Effect of Abatacept Treatment on T Cells in Muscle Tissue and Peripheral Blood in Polymyositis and Dermatomyositis Patients

Quan Tang¹, Daniel Ramsköld², Olga Krystufkova³, Herman F Mann⁴, Cecilia Wick⁵, Maryam Dastmalchi⁶, Peter Brodin⁷, Vivianne Malmström⁸, Jiri Vencovsky⁹ and Ingrid E. Lundberg⁶, ¹Department of Medicine, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, ²Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Solna, Stockholm, Sweden, ³Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, ⁴1st Faculty of Medicine, Charles University, Prague, Prague, Czech Republic, ⁵Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, ⁶Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁷Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, ⁸Department of Medicine, Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, ⁹Pediatria II, Reumatologia, PRINTO, Istituto Giannina Gaslini, Genoa, Italy

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Abatacept, muscle biopsy and myositis, T cells

Session Information

Date: Sunday, November 13, 2016

Title: Muscle Biology, Myositis and Myopathies - Poster I: Basic/Translational

Session Type: ACR Poster Session A

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

Background/Purpose: Abatacept (CTLA4-Ig), a blocking agent for T cell co-stimulation, has been proven beneficial in several autoimmune diseases. The aim of the study was to measure local and systemic immune cell effects of abatacept in the context of polymyositis and dermatomyositis by comparing baseline with 6-month follow-up samples after abatacept treatment.

Methods: 14 patients were included in this substudy of a 6 months’ treatment delayed-start design trial. Abatacept was given as intravenous infusions 10mg/kg monthly, in total 7 times. Muscle biopsies and blood samples were taken at inclusion and 6 months of active therapy. Frozen biopsies from the two time points (n=6 patients) were sectioned and immunohistochemically stained for T cell, macrophage, and B cell markers. Conventional quantification and image analysis were used to calculate the expression of different markers in muscle tissue sections. Frozen PBMCs (n=13 patients) from baseline and 6 months treatment were analyzed with a 29-antibody panel by mass cytometry (CyTOF) focusing on T cell features. Citrus and t-test were used to analyze the CyTOF results.

Results: Following 6 months treatment, the expression ratio of FOXP3⁺/CD4⁺ in muscle sections increased significantly (P=0.03). For peripheral blood CyTOF data, 8 significant different clusters were identified by citrus analysis, which distinguished baseline from follow-up. The proportion of regulatory T cells (CD3e⁺CD4⁺CD25⁺FOXP3⁺) increased significantly (P=0.04) at follow-up. More specifically, the proportion of effector/memory like Tregs, CD3e⁺CD4⁺CD25⁺FOXP3⁺CCR6⁺CD5⁺ cells, increased significantly (P=0.01) while the other Treg subsets did not significantly change.

Conclusion: Our data from peripheral blood suggest that compared to other T cell subsets, regulatory T cells in IIM are relatively resistant to abatacept therapy. Amongst Tregs, the naïve subset were most sensitive. Similarly we observed an increase of Tregs also in affected muscle tissue which could allow more efficient muscle fiber regeneration/healing, implicating that abatacept may be a beneficial drug for myositis.

Disclosure: Q. Tang, None; D. Ramsköld, None; O. Krystufkova, None; H. F. Mann, None; C. Wick, None; M. Dastmalchi, None; P. Brodin, None; V. Malmström, None; J. Vencovsky, None; I. E. Lundberg, Bristol-Myers Squibb, 2,Bristol-Myers Squibb, 5,Idera, 5,AstraZeneca, 2,ATyr, 9.

To cite this abstract in AMA style:

Tang Q, Ramsköld D, Krystufkova O, Mann HF, Wick C, Dastmalchi M, Brodin P, Malmström V, Vencovsky J, Lundberg IE. Effect of Abatacept Treatment on T Cells in Muscle Tissue and Peripheral Blood in Polymyositis and Dermatomyositis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/effect-of-abatacept-treatment-on-t-cells-in-muscle-tissue-and-peripheral-blood-in-polymyositis-and-dermatomyositis-patients/. Accessed .

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