Abstract
BackgroundMorphea 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.MethodsAutoantigen 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.ResultsMyelin 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.ConclusionsA 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.
Highlights
Morphea is an autoimmune, sclerosing skin disorder
Patient recruitment We identified 70 morphea patients with active, inflammatory skin lesions along with 35 matched healthy controls and 30 systemic sclerosis (SSc) disease controls to obtain seroprofiles on autoantigen arrays (Additional file 1: Table S1)
Protein array analysis identified a distinct biosignature in morphea patients dominated by myelin basic protein (MBP) antibodies Protein array analysis identifies autoreactive B cell responses in sera from morphea participants
Summary
Morphea is an autoimmune, sclerosing skin disorder. Despite the recent emphasis on immune dysreg‐ ulation in morphea, the role of autoantibodies in morphea pathogenesis or utility as biomarkers are poorly defined. Several potential autoantibody associations have been described in subsets of morphea patients including anti-histone, anti-topoisomerase IIα, anti-U3-smallnuclear-ribonucleoprotein antibody (U3-snRNP), anti-endothelial cell, anti-matrix metalloproteinase 1, and anti-Th/To ribonucleoprotein, among others [4, 6,7,8,9,10,11,12,13]. These studies suggest the possibility that these autoantibodies may be important for pathogenesis or as biomarkers, their role is poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
