1548: Immune Cells Are Highly Disturbed in Polymyalgia Rheumatica Patients

Guillermo CARVAJAL ALEGRIA¹, Sara Boukhlal², Sophie Hillion³, Pierre Pochard³, Emmanuelle Porchet³, Alain Saraux⁴, sandrine jousse joulin⁵, Thierry MARHADOUR⁶, Dewi Guellec³, Divi CORNEC⁷ and Valerie Devauchelle², ¹CHRU de Tours, Tours, France, ²Université de Bretagne Occidentale, Brest, France, ³CHRU de Brest, Brest, France, ⁴CHU Brest, Brest, France, ⁵Roche, Brest, France, ⁶CHU Cavale Blanche, Brest, France, ⁷CHRU Brest, Brest, France

Background/Purpose: Polymyalgia rheumatica (PMR) is an inflammatory disease. But it's pathophysiology and the impact of the treatments on immune cells are poorly known. Our objectives were to describe the immune cells of patients with PMR dependent from glucocorticoids and to analyze their evolution under tocilizumab.

Methods: the SEMAPHORE trial (NCT02908217) was a randomized control trial including patients with PMR dependent from glucocorticoids. Between inclusion and week 12, patients were blindly treated with either tocilizumab infusion or placebo infusion every 4 weeks associated to a tapering of glucocorticoids. Age and sex-matched healthy controls (HC) were recruited in the rheumatology department of the Brest University Hospital. HC did not have any history or presence of cancer, auto-immune disease or active infection and did not received treatment with a known impact on the immune system. We analyzed immune cells on whole fresh blood after red cell lysis on flow cytometry (Navios, Cytoflex, Beckmann Coulter) after staining for CD16, CD56, CD19, CD14, CD4, CD8, CD3, CD45, IgD, IgM, CD21, CD27, CD24, CD38, CD5 CD126, CD62L, CD45RA, CD127, CD25, in four different panels.

Results: Samples were obtained for 40 PMR patients and 34 HC. At inclusion, in PMR patients, compared to HC, CD14+CD16- classical monocytes were increased (82±1% vs 77±2%, p=0.01), CD14-CD16+ non-classical monocytes were decreased (4±0.3% vs 7±0.6%, p< 0.0001), granulocytes were increased (63±2% vs 52±2%, p< 0.0001), natural killer cells were decreased (8±1% vs 13±1%, p=0.007). B cells were decreased (8±0.6% vs 10±0.8%, p=0.03), but with an enrichment in CD27-IgD- senescent B cells (p< 0.0001) and in CD21^low B cells (p=0.04). T cells were increased (70±2% vs 64±2%, p=0.02) with an enrichment in CD4+ T cells (p=0.02) and in CD4+CD25^highCD127- regulatory T cells (p< 0.0001). At week 12, in PMR patients receiving tocilizumab therapy, compared to PMR patients receiving placebo, granulocytes were lower (58±5% vs 73±2%, p=0.006) and monocytes were higher (8±1% vs 5±0.5%, p=0.02).

Conclusion: In patients with a PMR dependent from glucocorticoids, immune cells homeostasis is disturbed. Tocilizumab has an impact more pronounced on granulocytes and monocytes. Knowledge about immune disturbance in PMR might help to choose to use a targeted therapy when glucocorticoids are not sufficient.

Disclosures: G. CARVAJAL ALEGRIA, Roche-Chugai; S. Boukhlal, None; S. Hillion, None; P. Pochard, None; E. Porchet, None; A. Saraux, None; s. jousse joulin, None; T. MARHADOUR, None; D. Guellec, None; D. CORNEC, None; V. Devauchelle, Pfizer, Novartis, AbbVie/Abbott, Novartis, Bristol-Myers Squibb(BMS), Roche-Chugai, Galapados.