Baroni SS et al. (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 354: 2667–2676

A rigorous, international study published in the New England Journal of Medicine has demonstrated the presence of IgG autoantibodies that stimulate the fibroblast receptor for platelet-derived growth factor (PDGFR-stimulatory antibodies) in sera from patients with systemic sclerosis (scleroderma).

The authors performed a series of experiments that confirmed that these antibodies recognized and activated native PDGFR on fibroblasts. In vitro, purified PDGFR-stimulatory antibodies triggered pathways that resulted in the intracellular generation of reactive oxygen species and upregulation of type I collagen gene expression, as well as conversion of human primary fibroblasts to an active, myofibroblast phenotype. Baroni et al. suggest that these effects could account for the oxidative stress and fibrosis that are the cellular and systemic hallmarks, respectively, of systemic sclerosis.

Sera from 46 white patients (38 women) with systemic sclerosis, who had not taken immunosuppressive medication in the previous 6 weeks, were compared with sera from 20 control individuals (matched for age, sex and ethnicity), as well as with sera from 54 individuals with a range of autoimmune conditions. All of the patients with systemic sclerosis, and none of the other individuals, were positive for PDGFR-stimulatory antibodies.

The authors noted that PDGFR-stimulatory antibodies did not completely replicate the effects of PDGF: they hypothesize that these autoantibodies generate a more persistent stimulus than PDGF does. Direct proof of the causative role of these antibodies in systemic sclerosis, however, awaits in vivo studies in large, ethnically diverse populations of patients.