Analysis of Innate and Adaptive Immune Responses in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)

Jeremie Dion^1,2, Jonathan London^2,3, Benjamin Chaigne^2,4, Nicolas Dumoitier², Bertrand Dunogué⁵, Pascal Cohen³, Matthieu Groh⁴, Claire Le Jeunne⁴, Luc Mouthon^2,5 and Benjamin Terrier^2,5, ¹Internal medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ²INSERM U1016, Institut Cochin, Equipe Neutrophiles et Vascularites, Paris, France, ³Internal Medecine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ⁴National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ⁵Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: B cells, Churg-Strauss syndrome, pathogenesis and vasculitis, T cells

Session Information

Date: Monday, November 14, 2016

Title: Vasculitis - Poster II: ANCA-Associated Vasculitis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA, formerly called Churg-Strauss syndrome) belongs to ANCA-associated vasculitis and is characterized by late onset asthma, blood and tissue eosinophilia and systemic symptoms. Studies on pathophysiology of EGPA are scarce, explaining the lack of specific targeted therapy. In the present study, we analyzed the implication of innate and adaptive immunity in EGPA through a systematic phenotyping of T and B cells, type 2 innate lymphoid cell (ILC2) as well as cytokine profile in active and remission EGPA.

Methods: We included 15 patients with active EGPA, 8 patients in remission and 20 healthy controls (HC). B and T cells and type 2 innate lymphoid cells (ILC2) in peripheral blood were studied using flow cytometry. Cytokines and chemokines were assessed in sera from active EGPA (n=20), remission EGPA (n=25) and healthy controls (n=35), using Luminex® and ELISA.

Results: Compared to HC, overall EGPA patients had a significant increase of Th2 polarized (IL-4⁺) CD4⁺ T cells (3.6±3.8% vs. 1.1±1.3%, p=0.002) and a trend for increase of Th9 (IL-9⁺) cells (0.81±0.86% vs. 0.40±0.52%, p=0.1) and Th17 (IL-17⁺) CD4⁺ T cells (1.5±1.1% vs.0.9±0.5%, p=0.056), no differences were observed between active and remission patients in these groups. T follicular helpers (TFH) were increased in patients (7.3±3.1% vs 4.5±1.5%, p=0.001) whereas regulatory CD4 T cells were decreased (0.75±0.4% vs 1.5±0.8%, p=0.02). B cells from EGPA patients displayed an activated profile compared to HC with a significant increase of CD95 expression (56±13% vs 27±2%, p<0.0001), CD86 (28±14% vs 12±12%, p<0.001) and CD69 (11±11% vs 1.9±1.8%, p<0.0001). B cells inhibition markers expression, i.e. CD72 and CD22, was lower in EGPA than in controls (60±23% vs 81±8% for CD72, p<0.01, and 74±22% vs 87±9% for CD22, p<0.01). Circulating ILC2 were significantly decreased in EGPA patients compared to controls (317±336 vs 563±284 cells/ml, p<0.05) and in active EGPA compared to remission (143±53 vs 491±415 cells/ml, p<0.05). Regarding serum cytokine profile, levels of soluble ST2 (469 ± 268 vs 288±102 pg/ml, p=0.002), IL-25 (302±405 vs 107±99 pg/ml, p=0.04), TSLP (5.6±5.9 vs 1.4±1.3 pg/ml, p=0.001) and TARC/CCL17 (1143±710 vs 709±287 pg/ml, p=0.05) were increased in EGPA compared to controls. Th2 cytokines were also more elevated in EGPA than in HC, including IL-5 (2.8±6 vs 0.53±0.11 pg/ml, p<0.0001) and IL-9 (1.6±2 vs 0.58±0.2 pg/ml, p=0.03). Th1-related cytokine IFN-γ was also elevated (2.1±0.8 vs 1.6±0.2 pg/ml, p=0.02) as well as Th17-related cytokine IL-17 (10.2±22 vs 1.3±0.4 pg/ml, p=0.03). In contrast, no differences were noted for serum IL-33.

Conclusion: EGPA patients are characterized by a Th2 polarization of T cell response and a trend for Th9 and Th17 polarization in peripheral blood, an activation of B cells and a dramatic decrease of blood ILC2 during active disease. This decrease could be explained by a recruitment of these cells within involved tissues. Increase of IL-25, TSLP and TARC as well as Th2-related cytokines in serum could illustrate the cross-talk between innate and adaptive immunity in this disease, in which ILC2 could play a central role.

Disclosure: J. Dion, None; J. London, None; B. Chaigne, None; N. Dumoitier, None; B. Dunogué, None; P. Cohen, None; M. Groh, None; C. Le Jeunne, None; L. Mouthon, None; B. Terrier, None.

To cite this abstract in AMA style:

Dion J, London J, Chaigne B, Dumoitier N, Dunogué B, Cohen P, Groh M, Le Jeunne C, Mouthon L, Terrier B. Analysis of Innate and Adaptive Immune Responses in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/analysis-of-innate-and-adaptive-immune-responses-in-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss/. Accessed .

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