Research Article HLA-G Dimers in the Prolongation of Kidney Allograft Survival Maureen Ezeakile, 1 Vera Portik-Dobos, 1 Juan Wu, 1 Daniel D. Horuzsko, 1 Rajan Kapoor, 2 Muralidharan Jagadeesan, 2 Laura L. Mulloy, 2 and Anatolij Horuzsko 1 1 Molecular Oncology and Biomarkers Program, Cancer Center, Department of Medicine, Georgia Regents University, 1410 Laney Walker Boulevard, Augusta, GA 30912, USA 2 Section of Nephrology, Hypertension, and Transplantation Medicine, Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA Correspondence should be addressed to Anatolij Horuzsko; ahoruzsko@gru.edu Received 8 December 2013; Revised 23 February 2014; Accepted 27 February 2014; Published 30 March 2014 Academic Editor: Enrico Fainardi Copyright © 2014 Maureen Ezeakile et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Human leukocyte antigen-G (HLA-G) contributes to acceptance of allograts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with signiicantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA- G and its speciic receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograt survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinlammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inlammatory state. 1. Introduction Human leukocyte antigen-G (HLA-G) is a natural molecule involved in the establishment and maintenance of maternal tolerance to semiallogeneic fetal tissues [1–6]. Decreased expression of HLA-G during pregnancy has been noted as a contributing factor to preeclampsia and multiple mis- carriages [7–11]. In addition, HLA-G expression has been identiied in pancreas, adult thymic cells, and stem cells, as well as in pathological conditions including cancer, trans- plantation, HIV infection, and inlammatory diseases [12– 27]. HLA-G binds to several receptors, including ILT2, ILT4, and KIR2DL4 receptors, to inhibit immune responses of myelomonocytic cells, dendritic cells, T cells, B cells, and NK cells [5, 28–35]. In addition to membrane-bound forms (HLA-G1, -G2, -G3, and -G4), HLA-G is also presented by several soluble isoforms (sHLA-G1, -G5, -G6, and -G7) generated through two mechanisms: alternative splicing and proteolytic release, which is known to be mediated by metalloproteases [36, 37]. Signiicantly high levels of sHLA- G were determined in several physiological and pathological conditions, including an association with higher pregnancy and implantation rates [8]. It has been determined that a high level of sHLA-G is correlated with clinical manifestation of several diseases, rheumatoid arthritis, systemic lupus ery- thematosus, asthma, and HIV infection. Increased levels of sHLA-G were correlated with disease progression in patients with hematological malignancies and solid tumors, including patients with acute leukemia, lymphoma, chronic lymphatic leukemia, melanoma, breast cancer, glioma, and renal and lung carcinomas [25, 38]. Recent studies showed that sHLA- G molecules are involved in prolongation of allograt survival in patients with organ/tissue transplantation [39–41]. In most studies plasma/serum levels of HLA-G was determined by ELISA. However, HLA-G-speciic ELISA has limitations and does not discriminate the presence of monomer or dimer isoforms of HLA-G. New data has revealed that disulide- linked dimeric complexes of HLA-G have high preferential Hindawi Publishing Corporation Journal of Immunology Research Volume 2014, Article ID 153981, 10 pages http://dx.doi.org/10.1155/2014/153981