Immunological evidence and regulatory potential for cell‐penetrating antibodies in intravenous immunoglobulin

• Published in: Clinical & translational immunology Vol. 4; no. 10; pp. e42 - n/a
• Main Authors: Sali, Aggeliki D, Karakasiliotis, Ioannis, Evangelidou, Maria, Avrameas, Stratis, Lymberi, Peggy
• Format: Journal Article
• Language: English
• Published: Australia Nature Publishing Group 01.10.2015; John Wiley & Sons, Inc
• Subjects: Antigens; Autoantibodies; Cell activation; Cell lines; Cytoplasm; Deoxyribonucleic acid; DNA; Effluents; Experiments; Heparan sulfate; Immunoglobulin G; Immunoglobulins; Intravenous administration; Labeling; Localization; Lupus; Microscopy; Original
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1038/cti.2015.18

Anti‐DNA cell‐penetrating autoantibodies have been extensively studied in autoimmune but not in normal sera. We investigated herein the presence and properties of cell‐penetrating antibodies (CPAbs) in intravenous immunoglobulin (IVIg), a blood product of pooled normal human IgG. IVIg cell penetration was observed into various cell lines, as well as cells from several organs of mice injected intravenously with IVIg therapeutic dose. In all cell types examined in vitro and in vivo, intracellular IgG localized in the cytoplasm, in contrast to the nuclear accumulation of disease‐related CPAbs. IVIg was found to rapidly enter cells via an energy‐independent mode. The CPAb‐fraction was isolated and found to be polyreactive to nuclear and cytoplasmic components; although it corresponded to ~2% of IVIg, it accounted for its inhibitory effect on splenocyte activation. Investigation of IVIg cell penetration capacity provides insight into its mechanisms of action and may account for some of its beneficial effects in numerous diseases. Immunology: Antibodies on the inside Research has shown that antibodies from healthy people can get inside cells, a finding that could explain the benefits of antibody therapy. So‐called cell‐penetrating antibodies had previously only been found in patients with autoimmune diseases, such as systemic lupus erythematosus and mixed connective tissue disease, and localized in the nucleus. A new study led by Peggy Lymberi from the Hellenic Pasteur Institute, Greece, shows that such antibodies also exist in healthy people, localizing, however, in the cytoplasm. The researchers exposed cultured human cells and live mice to intravenous immunoglobulin (IVIg), which contains pooled antibodies from thousands of healthy individuals and is used to treat autoimmune and inflammatory diseases. IVIg antibodies accumulated in a variety of cell types and in multiple organs. Antibody accumulation inside immune cells reduced these cells' immune activity, indicating that the cell‐penetrating ability of these antibodies contributes to the effectiveness of therapy with IVIg.