CTLA4-Ig (abatacept) therapy modulates T cell effector functions in autoantibody-positive rheumatoid arthritis patients

BMC Immunology

Vivianne Malmström²  Ronald van Vollenhoven¹  Khalid Muhammad²  Sukanya Raghavan²  Jessica Herrath²  Jennifer Pieper² 

[1] Unit for Clinical Therapy Research, Inflammatory Diseases, Karolinska Institute, Solna, Stockholm, Sweden;Rheumatology Unit, Department of Medicine at Karolinska University Hospital, Karolinska Institute, Solna, Stockholm, Sweden

关键词: ACPA;    Abatacept;    Regulatory T cells;    Cytokines;    T lymphocyte;    Autoimmunity;    Rheumatoid arthritis;   

Others  :  1077772
DOI  :  10.1186/1471-2172-14-34

 received in 2013-04-15, accepted in 2013-07-31,  发布年份 2013

【 摘 要 】

Background

Rheumatoid arthritis is a chronic inflammatory disease with a strong MHC class II component and where many patients develop characteristic autoantibodies towards the noncoding amino acid citrulline. Such anti-citrullinated protein antibodies (ACPA) have recently been put forward as an independent predictive factor for treatment response by co-stimulation blockade by CTLA4-Ig (abatacept). We have performed a mechanism of action study to dissect T cell functionality in RA patients with long-standing disease undergoing abatacept treatment and the influence of ACPA status.

Results

Peripheral blood samples were collected from RA patients as they started CTLA4-Ig treatment and 3 and 6 months later. A general decrease of regulatory T cell subsets was observed in the cohort. Additionally within the ACPA-positive group significant down-regulation of all key T cell effector subsets including Th1, Th2, and Th17 was observed by analyzing cytokines by intracellular flow cytometry and in cell culture supernatants.

RA synovial fluid samples were cultured in vitro in the presence or absence of CTLA4-Ig (abatacept). T cell cytokine production was diminished, but without increasing the functional capacity of CD4+CD25hi regulatory T cells as previously demonstrated in the context of TNF-blockade and anti-IL6R therapy.

Conclusions

Our immunological study of T cell functionality in RA patients, both ACPA-positive and ACPA-negative, starting biological therapy with the co-stimulation blockade abatacept (CTLA4-Ig) supports the recently published registry study implicating ACPA seropositivity as an independent predictive factor to treatment response as we observed the most striking effect on T cell subset modulation in ACPA-positive patients. These data further support the notion of RA as a disease with several sub-entities, where the ACPA-positive fraction represents a classical HLA-associated autoimmune disorder while ACPA-negative patients may have other driving forces apart from classical adaptive immune responses.

【 授权许可】

   
2013 Pieper et al.; licensee BioMed Central Ltd.

【 图 表 】

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