Autoantibodies in systemic sclerosis: unanswered questions.

Cristiane Kayser,Marvin J Fritzler

doi:10.3389/fimmu.2015.00167

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review, we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis.

Highlights

Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease (ARD) of unknown etiology characterized by microvascular abnormalities, cutaneous and visceral fibrosis all accompanied by signature immune abnormalities
SSc patients are classified as diffuse cutaneous SSc, characterized by widespread and rapidly progressive skin thickening, and earlier and more severe internal organ involvement, or limited cutaneous SSc in which skin thickening is restricted to the distal extremities and face, and accompanied by less severe and later onset internal organ involvement (1)
Some of them are considered highly specific for SSc, including anti-topoisomerase 1 (ATA), anti-centromere (CENP), and anti-RNA polymerase III, and these were recently added to the 2013 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) SSc classification criteria (4)

Summary

INTRODUCTION

Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease (ARD) of unknown etiology characterized by microvascular abnormalities, cutaneous and visceral fibrosis all accompanied by signature immune abnormalities. SSc is a heterogeneous disease with a broad range of manifestations, including Raynaud’s phenomenon, and cutaneous, gastrointestinal, renal, cardiovascular, and pulmonary involvement. Autoantibodies that are reported in other ARD can be present in SSc, including antiPM/Scl, anti-Ku, anti-U1-RNP, anti-SS-A/Ro60, and anti-NOR 90 (Table 1). AUTOANTIBODIES IN SSc Anti-topoisomerase I antibodies (ATA) were initially named anti-Scl-70 because they reacted with a 70 kDa protein on immunoblots. ATA have been reported in 15–42% of SSc patients, with a specificity ranging from 90 to 100% (2, 8). SSc patients with ATA have a higher risk of having severe pulmonary fibrosis and cardiac involvement. The presence of ATA in patients with Raynaud’s phenomenon is predictive in that they are associated with a high risk of developing of SSc (9)

Mild internal organ involvement

Findings

Stimulation of the production of ROS and collagen by fibroblasts