TY - JOUR
T1 - Autoantigen microarrays reveal myelin basic protein autoantibodies in morphea
AU - Zhu, Jane L.
AU - Paniagua, Ricardo T.
AU - Chen, Henry W.
AU - Florez-Pollack, Stephanie
AU - Kunzler, Elaine
AU - Teske, Noelle
AU - Rainwater, Yevgeniya Byekova
AU - Li, Quan Zhen
AU - Hosler, Gregory A.
AU - Li, Wenhao
AU - Ramirez, Denise M.O.
AU - Monson, Nancy L.
AU - Jacobe, Heidi T.
N1 - Funding Information:
We would like to acknowledge William Robinson’s, MD, PhD, Associate Professor of Medicine, Stanford University School of Medicine, Stanford, CA, invaluable contribution to this work. The authors would also like to thank The University of Texas Health Science Center at Houston Scleroderma Registry for donation of controls. The authors would like to acknowledge the assistance of the UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, 1P30 CA142543-01, for access to the Zeiss LSM 880 confocal microscope. All work was performed in Dallas, Dallas County, Texas, USA.
Funding Information:
We would like to acknowledge William Robinson’s, MD, PhD, Associate Professor of Medicine, Stanford University School of Medicine, Stanford, CA, invaluable contribution to this work. The authors would also like to thank The University of Texas Health Science Center at Houston Scleroderma Registry for donation of controls. The authors would like to acknowledge the assistance of the UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, 1P30 CA142543-01, for access to the Zeiss LSM 880 confocal microscope. All work was performed in Dallas, Dallas County, Texas, USA.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Antibody
KW - Morphea
KW - Myelin basic protein
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U2 - 10.1186/s12967-022-03246-5
DO - 10.1186/s12967-022-03246-5
M3 - Article
C2 - 35073943
AN - SCOPUS:85123492289
SN - 1479-5876
VL - 20
JO - Journal of translational medicine
JF - Journal of translational medicine
IS - 1
M1 - 41
ER -