Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

Gabriele Valentini,Michele Iudici,Aldo Ciani,Alberto Spanò,Serena Vettori,Carlo Santoriello,Francesco Bondanini,Domenico Cozzolino,Salvatore Cappabianca,Filiberto Vitelli,Giovanna Cuomo,Antonella Marcoccia,Giovanni Maria De Matteis

doi:10.1186/ar4236

Abstract

IntroductionEarly systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.MethodsSeventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.ResultsThirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.ConclusionThese results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.

Highlights

Systemic sclerosis (SSc) is characterized by Raynaud’s phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of systemic sclerosis (SSc)
Koenig and colleagues validated the LeRoy and Medsger criteria in a large 20-year prospective study [2]. They found that, at the last follow-up, patients presenting with SSc marker autoantibodies and a scleroderma pattern at capillaroscopy, with no other manifestation distinctive of the disease other than puffy fingers and/or arthritis, had developed definite SSc 60 times more frequently than patients presenting with only Raynaud’s phenomenon (RP)
We evaluated whether clinical, preclinical functional or cellular activation markers are related to distinct early SSc subsets at presentation by merging our early SSc cohort with that recruited at a secondary Angiology Unit, where a significant number of patients with early SSc were SSc marker antibodynegative and capillaroscopy-positive

Summary

Introduction

Systemic sclerosis (SSc) is characterized by Raynaud’s phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Koenig and colleagues validated the LeRoy and Medsger criteria in a large 20-year prospective study [2]. They found that, at the last follow-up, patients presenting with SSc marker autoantibodies and a scleroderma pattern at capillaroscopy (referred to as subset 1 in the present paper), with no other manifestation distinctive of the disease other than puffy fingers and/or arthritis, had developed definite SSc 60 times more frequently than patients presenting with only RP. Koenig and colleagues suggested that such cases be labeled collectively as early SSc

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