Autoantibodies in Morphea: An Update

Abstract

Skin autoimmune conditions belong to a larger group of connective tissue diseases and primarily affect the skin, but might also involve underlying tissues, such as fat tissue, muscle, and bone. Autoimmune antibodies (autoantibodies) play a role in autoimmune skin diseases, such as localized scleroderma also termed morphea, and systemic scleroderma, also called systemic sclerosis (SSc). The detailed studies on the biological role of autoantibodies in autoimmune skin diseases are limited. This results in a few available tools for effective diagnosis and management of autoimmune skin diseases. This review aims to provide an update on the detection and most recent research on autoantibodies in morphea. Several recent studies have indicated the association of autoantibody profiles with disease subtypes, damage extent, and relapse potential, opening up exciting new possibilities for personalized disease management. We discuss the role of existing autoantibody tests in morphea management and the most recent studies on morphea pathogenesis. We also provide an update on novel autoantibody biomarkers for the diagnosis and study of morphea.

Keywords: autoantibody; diagnostics; morphea; personalized management; skin autoimmunity.

Figure 1

Morphea: (A) Generalized morphea and plaque morphea are the most common subtypes of morphea in adult patients, while (B) linear scleroderma of the trunk, limbs, and head are the most common in pediatric morphea. For each photograph, written informed consent was obtained from the participant for the publication of this image.

Figure 2

Pooled ANA positivity in patients with morphea: (A) The ANA positivity (percentages) in the individual studies are represented by squares, through which the horizontal lines represent the 95% CIs. The thick vertical line represents the pooled ANA positivity from these studies; (B) Funnel plot of the proportion vs. the standard error of the proportion for ANA positivity. The circles represent the trials included in the meta-analysis. The line in the center indicates the summary proportion. The other lines represent the 95% CIs. Asymmetry about the pooled proportion line is consistent with the presence of minimal publication bias.

Figure 3

General overview of morphea autoantibodies in relation to clinical features. Anti-ssDNA, Anti-single stranded DNA; IFNx, Interferon; ILx, Interleukin; SSA, Sjogren's-syndrome-related antigen A; SSB, Sjogren's-syndrome-related antigen B; Scl-70, Topoisomerase I; ACA, Anti-centromere antibody; ECM, Extracutaneous manifestations; SSc, Systemic Sclerosis; SLE, Systemic lupus erythematosus; GM-CSF, Granulocyte-macrophage colony-stimulating factor; VEGF, Vascular endothelial growth factor; Ab, Antibody (, , , , , –30, 37, 38).

Figure 4

Biological mechanisms involved in morphea, and suggested roles of cytokines and autoantibodies.

Figure 5

Synthetic DNA, RNA, and LNA antigens in morphea (56). (A) A general approach to the design including computation, library screening, and ELISA; (B) representative molecular dynamics result for dsDNA antigen and autoantibody showing key interactions contributing to the binding; (C) Representative antigens selected for the study of the pediatric morphea cohort, and correlations of ELISA results with modified localized scleroderma skin severity index (mLOSSI), index of disease damage (LOSDI), and time in treatment. C1 and C2 were commercial controls used in the study, calf thymus DNA, and G-quadruplex human DNA.