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J Rheumatol. 2010 Nov;37(11):2286-9. doi: 10.3899/jrheum.100454. Epub 2010 Sep 1.

Increased production of a proliferation-inducing ligand (APRIL) by peripheral blood mononuclear cells is associated with antitopoisomerase I antibody and more severe disease in systemic sclerosis.

Author information

1
Department of Orthopedics and Traumatology, Medical University of Bialystok, Bialystok, Poland.

Abstract

OBJECTIVE:

A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor (TNF) family, plays a crucial role in the survival of peripheral B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of autoimmune phenomena. We evaluated the capacity of peripheral blood mononuclear cells from patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations between production of APRIL by SSc-PBMC and clinical and laboratory features of the disease.

METHODS:

PBMC from 20 patients with SSc and 14 healthy subjects were incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were determined in cell culture supernatants by ELISA.

RESULTS:

PBMC from patients with SSc produced significantly more APRIL (961 ± 151 pg/ml/10⁵ cells) than control PBMC (798 ± 219 pg/ml/10⁵ cells; p < 0.01). In patients with SSc, increased production of APRIL was associated with the presence of diffuse skin involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I) antibodies. Multivariate regression analysis revealed anti-topo I antibodies as the only independent predictor of high production of APRIL by PBMC.

CONCLUSION:

Production of APRIL is increased in SSc-PBMC and is associated with the presence of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway might represent a therapeutic possibility for treatment of patients with SSc, in particular those with anti-topo I antibodies.

PMID:
20810514
DOI:
10.3899/jrheum.100454
[Indexed for MEDLINE]

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