br Subjects and Methods br Results br Discussion HnRNP A

Subjects and Methods
Results
Discussion HnRNP A1 has been reported as an important autoantigen of the autoimmune response in rheumatic diseases in many articles. Autoantibodies to hnRNP complex have been detected in patients with RA, SLE and mixed connective tissue disease in succession (so RA and SLE are chosen in this study as disease control) (Hassfeld et al., 1989; Isenberg et al., 1994). Recent researches indicated that hnRNP A1 can become target for autoantibodies in other autoimmune diseases, such as systemic sclerosis, Sjogren\'s syndrome, dermatomyositis (Generini et al., 2009; Op De Beéck et al., 2012) which supposed that hnRNP A1 may contribute in the regulation of inflammation (Noguchi et al., 2009). Compared with other classic disease specific autoantibodies (such as anti-SSA and CCP), autoantibodies to the hnRNP-A1 display a more common feature and exist in many rheumatic diseases (Steiner et al., 1996). Thus we believed that hnRNP A1 was not a candidate diagnostic marker in clinical application for all BD patients. In this study, hnRNP A1 was firstly identified also as a target antigen of BD. About 30% BD patients have circulating order PCI-34051 to hnRNP A1 in Han Chinese (both the independent ELISA and WB assay got the similar results). By comparing the clinical information between the anti-hnRNP A1 antibody positive and negative groups, DVT showed a significant higher in the anti-hnRNP A1 antibodies positive group (P<0.05). Many proteins have been proved with close relationship with BD process. Serum endocan levels as a marker of disease activity in patients with BD has been found (Balta et al., 2014a, 2014b, 2014c). However, the relationship between hnRNP A1 and DVT has not been reported. Intriguingly, existing literatures have proved that hnRNP A1 was related to virus infection (Lin et al., 2009; Kim et al., 2007). Many researchers believed that the onset of BD is associated with microbial infection. Sometimes anti-HSV antibody can be detected in the circulation serum of BD patients (Sohn et al., 2001), furthermore, the role of Streptococcussanguis in BD immunopathogenesis has been reported in several studies before (Mizushima, 1989; Isogai et al., 1990). HnRNP A1 may be a considerable molecular in the process of BD pathology by mediating infection of pathogenic microorganisms, further inducing the endothelial cells dysfunction, initiating inflammatory response and triggering a stronger autoimmune response. Future work will focus on developing high specificity in vitro anti-hnRNP A1 immunoassay as well as striving to extend the assay to more autoimmune disease patients from multi-medical centers. And the co-exist condition of hnRNP A1, hnRNP A2/B1 and relevant peptides will be measured.
Author\'s contributions
Conflicts of interest
Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 81571592, 31371203), Beijing Nova Program of Science and Technology (No. 2007B024), and Program for New Century Excellent Talents in University (No. NECT-12-0773).
Introduction Natural Killer (NK) cells are cytolytic innate lymphoid cells (ILCs) that secrete an array of cytokines and chemokines (Spits et al., 2013; Vivier et al., 2011). Our knowledge of the biology of these cells has greatly increased over the last two decades, but the exact functions of human NK cells in vivo remain elusive. Indeed, the principal known functions of NK cells, such as the control of viral infections and cancers, were identified in studies on mice, and few data are available for humans (Vivier et al., 2011). One major obstacle to be overcome in studies of the role of NK cells in humans is the rarity of selective and well defined NK cell deficiencies (Jouanguy et al., 2013). Isolated NK cell deficiencies are exceptional, and full clinical phenotypes are not always available for the rare affected patients (Gineau et al., 2012; Hughes et al., 2012; Casey et al., 2012). It has been suggested that isolated NK cell lymphopenia is not associated with a particular clinical phenotype. This is the case in children with severe combined immunodeficiencies (SCID) with an NK− phenotype before hematopoietic stem cell transplantation (HSCT). The NK cell compartment is not successfully reconstituted after HSCT in a significant proportion of these patients (low NK cell count<50×106/L), and the incidence of clinical events in these patients is similar to that in patients with normal NK cell counts (Neven et al., 2009). This may reflect redundancy between NK cell responses and other types of immune response, as such redundancy is frequently observed in immunity (Nish and Medzhitov, 2011). We therefore reasoned that the impact of an NK cell deficiency might be revealed by studies of patients presenting other immune defects. We explored the clinical phenotypes of patients with severe NK cell lymphopenia and compared them with those of patients with mild or normal NK cell counts, in a large cohort of patients with common variable immunodeficiency (CVID) from the French DEFI study.