ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1652

Autophagy May Contribute To Glucocorticoid Resistance In Patients With Myositis By Maintaining T Lymphocytes Homeostasis In The Muscles

Mei Zong1, John Jörholt2, Julia Winter2, Eva Lindroos3, Helena E. Harris2 and Ingrid E. Lundberg4, 1Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden, 2Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, 3Department of Medicine, Rheumatology Unit, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden., Stockholm, Sweden, 4Rheumatology Unit, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: T-cell Biology in Autoimmune Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Infiltrating T cells is a typical histopathologic feature in muscles of patients with myositis and these cells are also believed to play important roles in the disease development. In contrast to macrophages which can be reduced after glucocorticoid (GC) treatment, T cells often persist after treatment. The explanation for these persisting T cells after treatment even with high doses of GC is still unclear. Autophagy helps cells to survive under variable cellular stresses. In this context the effects of endogenous, cytosolic high mobility group box 1 (HMGB1) protein is of interest as HMGB1 can induce autophagy by binding Beclin1 (an upstream protein initiating autophagy) and thereby contribute to  cell survival. In this study, we investigated whether autophagy initiated by HMGB1-Beclin1 binding can contribute to T cell survival in the muscles of patients with myositis, and whether this homeostasis of T cells can contribute to the GC resistance.

Methods:

Muscle biopsies were obtained from poly- and dermatomyositis patients with no or limited clinical response to GC and from patients with good response to GC. Biopsies were investigated by immunohistochemistry for macrophages (CD163, CD68), T cells (CD3), HMGB1 and Beclin1. Computer image analysis was performed for each marker. Co-localization of HMGB1, Beclin1 and T cells was done by consecutive section staining and was confirmed by double fluorescence staining.

Results:

Both HMGB1 and Beclin1 expression was detected in muscle tissue of patients with myositis; furthermore, the expression co-localized to the infiltrating T cells as demonstrated by consecutive section staining and double fluorescence staining. Moreover, the expression of HMGB1 and Beclin1 correlated strongly (p=0.002, R=0.8). In five patients who were good responders, the number of T cells in the muscles was decreased after treatment, and simultaneously the HMGB1 and Beclin1 expression was decreased. Analyses are ongoing on the non-responders. According to our hypothesis in these patients T cells will not be reduced after treatment and HMGB1 and Beclin1 expression will maintain at high levels too.  

Conclusion:

Markers of autophagy are present in the invading T cells in muscle tissue of myositis patients. Autophagy initiated by HMGB1-Beclin1 binding may contribute to T cell survival in the muscles of patients with myositis. And this homeostasis in T cells could be a factor that contributes to the GC resistance.

Disclosure:

M. Zong,
None;

J. Jörholt,
None;

J. Winter,
None;

E. Lindroos,
None;

H. E. Harris,
None;

I. E. Lundberg,

BMS,

2,

Novartis Pharmaceutical Corporation,

5.

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