Immune complexes containing scleroderma-specific autoantibodies induce a profibrotic and proinflammatory phenotype in skin fibroblasts

Arthritis Research & Therapy
E RaschiM O Borghi

Abstract

In systemic sclerosis (SSc), autoantibodies provide the most accurate tool to predict the disease subset and pattern of organ involvement. Scleroderma autoantibodies target nucleic acids or DNA/RNA-binding proteins, thus SSc immune complexes (ICs) can embed nucleic acids. Our working hypothesis envisaged that ICs containing scleroderma-specific autoantibodies might elicit proinflammatory and profibrotic effects in skin fibroblasts. Fibroblasts were isolated from skin biopsies obtained from healthy subjects and patients with diffuse cutaneous SSc (dcSSc). ICs were purified by polyethylene-glycol precipitation from sera of SSc patients bearing different autoantibodies. ICs from patients with systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS) and from normal healthy subjects (NHS) were used as controls. After incubation with ICs, fibroblasts were evaluated for ICAM-1 expression, interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-2, tumor growth factor (TGF)-β1 and Pro-CollagenIα1 secretion, collagen (col)Iα1, mmp-1, toll-like receptor (tlr)2, tlr3, tlr4, tlr7, tlr8, tlr9, interferon (ifn)-α, ifn-β and endothelin-1 mRNA, and NFκB, p38MAPK and SAPK-JNK act...Continue Reading

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Feb 13, 2020·Clinical and Experimental Immunology·L Frasca, R Lande
Nov 15, 2018·Immunology and Cell Biology·Alice BallerieValérie Lecureur
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Jul 8, 2021·Annals of the Rheumatic Diseases·Kristina Elizabeth Neergaard ClarkChristopher P Denton

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Methods Mentioned

BETA
biopsies
flow cytometry
ELISA
ELISAs
PCR
Assay
Protein Assay
electrophoresis

Software Mentioned

ImageJ

Related Concepts

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Antiphospholipid Syndrome

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