IVIg-mediated amelioration of ITP in mice is dependent on sialic acid and SIGNR1
EUROPEAN JOURNAL OF IMMUNOLOGY
Authors: Schwab, Inessa; Biburger, Markus; Kroenke, Gerhard; Schett, Georg; Nimmerjahn, Falk
Abstract
Intravenous immunoglobulin G (IVIg) therapy is widely used to treat autoimmune and inflammatory diseases. Recent evidence suggests that in mice, splenic resident cells might be important for the anti-inflammatory activity of IVIg in a model of serum transfer arthritis. Splenectomized human immunothrombocytopenia (ITP) patients, however, still respond to IVIg therapy. To investigate whether the requirement of the spleen is essential for mouse ITP, we used a passive model of induced ITP and demonstrated that IVIg activity was functional in splenectomized animals. Further analysis showed that the IVIg-mediated amelioration of platelet phagocytosis was fully dependent on terminal sialic acid residues in the IVIg preparation and could be blocked with a specific ICAM3 grabbing nonintegrin-related 1 (SIGNR1) specific antibody. These results suggest that, similar to the human system, a spleen-independent but sialic acid- and SIGNR1-dependent pathway is responsible for IVIg-mediated suppression of autoantibody-dependent platelet depletion in mice.
Autoantibody biomarkers for the detection of serous ovarian cancer
GYNECOLOGIC ONCOLOGY
Authors: Katchman, Benjamin A.; Chowell, Diego; Wallstrom, Garrick; Vitonis, Allison F.; LaBaer, Joshua; Cramer, Daniel W.; Anderson, Karen S.
Abstract
Objective The purpose of this study was to identify a panel of novel serum tumor antigen-associated autoantibody (TAAb) biomarkers for the diagnosis of high-grade serous ovarian cancer. Methods. To detect TAAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n = 30 cases/30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens and evaluated these with an independent set of serous ovarian cancer sera (n = 30 cases/30 benign disease controls/30 healthy controls). Thirty-nine potential tumor autoantigens were identified and evaluated using an orthogonal programmable ELISA platform against a total of 153 sera samples (n = 63 cases/30 benign disease controls/60 healthy controls). Sensitivities at 95% specificity were calculated and a classifier for the detection of high-grade serous ovarian cancer was constructed. Results. We identified 11-TAAbs (ICAM3, CTAG2, p53, STYXLI, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) that distinguished high-grade serous ovarian cancer cases from healthy controls with a combined 45% sensitivity at 98% specificity. Conclusion. These are potential circulating biomarkers for the detection of serous ovarian cancer, and warrant confirmation in larger clinical cohorts. (C) 2017 Elsevier Inc. All rights reserved.