Corticosterois Therapy Restaured Treg/Th17 Balance in Patients with Polimyalgia Rheumatica

Lorena Alvarez-Rodriguez¹, Marcos Lopez-Hoyos², Jaime Calvo-Alen³, Elena Aurrecoechea⁴, Teresa Ruiz Jimeno⁴, Ignacio Villa⁴, Carmen Gonzalez-Vela⁵ and Victor M. Martinez-Taboada¹, ¹Rheumatology, Hospital Universitario Marques de Valdecilla. IFIMAV, Santander, Spain, ²Immunology, Hospital Universitario Marques de Valdecilla. IFIMAV, Santander, Spain, ³Rheumatology, Hospital de Sierrallana. Torrelavega. Spain, Torrelavega, Spain, ⁴Rheumatology, Hospital de Sierrallana, Torrelavega, Spain, ⁵Pathology Anatomy, Hospital Universitario Marques de Valdecilla. IFIMAV, Santander, Spain

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: corticosteroids, cytokines, polymyalgia rheumatica and regulatory cells

Session Information

Session Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: To characterize the levels of circulating T regulatory cells (Tregs) and Th17 cells in polymyalgia rheumatica (PMR).

Methods: The study included 46 patients with active untreated PMR and 12 age-matched healthy controls (HC). Thirty one PMR patients were also studied after disease control with corticosteroid (CS) therapy. As disease controls, 9 patients with giant cell arteritis (GCA) and 14 with elderly onset rheumatoid arthritis (EORA) were also included. Analysis of circulating regulatory T cells and TH17 cells were performed by flow cytometry. The suppressive capacity of peripheral Tregs was assessed by CFSE at a 1:1/Teffector ratio after polyclonal activation with anti-CD3 and anti-CD28.

Results: The frequency of CD4⁺CD25^hiFoxP3⁺CD127^{-/ low}CD27⁺ in the peripheral blood of active PMR was not significantly different from HC. However, patients with EORA showed marginally significant lower levels than HC (p=0.048) and GCA (p=0.048) patients. Therapy with CS showed no significant effect on the frequency of Tregs during the course of the disease. The frequency of CD4⁺IL17⁺IFN⁺ and CD8⁺CD28^–CD27⁺ cells was similar in all the study groups. The frequency of Th17 cells (CD4⁺IL17⁺IFN^– and CD4⁺IL17⁺CCR6⁺) was significantly higher in the peripheral blood of patients with PMR compared to HC (p=0.037) and decreased after disease control with CS therapy (p=0.031). No significant differences between PMR and the other disease controls were found. Consequently, the ratio Tregs/Th17 was significantly decreased in patients with active PMR (p=0.024) and restored to normal after disease control. Moreover, the suppressive capacity of Tregs was slightly increase in PMR patients compared to HC (p=0.047).

Conclusion: Active PMR is associated with increased frequency of Th17 cells that is corrected after CS therapy. The frequency of Tregs does not change in PMR. Thus, the onset of PMR seems to be associated with increased inflammatory cells with not counterbalance by regulatory cells.

Funding: ISCIII-FIS, IFIMAV

Disclosure:

L. Alvarez-Rodriguez,
None;

M. Lopez-Hoyos,
None;

J. Calvo-Alen,
None;

E. Aurrecoechea,
None;

T. Ruiz Jimeno,
None;

I. Villa,
None;

C. Gonzalez-Vela,
None;

V. M. Martinez-Taboada,
None.

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