Fcγ receptors mediate internalization of anti‐Ro and anti‐La autoantibodies from Sjögren’s syndrome and apoptosis in human salivary gland cell line A‐253

Abstract

We conclude that anti-Ro and anti-La autoantibodies have pathogenic effects that could depend on binding to Fcgamma receptors.

Sjögren's syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-κB

“…We demonstrated that Abs can access SGEC via Fcg receptors, transmembrane receptors that recognize the Fc part of the IgG, leading to various functional cellular alterations. 20,27 SGEC express the TNF-a receptors and produce the TNF-a cytokine following anti-Ro/SSA Abs internalization 28 responsible for the constitutive activation of NF-kB observed in SGECs derived from patients with SS. The active NF-kB was associated with the downregulation of TNFAIP3, that is, a negative feedback regulator of TNF-a signaling through NF-kB.…”

“…Informed consent for studies involving human subjects was obtained and the studies were conducted according to the tenets of the Declaration of Helsinki Principles. Anti-Ro/SSA Abs were purified from Sjögren IgG fractions 19,20 using Sepharose 4B-Ro affinity columns. The affinity columns were prepared by coupling 5 mg of Ro60 antigen (ImmunoVision, Springdale, AR, USA) per 1 ml of CNBr-activated Sepharose 4B (Amersham Pharmacia Biotech, Sweden).…”

Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies

“…We demonstrated that autoantibodies 27,30,34 SGEC express the receptors for TNF-a and produce the cytokine TNF-a after anti-Ro/SSA Abs internalization. 29,31,39 The actual study results provide more information about the proinflammatory cytokines production by SGEC after autoantibodies treatment, demonstrating that cells release IL-6 and IL-8 in response to anti-Ro/SSA Abs.…”

“…As these autoantibodies have the same effects on SGEC, [27][28][29][30][31][32] we choose to use in this study anti-Ro/SSA Abs because they were isolated more easily from SS sera. Anti-Ro/SSA Abs were purified from a pool of Sjögren IgG fractions obtained from 20 ml of sera of 25 SS patients (n ¼ 25; mean age 48.3 years).…”

Selective TNF-ALPHA Gene Silencing Attenuates Apoptosis in Human Salivary Gland Epithelial Cells

“…Primary Sjogren's syndrome is an autoimmune rheumatic disease that targets salivary and lachrymal glands, leading to glandular atrophy characterized by keratoconjunctivitis sicca and xerostomia; it has no association with other autoimmune diseases (3). Anti-Ro/SSAAbs purified from pSS IgG fraction are able, once they have penetrated viable human salivary gland epithelial cells, to trigger cell death through apoptotic mechanisms, in a caspase-dependent manner, in which both the extrinsic and the intrinsic pathways playa role (1)(2). Our previous report demonstrated that a salivary gland cell line (A-253, ATCC collection) shows TNF-alpha receptors on the cell surface (4), and that anti-Ro/SSAAbs determine a significant release of TNF-alpha, in comparison with cells treated with healthy IgG and untreated control cells, in which no TNF-alpha production was detectable (4).…”