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.
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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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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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DOI: https://doi.org/10.1007/s00281-015-0513-5