Jie Qian

BACKGROUND: The reasons for long-term marginal bone loss around oral implants are not well understood. PURPOSE: The aim of this paper is to analyze presented evidence behind anticipated reasons for long-term marginal bone loss around oral implants. MATERIALS AND METHODS: A computerized research was conducted on PubMed in April 2011 with the following keywords: oral implants and marginal bone resorption/crestal bone loss/bone loss/bone resorption. This search resulted in a total of one thousand one hundred ninety-four papers of which seven hundred fifty-three were clinical contributions. Further search and filtering finally resulted in 21 experimental studies and one hundred sixteen clinical studies, which were reviewed. RESULTS: No evidence was found that primary infection caused marginal bone resorption. Clinical papers that have reported high levels of peri-implantitis were not supported by data given. Clinical evidence was presented that the so-called combined factors (implant hardware, clinical handling, and patient characteristics) may lead to marginal bone resorption. However, once tissue damage has been caused by combined factors, inflammation and/or infection may develop secondarily and then result in peri-implantitis that may need particular clinical treatment. CONCLUSIONS: As marginal bone loss primarily depends on numerous background factors, it seems logical that, for example, the use of poorly constructed implants placed and handled by untrained clinicians may result in high numbers of patients with secondary problems in form of peri-implantitis; having said this, control of combined factors may likewise lead to very good clinical results where peri-implantitis would represent a very rare disease indeed even at follow-up times of 10 years or more.

Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen-matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.

Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)–driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b ( Mef2b )’s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax . ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity.