MDA5

Product Information

MDA5 (Melanoma differentiation-associated protein 5) is an important marker in Myositis diagnostics, particularly dermatomyositis. It is associated with the subgroup amyopathic dermatomyositis and linked with rapidly progressing interstitial lung disease (RP-ILD). Patients with MDA5 positive dermatomyositis and RP-ILD have a particularly poor prognosis which makes this marker so important. Early detection and management of patients at risk for RP-ILD, are crucial. Including MDA5 in diagnostic panels can aid in the timely diagnosis and treatment of this severe condition.

MDA5 protein is a cytosolic RNA helicase and part of the RIG-I-like receptor family. The helicase plays an important role in the recognition of viral double stranded RNA and the activation of antiviral immune responses. MDA5 contains two N-terminal CARD domains that initiate the signalling cascade of the immune response, the central ATP-dependent helicase domain, and the C-terminal domain which is responsible for recognition and binding of the RNA.

Current research indicates that dominant autoantigenic epitopes of MDA5 are mostly located in the central helicase region. These epitopes are predominantly conformational, suggesting that the native tertiary structure of MDA5 is critical for autoantibody recognition in anti-MDA5-positive dermatomyositis. Other experiments demonstrate that the N-terminus and the C-terminus of MDA5 antigen are most prominently recognised by patient autoantibodies.

AROTEC MDA5 antigen is the full length, human MDA5 protein with a hexa-histidine tag, recombinantly produced in insect cells. The antigen is supplied in its folded, soluble form ensuring presence of all epitopes, the linear epitopes as well as the important conformational epitopes.

MDA5 antigen is part of a comprehensive Myositis panel developed at AROTEC.

Clinical Indications

Dermatomyositis (DM)

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MSDS

References

1. Fuzzi E, Gatto M, Zen M, et al. Anti-MDA5 dermatomyositis: an update from bench to bedside. Curr Opin Rheumatol. Nov 1 2022;34(6):365-373.

2. Wu B, Peisley A, Richards C, et al. Structural Basis for dsRNA Recognition, Filament Formation, and Antiviral Signal Activation by MDA5. Cell. 2013;152(1):276-289.

3. Van Gompel E, Demirdal D, Fernandes-Cerqueira C, et al. Autoantibodies against the melanoma differentiation–associated protein 5 in patients with dermatomyositis target the helicase domains. Rheumatology. 2024;63(5):1466-1473.

4. Mo Y, Ye Y, Peng L, Sun X, Zhong X, Wu R. The central helicase domain holds the major conformational epitopes of melanoma differentiation–associated gene 5 autoantibodies. Rheumatology. 2024;63(5):1456-1465.

5. Yamaguchi K, Poland P, Bijoy George T, et al. Correlation between B-cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis. Rheumatology. 2024;63(7):2016-2023.