Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

Nagu, Tumaini; Aboud, Said; Rao, Martin; Matee, Mecky; Axelsson, Rebecca; Valentini, Davide; Mugusi, Ferdinand; Zumla, Alimuddin; Maeurer, Markus

doi:10.1016/j.ijid.2017.01.022

Cited by 14 publications

(17 citation statements)

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“…The association of active pulmonary TB with raised HCMV IgG levels was in contrast to findings of a hospital-based study where HCMV-specific T-cell responses in a whole blood assay were found to be lower in TB patients who died when compared to TB patients who survived [ 46 ]. In this hospital-based study, HCMV responses were likely a general indictor of ‘immune fitness’ and therefore predictive of patient survival.…”

Section: Discussioncontrasting

confidence: 58%

Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort

et al. 2018

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Human cytomegalovirus (HCMV) infection has been associated with increased mortality, specifically cardiovascular disease (CVD), in high-income countries (HICs). There is a paucity of data in low- and middle-income countries (LMICs) where HCMV seropositivity is higher. Serum samples from 2,174 Ugandan individuals were investigated for HCMV antibodies and data linked to demographic information, co-infections and a variety of CVD measurements. HCMV seropositivity was 83% by one year of age, increasing to 95% by five years. Female sex, HIV positivity and active pulmonary tuberculosis (TB) were associated with an increase in HCMV IgG levels in adjusted analyses. There was no evidence of any associations with risk factors for CVD after adjusting for age and sex. HCMV infection is ubiquitous in this rural Ugandan cohort from a young age. The association between TB disease and high HCMV IgG levels merits further research. Known CVD risk factors do not appear to be associated with higher HCMV antibody levels in this Ugandan cohort.

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Section: Discussioncontrasting

confidence: 58%

Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort

et al. 2018

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“…Anti-CMV/EBV immune responses may not only indicate (viral) target-specific cellular immune responses; impaired immune responses to both or either pathogen often reflects immune dysfunction [ [43] , [44] , [45] , [46] ]. In contrast, strong “intact” immune responses indicate ‘immune-fitness', as demonstrated in patients with pulmonary tuberculosis: well-preserved anti-CMV/EBV IFN-γ responses of PBMCs correlate with better survival following standard drug therapy [ 47 ]. Thus, it is plausible to conclude that amplification of clinically relevant T-cell responses to TLGEFLKLDRERAKN with IL-2/IL-15/IL-21, makes this cytokine combination a strong candidate to expand antigen-specific T-cells for adoptive immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme

et al. 2018

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PurposeWe investigated serum cytokine and T-cell responses directed against tumour-associated antigens (TAAs) in association with survival of patients with glioblastoma multiforme (GBM).Patients and MethodsPeripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A). Patients were followed-up for at least 1000 days post-surgery. Survivin protein and gene expression in resected GBM tumour tissue were confirmed by immunohistochemistry and real-time polymerase chain reaction, respectively. Antigen-specific T-cell responses were gauged by ICS (intracellular cytokine production). Associations between patient survival and immunological reactivity patterns were analysed using univariate and multivariate statistics.ResultsApproximately 2% of patients with GBM and 18% of patients with non-GBM glioma, were alive beyond 1000 days of surgery. Univariate analysis indicated that the combination of three cytokines (IL-4/IL-5/IL-6, p = .0022; IFN-γ/TNF-α/IL-17A, p = .0083) but not a ‘partial’ combination of these cytokines, the IFN-γ immune response to EBV-EBNA-1 (p < .0001) as well as T-cell responses to the survivin97–111 peptide (p = .0152) correlated with longer survival among patients with GBM. Multivariate analysis identified survivin97–111-directed IFN-γ production with IL-2/IL-15/IL-21 conditioning (p = .024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (p = .003) as independent predictors of survival.ConclusionSerum cytokine patterns and lymphocyte reactivity to survivin97–111, particularly with IL-2, IL-15 and IL-21 conditioning may be instrumental in predicting survival among patients with GBM. This has implications for clinical follow-up of patients with GBM and the targeted development of immunotherapy for patients with CNS tumours.

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“…This indicates cellular immunity level and its predominance over the humoral link. Probably, therefore, in many cases, the acute form of the EBV infection ends with a rapid and, as a rule, complete recovery [12][13].…”

Section: Resultsmentioning

confidence: 99%

Features of Cytokine Status in Patients With Chronic Ebv-Infections

Kolesnyk

Sorokina

Malanchuk

et al. 2018

The Journal of v. N. Karazin Kharkiv National University, Series "Medicine"

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Infections caused by EBV are the most common and occupy an important place in the structure of herpes aetiology diseases. The purpose of this work was to study the characteristics of the cytokine status in patients with chronic EBV infection, depending on the level of viral replication. We examined 78 patients with chronic EBV infection, the main clinical manifestations of which were various immunopathological and immunodeficiency states: Group I – with low, Group II – with medium, Group III - with a high degree of viral replication. The Tiff method was used using the Vector-Best reagent kits (Novosibirsk, Russia) to study the cytokine profile in the serum of patients with EBV infection. The determination of alpha and gamma fractions of serum interferon was carried out using the ELISA method by means of the ProCon IF2 plus reagent kit manufactured by Protein Contour LLC (St. Petersburg, Russia). As a result of a study of the cytokine status in patients with chronic EBV infection, it was found that in all three groups there was a significant increase in both pro-inflammatory (IL-1β, IL-6, TNF-α) and antiinflammatory cytokines (IL-10, IL 4, TGFβ1). However, anti-inflammatory cytokinemia was more compensated in group I patients compared with patients in groups II and III. A decrease in IFN-α and IFN-γ was detected in all patients with chronic EBV infection while studying the interferon status. A correlation was found between the level of viral replication and a decrease in the level of IFN-α and IFN-γ. The identified features of the cytokine status in patients with chronic EBV infection can be used to optimize therapy and help develop a differentiated approach to the immunocorrection of these patients, depending on the level of viral replication.

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Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

Cited by 14 publications

References 10 publications

Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort

Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort

Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme

Features of Cytokine Status in Patients With Chronic Ebv-Infections

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