Melanocortin Gene Expression in Lymphocytes of Polymyalgia Patients

NCT ID: NCT05681676

Last Updated: 2023-01-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 9 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-03-01
• Study Completion Date: 2022-12-01

Brief Summary

Polymyalgia rheumatica (PMR) is a systemic inflammatory disorder with unknown etiology and overlapping symptoms with giant cell arthritis and rheumatoid arthritis (RA). The proteomic profile of PMR patients remains uncharacterized and biomarker studies very limited. The primary aim of this study was to thoroughly investigate the lymphocyte expression of melanocortin receptors, and the serum proteome during glucocorticoid treatment of PMR with a focus on acute-phase reactions, the complement system, and pro-inflammatory cytokines.

Detailed Description

Polymyalgia rheumatica (PMR) is a prototypic systemic inflammatory disease with overlapping symptoms similar to late onset rheumatoid arthritis (RA), giant cell arthritis (GCA), and cancer [1]. The etiology of PMR remains largely unknown, but it has been suggested that an age-related decline in the adaptive immune system might play a role in an over-compensatory inflammatory innate immune response [2]. Some genes and polymorphisms involved in initiation and regulation of inflammation have been associated with PMR [3,4] and polymorphisms are more predominant in the Northern European than Mediterranean population [5]. PMR has been somewhat successfully treated with glucocorticoids (e.g. prednisone) for more than half a century [6]. Due to the lack of causative molecular knowledge about the driving factors of inflammatory activation, and lack of treatment alternatives, glucocorticoids are still applied as the first line treatment today [7]. Relapses are common during standard glucocorticoid treatment [8], and randomized trials have failed to provide new treatment options [9,10]. However, recent progress in GCA treatment [11] have paved the way for biological treatment of PMR.

Only few serological biomarkers have been associated to PMR pathogenesis and disease activity while the pathogenesis of RA has been more thoroughly investigated. Hence, there is an unmet need to elucidate the pathophysiology of PMR. In this pilot-study, we therefore explored the potential to identify new serological markers at disease onset, which could be responsive to glucocorticoid treatment, which could be linked to PMR pathology. We did this using state-of-the-art quantitative proteomics profiling to investigate serum proteins from PMR patients before and after treatment with glucocorticoids for three months. In addition, we compared these patients with DMARD naïve RA patients, and healthy controls for potential molecular similarities. Hence, we applied advanced, qPCR to investigate lymphocyte expression, and mass spectrometry (MS) to measure serum proteins, and compared the results with serum cytokines.

Conditions

Polymyalgia Rheumatica

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Interventions

Blood samples before and after standard of care of polymyalgia rheumatica

Blood samples were taken before glucocorticoid treatment and three months after.

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

• no cancer related findings on computed tomography (CT) of the abdomen, and chest X-ray to increase specificity as described by ACR 2012 classification criteria [22

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aalborg University

OTHER

Sponsor Role: lead

Responsible Party

Michael Kruse Meyer

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

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Other Identifiers

N-20120074

Identifier Type: -

Identifier Source: org_study_id