and Tropical Diseases Research Centre Lisbon, Portugal

Bruno Miguel Alexandre
iBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal

Julia Costa
ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Oeiras, Portugal

Alfonse T Masi
University of Illinois, College of Medicine at Peoria, USA

Kalyani Nair
Bradley University, Mechanical Engineering department, USA

Sofia Ramiro
Leiden University Medical Center, Leiden, The Netherlands

Alexandre Sepriano
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Antonio Galzerano
Champalimaud Centre for the Unknown, Lisbon, Portugal

Sérgio Fernandes de Almeida
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa

César S Mendes
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal

Vasco Mascarenhas
MSK imaging Unit (UIME), Imaging Center, Hospital da Luz, Lisbon, Portugal

Carolina Lage Crespo
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal

João Lagoas-Gomes
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Lúcia Domingues
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Instituto Politécnico de Setúbal, Escola Superior de Saúde de Setúbal, Setúbal, Portugal

Santiago Rodrigues-Manica
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Rita Pinheiro Torres
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Agna Neto
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisboa, Rheumatology Department, Portugal

Atlas Mashayekhi Sardoo
CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Institute of Hygiene and Tropical Medicine, Universidade NOVA de Lisboa and Global Health and Tropical Diseases Research Centre Lisbon, Portugal

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