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Abstract: HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied focusing on an elderly HIV-infected population.The objectives of the study were to assess 29 blood markers of immune activation and inflammation using an ultrasensitive technique, in HIV-infected patients aged ≥75 years with no or 1 comorbidity (among hypertension, renal disease, neoplasia, diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and osteoporosis), in comparison with age-adjusted HIV-uninfected individuals to identify whether biomarkers were associated with comorbidities. Wilcoxon nonparametric tests were used to compare the levels of each marker between control and HIV groups; logistic regression to identify biomarkers associated to comorbidity in the HIV group and principal component analysis (PCA) to determine clusters associated with a group or a specific comorbidity.A total of 111 HIV-infected subjects were included from the Dat'AIDS cohort and compared to 63 HIV-uninfected controls. In the HIV-infected group, 4 biomarkers were associated with the risk of developing a comorbidity: monocyte chemoattractant protein-1 (MCP-1), neurofilament light chain (NF-L), neopterin, and soluble CD14. Six biomarkers (interleukin [IL]-1B, IL-7, IL-18, neopterin, sCD14, and fatty acid-binding protein) were significantly higher in the HIV-infected group compared to the control group, 11 biomarkers (myeloperoxydase, interleukin-1 receptor antagonist, tumor necrosis factor receptor 1, interferon-gamma, MCP-1, tumor necrosis factor receptor 2, IL-22, ultra sensitivity C-reactive protein, fibrinogen, IL-6, and NF-L) were lower. Despite those differences, PCA to determine clusters associated with a group or a specific comorbidity did not reveal clustering nor between healthy control and HIV-infected patients neither between the presence of comorbidity within HIV-infected group.In this highly selected geriatric HIV population, HIV infection does not seem to have an additional impact on age-related inflammation and immune disorder. Close monitoring could have led to optimize prevention and treatment of comorbidities, and have limited both immune activation and inflammation in the aging HIV population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients with chronic kidney disease (CKD) are more prone to develop premature age-related diseases. Data on immune senescence are scarce in CKD populations, except in end-stage renal disease and dialysis. We designed a longitudinal prospective study to evaluate immune senescence at different CKD stages and its influence on CKD patient outcomes., Methods: Clinical and biological data collections were performed on 222 patients at different CKD stages [1-2 (n = 85), 4 (n = 53) and 5 (n = 84)]. Immune senescence biomarkers were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, γH2A.X) or by quantitative polymerase chain reaction [relative telomere length (RTL)] on peripheral blood mononuclear cells and analysed according to CKD stages and outcomes., Results: CKD was associated with an increase in immune senescence and inflammation biomarkers, as follows: low thymic output (197 ± 25 versus 88 ± 13 versus 73 ± 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of terminally differentiated T cells (CD8+CD28-CD57+) (24 ± 18 versus 32 ± 17 versus 35 ± 19%) restricted to cytomegalovirus-positive patients, telomere shortening (1.11 ± 0.36 versus 0.78 ± 0.24 versus 0.97 ± 0.21 telomere:single copy ratio) and an increase in C-reactive protein levels [median 2.9 (range 1.8-4.9) versus 5.1 (27-9.6) versus 6.2 (3.4-10.5) mg/L]. In multivariate analysis, shorter RTL was associated with death {hazard ratio [HR] 4.12 [95% confidence interval (CI) 1.44-11.75]}. Low thymic output was associated with infections [HR 1.79 (95% CI (1.34-9.58)] and terminally differentiated CD8+ T-cell expansion with a risk of cardiovascular events [CEs; HR 4.86 (95% CI 1.72-13.72)]., Conclusion: CKD was associated with premature immune ageing. Each of these alterations increased the risk of specific age-related diseases, such as RTL and death, thymic function and infections and terminally differentiated CD8+ T-cell expansion and CEs., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts., Methods: Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method., Results: Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups., Conclusion: Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs., (Copyright © 2020. Published by Elsevier Ltd.)

Prospective studies have indicated an age-related impairment of the immune response. Carotenoids have been hypothesised to enhance immune cell function. The aim of the present study was to describe the age-related effects and the impact of in vivo dietary carotenoid depletion and repletion on specific and non-specific immunity. A total of ninety-eight healthy male subjects (aged 20-75 years) received a carotenoid-depleted diet for 3 weeks and were then supplemented daily for 5 weeks with 30 mg β-carotene, 15 mg lycopene and 9 mg lutein. Blood samples were collected at study entry, after depletion and supplementation, and biomarkers of immune status were determined. We found that serum IgA levels were positively correlated with ageing. Lymphocyte phenotyping indicated an increase with age in the memory T-helper cell subpopulation (CD4⁺CD45RO⁺) concomitantly with a decrease in naive T-helper cells (CD4⁺CD45RA⁺). A significant increase in the natural killer cells subpopulation and a small decrease in B lymphocytes were also observed, especially for the oldest volunteers. From ex vivo cell function exploration, a positive correlation was observed between age and IL-2 production of phytohaemagglutinin-stimulated lymphocytes. Neutrophils' bactericidal activity was significantly impaired with age (from 50 years) and was modulated by carotenoid status. An age effect was found on neutrophils' spontaneous migration but not on directed migration. Immune response in healthy human subjects is mostly affected by age rather than by dietary carotenoid depletion and repletion. Even in carefully selected healthy volunteers, some age-related immune changes occur predominantly from 50 years onwards. This immunosenescence could generate a loss in the immune system adjustment capacity.

Introduction: Immunosenescence embraces the whole of age-induced changes observed in the immunomodulatory functions of a living organism, and is mostly characterized by a decrease in cell-mediated immunity and important modifications of the immunological repertoire. The impact of the pathology on ageing immunity is poorly understood and few data are available on the immunological status of old polypathological patients., Methods: We report the results of a prospective study aiming at characterizing several established immunological parameters in patients of 75 years old or more, and admitted for diverse pathologies in a unit of acute geriatric ward., Results: Among the 51 included patients (35 women and 16 men), 90% displayed poly-pathologies. We found a prevalence of 86% of immunological abnormalities, with lymphopenia among 41% of the patients (<1500/mm(3)) and abnormal lymphocytes phenotypes among 95% of the oldest patients (>85 years). A strong skewing towards memory T lymphocytes (CD45RO+) over naive T lymphocytes (CD45RA+) was found in 80% of the cases and inverted CD4/CD8 T cells ratio was observed in 12% of our patients. Vitamin D insufficiency (<30ng/ml), which is frequent among the patients (94%), is a predictive factor for T and B cell lymphopenia., Conclusion: Immunological abnormalities are frequent in this frail population and lymphopenia, in particular, could constitute a reinforcing factor of fragility. Vitamin D deficiency could also affect elderly patients' immunity., (Copyright © 2010. Published by Elsevier SAS.)

Objective: The prevalence of some autoantibodies in the elderly population has been reported to be greater than in younger controls. The prevalence of ANCA has been shown to be low in a generally healthy population, but has not been established in the elderly. Thus, the presence of ANCA in elderly patients might not have the same clinical significance as in younger people. The aim of this study was to evaluate the prevalence of ANCA in elderly subjects., Patients and Methods: Serum samples from 137 subjects (96 females, 41 males; mean age = 82.2 years +/- 6.97 SD) were evaluated. Criteria for exclusion included suspected or established systemic vasculitis, connective tissue or neoplastic diseases, acute infection, HIV infection, current therapy with corticosteroids or cytotoxic drugs, and recent blood transfusion. ANCA were detected by indirect immunofluorescence on ethanol-fixed normal human neutrophils. Fluorescence patterns were classified as c-ANCA, p-ANCA or nuclear. Sera exhibiting p-ANCA or nuclear fluorescence were further tested by IIF on formalin-acetone fixed normal human neutrophils. Sera whose reaction pattern was cytoplasmic were considered as positive for "true" pANCA. Additionally, sera were tested for the presence of antinuclear antibodies (IIF), anti-double-stranded DNA (enzyme immunoassay) and IgM rheumatoid factors (enzyme immunoassay)., Results: The prevalence of c-ANCA was 0% (95% CI = 0-2.66), the prevalence of p-ANCA was 2.2% (95% CI = 0.45-6.3), and the prevalence of "true" p-ANCA was 0.73% (95% CI = 0.02-4). The prevalence of ANA, anti ds-DNA and RF were respectively 38%, 3.6%, and 11.7%., Conclusion: The prevalence of ANCA is not increased in elderly people. Thus, the presence of ANCA in elderly subjects may have the same clinical significance as in younger people.

To date, only one seroepidemiological survey, carried out in Japan, gave a strong indication that dogs may be naturally infected by the influenza C virus, long considered to be exclusively human. In the present work, 134 serum samples were collected during the winter of 1988/89 from dogs aged 6 months to 16 years in northern France. Samples were tested for the presence of antibodies to influenza C virus by both haemagglutination inhibition (HI) and ELISA. Using antibody absorption by staphylococcal protein A, we demonstrated the specificity of the results. In 62% of cases, the results were identical using the two methods. Significant HI activity was found in 32% of the 134 tested sera and titres ranged from 20 to 320. Of the sera tested, 42% were positive by ELISA and titres ranged from 500 to 8,000. The discordant results are discussed. The population tested was divided into five age groups: less than 4 years, 4 to 6 years, 7 to 9 years, 10 to 11 years and greater than 12 years. The distribution of antibodies in the tested canine population, in contrast to that of humans, did not show a significant degree of association with age.

We analyzed sera from 102 subjects older than 65 years of age with no clinical evidence of autoimmune disorders, inflammatory diseases or pharmacological interventions. Positive titers for antinuclear antibodies were found in 18.6%, anti-smooth muscle fibre in 16.6%, and rheumatoid factor in 11.8%. These values were significantly higher than those of a control group of healthy younger adults (p < 0.0001). Anti mitochondrial antibodies were present in 1% (NS). Thus, a greater proportion of autoimmune phenomena is demonstrated in the elderly.