The antibody levels for each individual are plotted around the values for the different groups were calculated using the Mann Whitney test. Patients Rabbit Polyclonal to C-RAF (phospho-Thr269) with HPV-driven cervical malignancy and oropharyngeal malignancy often show serum antibodies against the E6 and E7 viral proteins [9, 10]. at least four cancer-associated viruses. Antibody profiles against these and other infectious brokers could be useful for enhancing the clinical management of HIV patients. 1. Introduction It is estimated that approximately 18% of all human cancers are caused by infectious brokers [1]. A bulk of these cancers are caused by the seven known cancer-associated viruses including Epstein-Barr computer virus (EBV), hepatitis B computer virus (HBV), human T-lymphotropic virus-I (HTLV-I), human papilloma computer virus (HPV), hepatitis C computer virus (HCV), Kaposi’s sarcoma herpesvirus (KSHV; also known as HHV-8), and Merkel cell polyomavirus (MCV) [2]. Although HIV is not a cancer-causing computer virus, HIV-infected individuals are particularly vulnerable for developing several infection-related malignancies compared to the general populace [3C6]. Mechanistically, the increase in malignancy seen in AIDS patients is due to HIV-associated immune suppression and the higher rates of contamination by several cancer-associated viruses. In particular, HIV-infected individuals show a high incidence of three AIDS-defining malignancies including KSHV-associated Kaposi sarcoma (KS), HPV-driven invasive cervical malignancy, and EBV-associated and nonassociated non-Hodgkin lymphoma (NHL). For KS and NHL, there is a 310-fold and 113-fold higher likelihood, respectively, of developing these malignancies in HIV-infected individuals compared to the general populace [4]. There are also other malignancies that are considered AIDS associated including anal malignancy, lung malignancy, testicular germ cell tumors, and Hodgkin disease, which are more common in HIV than in the general populace, but the causative brokers are less well defined [6, 7]. New tools are needed for identifying individuals who are at risk of developing cancer-virus-associated malignancies, particularly in HIV-infected populations. In general, antibody-based detection of a virus has an advantage over other methods because it can detect both current and previous infections JDTic dihydrochloride [8]. Antibody-based detection is also especially critical for the diagnosis of many viruses where nucleic acid amplification is not sensitive enough to detect the low levels of viral nucleic acids in plasma after initial contamination. For five of the cancer-associated viruses, EBV, HBV, HCV, HTLV-1, and KSHV, the detection of the corresponding antibodies against these brokers is only useful for diagnosis of contamination and cannot necessarily be used as a biomarker of malignancy. However, the detection of antibodies against certain viral proteins can be specific markers for the presence of the corresponding cancers. JDTic dihydrochloride For example, anti-E6 and anti-E7 HPV antibodies and anti-T antigen MCV antibodies are often only observed in patients with HPV-driven cancers [9, 10] and Merkel cell carcinoma [11], respectively. Despite these and other findings, the spectrum of coinfection by the seven cancer-causing viruses and the corresponding antibody levels has not been analyzed in HIV-infected or other human populations. We have developed the luciferase immunoprecipitation system (LIPS) as a facile platform to quantitatively measure antibodies against a diverse spectrum of infectious brokers [8]. LIPS detects strong antibody responses over a wide dynamic range and has been useful for the diagnosis of over 15 different infectious brokers including numerous fungal, bacterial, filarial, and viral pathogens. In addition to using LIPS for highly useful infectious disease diagnostics, LIPS-based antibody profiles can distinguish unique conditions caused by single infectious brokers including HTLV [12, 13], KSHV [14], EBV [15], and HIV [16]. For example, LIPS profiling of the EBV antigens showed much higher antibody levels in chronic active EBV patients compared to healthy blood donors [15]. Similarly, antibody profiling of lytic and latent KSHV antigens distinguished patients with multicentric Castleman’s disease from Kaposi sarcoma [14]. Because of these advantages for studying single infectious brokers, LIPS is usually a promising technology for developing comprehensive antibody profiles against multiple infectious brokers. Here, LIPS JDTic dihydrochloride was used to explore, in parallel, the infection status and antibody levels against all seven cancer-associated viruses in HIV-uninfected individuals and HIV-infected patients with OLP, KS, and NHL. 2. Material and Methods 2.1. Study Patient Samples Informed written consent was obtained from all subjects in accordance with the human experimentation guidelines of the Department of Health and Human Services under multiple IRB-approved protocols, and the studies were conducted according to the principles expressed in the Declaration of.
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