Abatacept reduces Circulating Effector Memory T-Helper Cells in Patients with Primary Sjögren’s Syndrome

Gwenny Verstappen¹, Wayel H. Abdulahad², Petra M. Meiners³, Suzanne Arends⁴, Silvia Beijer-Liefers⁵, Arjan Vissink³, Frans G.M. Kroese⁴ and Hendrika Bootsma⁴, ¹Rheumatology & Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, ²Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, Netherlands, ³Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, ⁴Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, ⁵University Medical Center Groningen, University of Groningen, Groningen, Netherlands

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Sjogren's syndrome, T cells and abatacept

Session Information

Title: Sjogren's Syndrome I: Clinical Perspectives

Session Type: Abstract Submissions (ACR)

Background/Purpose

In an open-label proof of concept study, Abatacept has been identified as an effective and safe treatment modality in primary Sjögren’s syndrome (pSS). Abatacept is a fully human fusion molecule of IgG-Fc and CTLA-4 that modulates the costimulatory interaction between APCs and T-lymphocytes, thereby inhibiting full T-cell activation. Modifying T-helper (Th-) cell homeostasis may contribute to the therapeutic effect of Abatacept as Th-cell subset imbalances are involved in the emergence of autoimmune diseases. Therefore, the aim of this study was to assess Th-cell homeostasis in peripheral blood of pSS patients in response to Abatacept treatment.

Methods

Fifteen patients with pSS, diagnosed according to the revised American-European Concensus Group criteria, were treated with Abatacept on days 1, 15, 29 and every four weeks thereafter for five months (≈10 mg/kg of body weight i.v.). Absolute numbers and frequencies of circulating Th-cell subsets (CD3⁺CD4⁺) were examined in fresh blood samples by flow cytometry at baseline and 4, 12, 16, 24, 36 and 48 weeks after the first dose. Expression patterns of chemokine receptors CCR7 and CD45RO were used for distinction between naive, central memory, effector memory and terminally differentiated Th-cells. Generalized estimating equations (GEE) were used to analyze the presence of different subsets over time within subjects, viz. on treatment (week 0-24) and off treatment (week 24-48). Currently, the extent to which different subsets of effector memory Th-cells are affected by Abatacept is under investigation.

Results

On Abatacept treatment, numbers of peripheral blood CD4⁺ T-cells did not significantly differ from baseline values. However, absolute numbers and frequencies of total memory Th-cells decreased significantly over time on treatment (p=0.001 and p<0.001, resp.). This was mainly a result of a decrease in effector memory Th-cells. On treatment, both absolute numbers and frequencies of effector memory Th-cells decreased significantly over time (p=0.011 and p=0.001, resp.), with the largest decrease seen at week 24. On the contrary, frequencies of naive Th-cells increased over time on treatment (p<0.001). From week 24 to week 48 (off treatment), a trend towards increased absolute numbers and frequencies of effector memory Th-cells was observed. Decrease and repopulation of this T-cell subset correspond to changes in disease activity as assessed with ESSDAI.

Conclusion

CTLA-4Ig treatment with Abatacept decreases the presence of circulating effector memory Th-cells of pSS patients. The observation that decrease and repopulation of effector memory Th-cells correspond to changes in disease activity suggests that these cells are -at least partially- responsible for the effects of Abatacept treatment seen in pSS patients.

Disclosure:

G. Verstappen,
None;

W. H. Abdulahad,
None;

P. M. Meiners,
None;

S. Arends,
None;

S. Beijer-Liefers,
None;

A. Vissink,
None;

F. G. M. Kroese,
None;

H. Bootsma,

BMS,

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