Stereological Quantification of Immune-Competent Cells in Biopsies from Painful Achilles Tendons of Psoriatic Arthritis Patients with Ultrasonic Verified Enthesitis
The main objective is to describe the histological findings of psoriatic arthritis enthesitis, and to a) Characterize and b) Quantify the immune-competent cell presence in tendon specimens obtained from the entheseal site of the Achilles tendon using immunohistochemistry and a stereological technique for the quantification, and to compare these observations with a) Those in healthy Achilles tendons, and b) Those in mono-symptomatic chronic Achilles tendinopathy. Secondly, to examine whether the immune-competent cell types are associated with 3-months remission rate of Achilles tendon pain, or with baseline a) Ultrasonic findings of the Achilles tendon; b) Psoriatic arthritis disease activity; c) Risk factors of cardiovascular disease; and d) Biomarkers of systemic inflammation.
Tendon pathologies are a characteristic component of psoriatic arthritis (PsA), and are observed in 35 % to 50 % of PsA patients. The Achilles tendon is one of the most commonly affected sites. This manifestation is usually located at the bone-tendon interface at the calcaneus insertion, and as such referred to as insertional tendinopathy or enthesitis. The current treatment remains suboptimal. We hope to provide new insight into the cellular mechanisms underlying PsA tendon and enthesis pathologies.
Core elementary lesions of ultrasonic detected Achilles enthesitis include hypoechogenicity, increased thickness of the tendon insertion, calcifications, enthesophytes, erosions, and Doppler activity. In contrast to this typical PsA Achilles enthesitis presentation, in non-PsA patients with mono-symptomatic chronic Achilles tendinopathy who do not fulfill the diagnostic criteria for PsA or any other systemic inflammatory disease, Achilles tendon pain is normally located at the mid-portion of the tendon (non-insertional Achilles tendinopathy). Despite this difference in location of tendon pain, these tendon pathologies share several clinical characteristics, including pain, swelling, and impaired function, as well as overlapping ultrasonic findings such as increases in tendon thickness, hypoechoic regions, disrupted tendon fibers, and increased vascularity/hyperemia within the tendon measured by Doppler. Also, both conditions often cause great morbidity and loss of quality of life, and response only suboptimal to current intervention strategies. One of the main obstacles for the development of effective treatment methods is that the disease mechanisms remain poorly understood. Indeed, although PsA enthesitis has been attributed to an inflammatory autoimmune response, and non-PsA mono-symptomatic tendinopathy traditionally has been viewed as a non-inflammatory degenerative condition due to repetitive micro-traumas, limited data exist on the true pathophysiological mechanisms, cellular as well as non-cellular, underlying both of these conditions.
Intriguingly, our research group has recently shown that immune-competent cells are present in mono-symptomatic non-PsA chronic Achilles tendinopathy. In particularly, macrophages and endothelial cells were significantly more numerous in these tendons compared with normal control tendons. Macrophages have also been identified as the predominant infiltrating cell type adjacent to enthesis fibrocartilage in PsA enthesitis. Based on these observations a long with the growing evidence of mechanical stress contributing as a triggering factor of both conditions, it could be speculated that PsA and classic "over-use" mono-symptomatic tendon pathologies share several autoimmunohistological features. Therefore, to shed new light on these underlying disease mechanisms, an immunohistochemical study examining the presence and function of immune-competent cells in PsA tendon pathologies is highly needed.
Description of the cohort
From January 2017 through 2019, 30 psoriatic arthritis patients presenting with ultrasonic verified Achilles entesitis will be enrolled.
Data and biological material
Clinical measures: Height, weight, blood pressure, Psoriasis Area Severity Index, SPARCC Enthesitis Score, swollen joint count (66), tender point count, tender joint count (68), doctors global (VAS 0-100 mm), BASMI, and VISA-A.
Patient questionnaires: Patient global (VAS), patient fatigue (VAS), patient pain (VAS), HAQ, BASFI and BASDI.
Biological material: Blood, feces, and Achilles tendon tissue.
Collaborating researchers and departments
Department of Rheumatology, Odense University Hospital and University of Southern Denmark
- PhD Student Maja Skov Kragsnæs, MD
- Professor Torkell Ellingsen, MD, PhD
- Consultant Jens Kristian Pedersen, MD, PhD
Musculo-skeletal Statistics Unit, The Parker Institute and Department of Rheumatology and Copenhagen University Hospital and University of Southern Denmark
- Senior biostatistician Robin Christensen, Bs, MS, PhD
Diagnostic Centre, Silkeborg Regional Hospital and University of Southern Denmark
- Consultant Ulrich Fredberg, MD, PhD
Department of Rheumatology, Odense University Hospital
- Consultant Hans Christian Horn, MD
- Consultant Heidi Munk, MD, PhD
Diagnostic Centre, Silkeborg Regional Hospital, DK.
- Consultant Søren Geill Kjær, MD
Institute of Pathology, Aarhus University Hospital
- Anne Ringer Ellingsen, MD, PhD
Department of Clinical Medicine, Aarhus University Hospital
- Professor Jens Randel Nyengaard