Melanocortin Gene Expression in Lymphocytes of Polymyalgia Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Is the Melanocortin System Involved in Inflammatory Resolution

Conditions
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Polymyalgia Rheumatica

Intervention / Treatment
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* Other: Blood samples before and after standard of care of polymyalgia rheumatica


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The PMR diagnosis fulfilled the ACR 1987 criteria [20]. Additional inclusion criteria were elevated CRP, and sedimentation rate, ultrasound verified synovitis [21], and ]. 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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Blood samples before and after standard of care of polymyalgia rheumatica|Blood samples were taken before glucocorticoid treatment and three months after.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Melanocortin receptor expression | Melanocortin receptor expression determined like previously: https://pubmed.ncbi.nlm.nih.gov/27434862/ | 3 months. | 
| Serum proteome | Mass spectrometry investigated serum proteome | 3 months. |