Format

Send to

Choose Destination
Arthritis Rheum. 2009 Apr;60(4):1145-51. doi: 10.1002/art.24365.

Lack of detection of agonist activity by antibodies to platelet-derived growth factor receptor alpha in a subset of normal and systemic sclerosis patient sera.

Author information

1
ImClone Systems Corp., New York, New York, USA. Nick.Loizos@ImClone.com

Abstract

OBJECTIVE:

To investigate whether agonist anti-platelet-derived growth factor receptor alpha (anti-PDGFRalpha) antibodies are present in the serum of patients with systemic sclerosis (SSc; scleroderma).

METHODS:

Sera were obtained from healthy subjects and scleroderma patients. An electrochemiluminescence binding assay was performed for detection of serum autoantibodies to PDGFRalpha, PDGFRbeta, epidermal growth factor receptor (EGFR), and colony-stimulating factor receptor 1 (CSFR1). Serum immunoglobulin was purified by protein A/G chromatography. To assess Ig agonist activity, PDGFRalpha-expressing cells were incubated with pure Ig and the level of receptor phosphorylation determined in an enzyme-linked immunoassay, as well as by Western blotting. Ig agonist activity was also assessed in a mitogenic assay and by MAP kinase activation in a PDGFRalpha-expressing cell line.

RESULTS:

Sera from 34.3% of the healthy subjects and 32.7% of the SSc patients contained detectable autoantibodies to PDGFRalpha and PDGFRbeta, but not EGFR or CSFR1. Purified Ig from these sera was shown to retain PDGFR binding activity and, at 200-1,000 microg/ml, exhibited no agonist activity in a cell-based PDGFRalpha phosphorylation assay and did not stimulate a mitogenic response or MAP kinase activation in a PDGFRalpha-expressing cell line. Two purified Ig samples that were unable to bind PDGFRalpha did exhibit binding activity to a nonglycosylated form of PDGFRalpha.

CONCLUSION:

Although approximately one-third of sera from scleroderma patients contained detectable autoantibodies to PDGFR, these antibodies were not specific to scleroderma, since they were also detected in a similar percentage of samples from normal subjects. PDGFRalpha agonist activity was not demonstrated when purified Ig from these sera was tested in cell-based assays.

PMID:
19333919
DOI:
10.1002/art.24365
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center