Serum Biomarkers of Immune Activation and Subsequent Risk of Non-Hodgkin B-Cell Lymphoma among HIV-Infected Women
Background: There is increasing evidence that chronic immune activation predisposes to non-Hodgkin's lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the U.S. who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined. Methods: We conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3-5 years, 1-3 years, and 0-1 year prior to AIDS-NHL diagnosis (n=22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4+ T cell count, and study follow-up time (n=78). Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models. Results: Elevated levels of sCD27 (OR=7.21, 95% CI=2.62-19.88), sCD30 (OR=2.64, 95% CI=1.24-5.64), and CXCL13 (OR=2.56, 95% CI=1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a 2-to 4-fold increased risk of AIDS-NHL in certain subgroups, while elevated IL6 was associated with a 2-fold increased risk in the 0-1 year time-window, only. Conclusion: These findings support the hypothesis that chronic B cell activation contributes to the development of AIDS-NHL in women. Impact: sCD23, sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL.
Available from: Brian Flepisi
- "HHV8 antigens target cell signaling pathways and deregulate apoptosis and immune response through vCyclin, vFLIP, bcl-2 oncogene, viral interferon regulating factor, and vIL-6.33,43–47 The alterations of immune cells (lymphocytes, monocytes, histiocytes, and dendritic cells) have been suggested to play a role in the neoplastic process.48 Immune activation can cooperate with some growth factors and HIV-1 Tat protein in the development and progression of KS.49 "
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ABSTRACT: Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer.
07/2014; 6:11-20. DOI:10.4137/BIC.S15056
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ABSTRACT: Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα may serve as biomarkers for AIDS-NHL.
Cancer Epidemiology Biomarkers & Prevention 11/2013; 23(2). DOI:10.1158/1055-9965.EPI-13-0714 · 4.13 Impact Factor
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ABSTRACT: Despite the introduction of highly active antiretroviral therapy or combination antiretroviral therapy (HAART and cART, respectively) patients infected with HIV might develop certain types of cancer more frequently than uninfected people. Lymphomas represent the most frequent malignancy among patients with HIV. Other cancer types that have increased in these patients include Kaposi sarcoma, cancer of the cervix, anus, lung and liver. In the post-HAART era, however, patients with HIV have experienced a significant improvement in their morbidity, mortality and life expectancy. This Review focuses on the different types of lymphomas that generally occur in patients with HIV. The combination of cART and antineoplastic treatment has resulted in remarkable prolongation of disease-free survival and overall survival among patients with HIV who develop lymphoma. However, the survival in these patients still lags behind that of patients with lymphoma who are not infected with HIV. We also provide an update of epidemiological data, diagnostic issues, and strategies regarding the most-appropriate management of patients with both HIV and lymphomas.
Nature Reviews Clinical Oncology 03/2014; 11(4). DOI:10.1038/nrclinonc.2014.31 · 14.18 Impact Factor
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