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Functional autoantibodies in systemic sclerosis

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Abstract

Functional autoantibodies are an emerging field of research that focuses on the effects of these immunoglobulins when they bind to their target molecules. Accumulating information now exists about the molecular targets and precise binding mechanisms of functional autoantibodies as well as about their downstream effects. These data raise the need to distinguish functional autoantibodies from non-functional autoantibodies with regard to their ability to stimulate or to inhibit their target protein via binding. The presence of autoantibodies has been documented in autoimmune disorders decades ago, but meanwhile, more and more autoantibodies have been identified as functional, acting as pathogenic drivers involved in the induction of organ-specific damage in systemic sclerosis as well as in other autoimmune disorders. These findings offer new opportunities for the development of novel therapeutic strategies.

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Abbreviations

aAbs:

Autoantibodies

ACA:

Anti-centromere aAbs

AECA:

Anti-endothelial cell aAbs

AFA:

Anti-fibroblast aAbs

Alpha-SMA:

Alpha-smooth muscle actin

ANA:

Anti-nuclear aAbs

Anti-RNAP:

Anti-RNA polymerase I/III aAbs

ATA:

Anti-topoisomerase I aAbs

beta-AR:

Beta-adrenergic receptor

CCL18:

Chemokine (C–C motif) ligand 18

CHO:

Chinese hamster ovary

CMV:

Cytomegalovirus

dcSSc:

Diffuse cutaneous SSc

ECM:

Extracellular matrix

ELISA:

Enzyme-linked immunosorbent assay

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinases

EUSTAR:

European Scleroderma Trials and Research group

GPCR:

G protein-coupled receptor

HSCT:

Hematopoietic stem cell transplantation

IA:

Immunoadsorption

IAS:

Internal anal sphincter

ICAM-1:

Intercellular adhesion molecule 1

IgG:

Immunoglobulin G

IL-:

Interleukin

ILD:

Interstitial lung disease

lcSSc:

Limited cutaneous SSc

LF:

Lung fibrosis

M2R:

Muscarinic type 2 receptor

M3R:

Muscarinic type 3 receptor

MMP:

Matrix metalloproteinase

mRSS:

Modified Rodnan skin score

NAG-2:

Novel antigen 2

NK:

Natural killer

PAH:

Pulmonary arterial hypertension

PBMCs:

Peripheral blood mononuclear cells

PDGR:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

PKC:

Protein kinase C

RNP:

Ribonucleoprotein

ROS:

Reactive oxygen species

SLE:

Systemic lupus erythematosus

SMCs:

Smooth muscle cells

SS:

Sjögren’s syndrome

SSc:

Systemic sclerosis

SSc-IgG:

Purified IgG from SSc patients

TSaAbs:

TSHR-stimulating aAbs

TBaAbs:

TSHR blocking aAbs

TSH:

Thyroid-stimulating hormone

TSHR:

Thyroid-stimulating hormone receptor

TGFbeta:

Transforming growth factor-beta

VCAM-1:

Vascular cell adhesion molecule 1

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Acknowledgments

We thank Harald Heidecke and the employees of Celltrend GmbH for the analysis of anti-AT1R and anti-ETAR aAb serum levels.

Conflict of interest

The authors declare that they have no competing interests.

Funding

The studies were supported by the intramural grant of the University Hospital Charité, by the German Systemic Sclerosis Network (DNSS), by the Scleroderma Foundation, and by the Mirjam Lichy Foundation. The funders had no involvement in the study designs, in the collection, analysis and interpretation of the data, in the writing of the manuscript, and in the decision to submit the paper for publication.

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Correspondence to Gabriela Riemekasten.

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This article is a contribution to the special issue on Immunopathology of Systemic Sclerosis - Guest Editors: Jacob M. van Laar and John Varga

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Günther, J., Rademacher, J., van Laar, J.M. et al. Functional autoantibodies in systemic sclerosis. Semin Immunopathol 37, 529–542 (2015). https://doi.org/10.1007/s00281-015-0513-5

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