Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation

Type I/II interferon in HIV-1-infected patients: expression in gut mucosa and in peripheral blood mononuclear cells and its modification upon probiotic supplementation

Expression of type I and II interferon (IFN) was evaluated in gut-associated lymphoid tissue (GALT) and peripheral blood mononuclear cells (PBMCs) of HIV-1-positive patients on long-term, suppressive, antiretroviral therapy before and after probiotic supplementation. IFNα subtypes and IFNβ were expressed at higher levels in GALT compared to PBMC, whereas an opposite trend of expression was recorded for IFNγ. An increase of IFNα6, IFNα10, IFNα14, IFNα17, and IFNα21 and a decrease of IFNγ were observed in both anatomical sites after probiotic supplementation

Kinetics of Torquetenovirus viremia in patients receiving solid organ transplantations

9nonenoneMaggi F.; M. Statzu; G. Bianco; C. Costa; D. Focosi; L. Macera; M. Pistello; R. Cavallo; G. AntonelliMaggi, F.; M., Statzu; G., Bianco; C., Costa; D., Focosi; L., Macera; M., Pistello; R., Cavallo; G., Antonell

Challenges in the management of HIV infection. Update on the role of probiotic supplementation as a possible complementary therapeutic strategy for cART treated people living with HIV/AIDS

Introduction: Recent insights show that gut-mucosal immunity and intestinal microbiota play a key role in the pathogenesis of HIV infection. Alterations in the composition of intestinal flora (dysbiosis) could be associated with an impaired intestinal epithelium barrier activity and an impaired mucosal immunity function, significantly contributing to microbial translocation which is considered a major driver of chronic immune activation. Areas covered: This article provides an overview on the novel trends in probiotic therapy application. A particular emphasis is addressed to the importance of probiotics as a novel strategy to attenuate or prevent gastrointestinal involvement and to improve gut-mucosal immunity in HIV-infected subjects. Therefore, opportunities, limits and methodological criticalities of supplementation with probiotic therapy are considered and analyzed. Expert opinion: Use of probiotics is emerging as a novel strategy to manage dysbiosis and gut-mucosal impairment, to reduce immune activation and to limit a number of non-AIDS-related disorders. However, despite the growing use of probiotic therapy, mechanisms by which oral bacteria intake exhibits its effects are strain-related and disease-specific, hence clinicians need to take these two factors into consideration when suggesting probiotic supplementation to HIV-infected patients

Increased IL-17 and/or IFN-γ producing T-cell subsets in gut mucosa of long-term-treated HIV-1-infected women

OBJECTIVE: The influence of sex on gut mucosal T-cell response in HIV-1 infection remains largely unknown. We explored whether the frequencies of interferon-γ and/or IL-17 producing naive, T central memory and T effector memory (TEM) CD4 (Th1, Th17) and CD8 T (Tc1, Tc17) cells measured in gut and peripheral districts differed between female and male HIV-1-infected patients. METHODS: Thirty long-term-treated HIV-1-infected individuals were enrolled. The frequencies of Th1, Th17, Tc1, Tc17-cell subsets (single and double) were evaluated by multiparametric flow cytometry in lamina propria lymphocytes and peripheral blood mononuclear cells (PBMC). RESULTS: A sex-based pattern was recorded in the differences of Th1, Th17, Tc1, Tc17-cell subset (single and double) frequencies between gut and peripheral blood. Female patients had stronger alterations in the gut mucosal T-cell repertoire, especially increased Th1, Th17, and Th1/Th17-cell subset frequencies, compared with the blood district than their male counterparts. Higher naive Tc1, Tc17, Tc1/Tc17, TEM Tc17, and TEM Tc1/Tc17 levels were also recorded in the gut mucosa than in the PBMC of HIV-1-infected women. Males and females also differed in their gut T-cell response, with women being characterized by higher Th1, Th17, Tc1, Tc17, and Th1/Th17 cells subset levels than men. By contrast, only TEM Th1/Th17 and TEM Tc17 in PBMC differed between males and females. CONCLUSION: Sex-based differences observed in the gut T-cell response of HIV-1-infected patients might contribute to the disease dimorphism

Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV-1-infected male patients

Given human immunodeficiency virus-1 (HIV-1)-infected patients have alterations in the type I interferon (IFN-I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN-I response and subclinical cardiovascular disease (CVD) association in HIV-1-infected patients. Transcript levels of IFN-α/β and IFN-stimulated gene 56 (ISG56) were evaluated by RT/real-time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV-1-positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima-media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti-HIV drugs (D:A:D) were also measured. Increased IFN-α, IFN-β, and ISG56 levels were observed in all HIV-1-infected males compared to healthy controls (p <.001 for all genes analyzed). HIV-1-infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p =.019), which was correlated with IFN-β and ISG56 levels. HIV-1-infected males with enhanced IFN-I levels and stenosis displayed a higher ASCVD calculated risk (p =.011) and D:A:D score (p =.004). Also, there was a trend toward higher IFN-α and ISG56 mRNA levels in HIV-1-positive patients with an increased cIMT (p >.05). Dysregulation of IFN-I response might participate in the pathogenesis of HIV-1-associated CVD

Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients

PURPOSE: To investigate the contribution of SAMHD1 to HIV-1 infection in vivo and its relationship with IFN response, the expression of SAMHD1 and IFN-related pathways was evaluated in HIV-1-infected patients. METHODS: Peripheral blood mononuclear cells (PBMC) from 388 HIV-1-infected patients, both therapy naïve (n = 92) and long-term HAART treated (n = 296), and from 100 gender and age-matched healthy individuals were examined. CD4+ T cells, CD14+ monocytes and gut biopsies were also analyzed in HIV-1-infected subjects on suppressive antiretroviral therapy. Gene expression levels of SAMDH1, ISGs (MxA, MxB, HERC5, IRF7) and IRF3 were evaluated by real-time RT-PCR assays. RESULTS: SAMHD1 levels in HIV-1-positive patients were significantly increased compared to those in healthy donors. SAMHD1 expression was enhanced in treated patients compared to naïve patients (p < 0.0001) and healthy donors (p = 0.0038). Virologically suppressed treated patients exhibited higher SAMHD1 levels than healthy donors (p = 0.0008), viraemic patients (p = 0.0001) and naïve patients (p < 0.0001). SAMHD1 levels were also increased in CD4+ T cells compared to those in CD14+ monocytes and in PBMC compared to those of GALT. Moreover, SAMHD1 was expressed more strongly than ISGs in HIV-1-infected patients and positive correlations were found between SAMHD1, ISGs and IRF3 levels. CONCLUSIONS: SAMHD1 is more strongly expressed than the classical IFN-related genes, increased during antiretroviral therapy and correlated with ISGs and IRF3 in HIV-1-infected patients