Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients

Ouedraogo, David Eric; Makinson, Alain; Nils, Kuster; Nagot, Nicolas; Rubbo, Pierre-Alain; Bolloré, Karine; Foulongne, Vincent; Cartron, Guillaume; Olive, Daniel; Reynes, Jacques; Vendrell, Jean-Pierre; Tuaillon, Édouard

doi:10.1007/s10875-012-9766-0

Cited by 12 publications

(6 citation statements)

References 60 publications

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“…In contrast to recent studies by others who concluded that AIDS-NHL risk was associated with either a TH1 (15) or TH2 cytokine pattern (14) preceding NHL diagnosis, there was no strong association seen between most of the TH1 or TH2 cytokines tested and AIDS-NHL risk.…”

Section: Discussioncontrasting

confidence: 99%

“…While initially considered to be a TH2 cytokine, IL-10 is produced by regulatory T cells (Treg) (40), and by monocyte/macrophages, and is a potent B cell-stimulatory factor (41). IP-10, which was strongly associated with risk for AIDS-NHL in this study, as well as in prior work by others (15), is produced by activated macrophages (39). Additionally we found that neopterin, which is an established biomarker for macrophage activation (27,28), is strongly associated with risk for AIDS-NHL.…”

Section: Discussionsupporting

confidence: 89%

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Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Vendrame

Hussain

Breen

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 89%

Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Vendrame

Hussain

Breen

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Of particular interest for A-NHL is IP-10, a leukocyte chemoattractant implicated in the development and progression of B-cell lymphoma. In two recent studies, elevated levels of IP-10 in the sera of HIV-positive individuals were associated with the development of B-cell lymphoma within 0–5 years 22 , [44]. Elevated pretreatment serum levels of IP-10 were also associated with increased likelihood of disease relapse and diminished survival in HIV-uninfected patients with diffuse large B-cell lymphoma [45].…”

Section: Discussionmentioning

confidence: 95%

Circulating Mediators of Inflammation and Immune Activation in AIDS-Related Non-Hodgkin Lymphoma

et al. 2014

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BackgroundNon-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation.MethodsThis was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays.ResultsA subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers.ConclusionsThese findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease.

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“…31,49,59 Other researchers have also reported increased cytokines 60,61 or B cell activation markers (FLC) 62 pre-AIDS-NHL diagnosis. Most recently, Vendrame et al looked at TH1, TH2, and TH17/T follicular helper cells (TFH) cytokines, using multiplexed (Luminex platform) assays, during the one to five years preceding AIDS-NHL diagnosis in 180 AIDS-NHL cases in the MACS.…”

Section: Role Of Immune Activation In Aids-nhl: Epidemiological mentioning

confidence: 98%

Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma

Epeldegui

Martı́nez-Maza

2015

Forum Immun Dis Ther

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HIV infection is associated with a greatly elevated risk for the development of non-Hodgkin lymphoma (NHL), which while diminished, remains elevated in the highly active antiretroviral therapy (HAART) era. Chronic B cell activation, driven by contact with HIV virions, B cell-stimulatory cytokines, viruses (EBV, HPV, HCV), and by high levels of antigenic stimulation occurs in HIV infected persons, and it is seen at even higher levels in those who go on to develop AIDS-NHL. Evidence from multiple studies indicates that elevated serum levels of several B cell-stimulatory cytokines and biomarkers are seen preceding AIDS-NHL, as well as in immunocompetent persons that develop NHL. Phenotypic changes in circulating B cells also are seen preceding AIDS-NHL, including the expression of AICDA, and of cell-surface molecules and miRNA that are associated with activated B cells. HAART only partially normalizes the immune system of treated HIV+ persons as they still show clear evidence for ongoing inflammation and immune activation in, even those who show complete suppression of HIV viremia. Together, this provides ample evidence to support the notion that chronic activation of B cells contributes to the genesis of B cell lymphomas.

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Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients

Abstract: A higher level of T-cell activation, Th1 cytokine serum concentration and markers of EBV replication, preceded B-cell lymphoma diagnosis. This may suggest that viral antigen stimulation is associated with the genesis of lymphoma in HIV-infected patients.

Cited by 12 publications

References 60 publications

Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Circulating Mediators of Inflammation and Immune Activation in AIDS-Related Non-Hodgkin Lymphoma

Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma

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