Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis.

Marcin Okrój,Anna M Blom,Roger Hesselstrand,Tore Saxne,Martin Johansson

doi:10.1186/s13075-016-1168-x

Marcin Okrój, Anna M Blom + Show 3 more

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https://doi.org/10.1186/s13075-016-1168-x

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Abstract

BackgroundThe complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc.MethodsThe presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation.ResultsBiomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC.ConclusionsThe data indicate that complement activation is an important feature of SRC.

Highlights

The complement system has been implicated in pathogenesis of systemic sclerosis (SSc)
The complement system is activated in patients with autoimmune diseases We tested three different complement activation markers: (1) C4d, corresponding to activation of the classical pathway; (2) the fluid-phase alternative C3 convertase (C3bBbP), reflecting activation of the alternative pathway as well as the amplification loop enhancing the cascade at the level of convertases; and (3) soluble Terminal complement complex (TCC) (sTCC), which evaluates the lytic pathway (Fig. 1)
When overall distribution of autoantibodies was analysed by the Kruskal-Wallis test, we found a significant difference for sTCC (p = 0.016) and a difference on the border of significance for C3bBbP (p = 0.055)

Summary

Introduction

The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. Scleroderma, termed systemic sclerosis (SSc), is an autoimmune disease of connective tissue. Its pathology involves excessive collagen production, resulting in fibrosis of skin and internal organs [1, 2] This condition is accompanied by microangiopathy of varying severity and locations, most obviously seen as Raynaud’s phenomenon. The most widely accepted classification distinguishes two main subtypes: limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) [3]. In the latter case, internal organs, most typically the kidneys, gastrointestinal tract, heart and lungs, are more severely affected.

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