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Potential role of type I interferon/IP-10 axis in the pathogenesis of anti-MDA5 antibody-positive dermatomyositis
A. Kokuzawa1, J. Nakamura2, Y. Kamata3, K. Sato4
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan. satok@jichi.ac.jp
CER16192
2023 Vol.41, N°2
PI 0275, PF 0284
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PMID: 36622131 [PubMed]
Received: 06/09/2022
Accepted : 16/12/2022
In Press: 09/01/2023
Published: 01/03/2023
Abstract
OBJECTIVES:
Dermatomyositis (DM) patients with anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are known for poor prognosis. This study was designed to identify humoral factors that are readily detectable in the disease and may reflect its activity and pathophysiology.
METHODS:
We first quantified the serum level expression of 28 cytokines in the serum of patients with collagen vascular diseases using bead-based multiplex immunoassays. We completed these evaluations at hospital admission and followed up with three DM patients with anti-MDA5 antibodies during hospitalisation. We also performed an immunohistochemical analysis of skin samples obtained from two patients.
RESULTS:
The serum level of interferon gamma-induced protein 10 (IP-10) was significantly higher in DM patients with anti-MDA5 antibodies than in those without the antibody, decreasing drastically upon treatment. Interestingly, this time course paralleled not that of interferon (IFN)-γ, which was originally reported to be the inducer of IP-10, but that of IFN-α2. Immunohistochemical analysis revealed that most of the IP-10-positive cells were macrophages. Furthermore, monocytes stimulated with type I IFN in vitro produced IP-10 in a dose-dependent manner.
CONCLUSIONS:
IP-10 is a potentially useful disease activity marker of DM with anti-MDA5 antibodies, correlating more with IFN-α2 then IFN-γ. IP-10 released from macrophages might prompt the infiltration of macrophages themselves. Thus, the type I IFN/IP-10 axis may play a pivotal role in the pathogenesis of this intractable disease.
