Autoantigen microarrays reveal myelin basic protein autoantibodies in morphea.

Abstract

BACKGROUND:

Morphea is an autoimmune, sclerosing skin disorder. Despite the recent emphasis on immune dysregulation in morphea, the role of autoantibodies in morphea pathogenesis or utility as biomarkers are poorly defined.

METHODS:

Autoantigen microarray was used to profile autoantibodies from the serum of participants from the Morphea in Adults and Children (MAC) cohort. Clinical and demographic features of morphea patients with myelin basic protein (MBP) autoantibodies were compared to those without. MBP immunohistochemistry staining was subsequently performed in morphea skin to assess for perineural inflammation in areas of staining. Immunofluorescence staining on mouse brain tissue was also performed using patient sera and mouse anti-myelin basic protein antibody to confirm the presence of MBP antibodies in patient sera.

RESULTS:

Myelin basic protein autoantibodies were found in greater frequency in morphea (n = 50, 71.4%) compared to systemic sclerosis (n = 2, 6.7%) and healthy controls (n = 7, 20%). Patients with MBP antibodies reported pain at higher frequencies. Morphea skin biopsies, highlighted by immunohistochemistry, demonstrated increased perineural inflammation in areas of MBP expression. Immunofluorescence staining revealed an increased fluorescence signal in myelinated areas of mouse brain tissue (i.e. axons) when incubated with sera from MBP antibody-positive morphea patients compared to sera from MBP antibody-negative morphea patients. Epitope mapping revealed target epitopes for MBP autoantibodies in morphea are distinct from those reported in MS, and included fragments 11-30, 41-60, 51-70, and 91-110.

CONCLUSIONS:

A molecular classification of morphea based on distinct autoantibody biosignatures may be used to differentially classify morphea. We have identified anti-MBP as a potential antibody associated with morphea due to its increased expression in morphea compared to healthy controls and systemic sclerosis patients.

• Authors: Jane L Zhu, Ricardo T Paniagua, Henry W Chen, Stephanie Florez-Pollack, Elaine Kunzler, Noelle Teske, Yevgeniya Byekova Rainwater, Quan-Zhen Li, Gregory A Hosler, Wenhao Li, Denise M O Ramirez, Nancy L Monson, Heidi T Jacobe
• Journal: Journal of translational medicine (J Transl Med) Vol. 20 Issue 1 Pg. 41 (01 24 2022) ISSN: 1479-5876 [Electronic] England
• PMID: 35073943 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Autoantibodies
• Autoantigens
• Myelin Basic Protein

Topics

• Animals
• Autoantibodies
• Autoantigens
• Humans
• Mice
• Multiple Sclerosis
• Myelin Basic Protein (metabolism)
• Scleroderma, Localized (complications)