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Morbidity does not influence the T-cell immune risk phenotype in the elderly: Findings in the Swedish NONA Immune Study using sample selection protocols
Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
Institute of Gerontology, School of Health Sciences, Jönköping, Sweden.
Department of Clinical Chemistry, Hospital of Ryhov, Jönköping, Sweden.
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2003 (English)In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 124, no 4, 469-476 p.Article in journal (Refereed) Published
Abstract [en]

A critical issue in our understanding of ageing and the immune system refers to the health status of the population from which inferences are drawn. The commonly used SENIEUR protocol, selecting individuals representing 'normal ageing' has recently been under debate because a substantial amount of individuals with various health problems are excluded. The aim of the present study was to investigate the influence of morbidity on immune parameters and to evaluate the associations with the T-cell immune risk phenotype (IRP), related to cytomegalovirus (CMV) seropositivity by applying the SENIEUR protocol and the OCTO-Immune protocol in the unselected population based sample (n = 138) of oldest-olds, participating in the Swedish NONA Immune Study. The SENIEUR protocol excluded over 90% of the sample whereas the OCTO-Immune protocol excluded almost 65% of the sample. Three independent groups, very healthy (SENIEUR), moderately healthy (OCTO-Immune) and frail (non-SENIEUR/non-OCTO-Immune) were created. Flow cytometry studies on lymphocyte sub-populations revealed no significant difference in CD4/CD8 ratio, CD3+CD4-CD8+, CD3+CD4+CD8-, CD8+CD57+CD28-, CD8+CD56+CD57- or CD8+CD56+CD57+ between the very healthy, moderately healthy and the frail subsamples. Our findings indicate that morbidity does not significantly influence the T-cell immune risk profile in the elderly, and we suggest the inclusion of broader samples in future immunogerontological studies.

Place, publisher, year, edition, pages
Elesvier , 2003. Vol. 124, no 4, 469-476 p.
Keyword [en]
Elderly, Selection, Health status, Lymphocyte subsets, CD8, CMV
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-26438DOI: 10.1016/S0047-6374(03)00024-1Local ID: 10981OAI: diva2:246987
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2010-04-07
In thesis
1. The Immune System in the Oldest-Old: Clinical and Immunological Studies in the NONA Immune Cohort
Open this publication in new window or tab >>The Immune System in the Oldest-Old: Clinical and Immunological Studies in the NONA Immune Cohort
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The oldest-old (people aged 80 or older) constituted 5 % of the population in Sweden in 2000, an increase from 1.5 % fifty years earlier. The immune system undergoes dramatic changes at high age, sometimes referred to as “immunosenescence”. However, the natures of these changes, and in particular, their clinical consequences are incompletely understood. In a previous longitudinal study, a set of immune parameters were identified and termed immune risk phenotype (IRP) because of an association with increased mortality. The IRP consists of changes in the T lymphocyte compartment, in particular an inverted CD4/CD8 ratio. The IRP was found to be associated with cytomegalovirus (CMV) infection, which through expansions of cytolytic anti-viral CD8 cell responses was ascribed a role in the development of IRP. The general aim of this thesis was to increase the knowledge of changes in the immune system and their clinical consequences in the oldest-old. The population-based random sample of the longitudinal NONA-Immune Study (n = 138, mean age 90 years at baseline) was used for all investigations.

In paper I, the effects on sample size of various exclusion protocols for immune studies of the elderly was examined. The commonly used SENIEUR protocol, selecting individuals representing ‘normal ageing’, excluded 90 % of nonagenarians. Based on different protocol criteria, individuals were grouped into ‘very healthy’, ‘moderately healthy’ or ‘frail’. The prevalence of CMV was similar across the groups. Further, differentiated CD8 populations associated with CMV, i.e. those expressing CD56, CD57 and CD45RA while lacking expression of CD27 and CD28, were equally distributed across the groups of the oldest-old, but were, as expected, significantly increased in the elderly compared to a middle aged control group. The findings showed that lymphocyte subsets associated with IRP might serve as significant biomarkers of ageing independent of the overall health status, also supporting the notion that immunological studies of the oldest-old should be done in population-based non-selected populations.

The IRP and the presence of low-grade inflammation, for example increase of   IL-6 in plasma, constitute major predictors of 2-year mortality in the oldest-old. In paper II, the CD4/CD8 ratio and IL-6 were found to predict 97 % of observed survival and 57 % of deaths over 2 years. The impact of IRP and IL-6 on 2-year survival was independent of age, sex and several diseases. The longitudinal design allowed temporal evaluations, suggesting a sequence of events starting with IRP and leading to inflammation in the decline state.                                      Four-year mortality in the oldest-old (paper III) was found to be mainly related to markers of inflammation and IRP. Individuals with both inverted CD4/CD8 ratio and high IL-6 level had significantly higher 4 year mortality (82 %) compared to individuals with CD4/CD8 ratio ³ 1 and low IL-6 level (29 %) at baseline. The presence of IRP and increased IL-6 level showed some associations with presence of diseases; in particular, IL6 was associated with the presence of cognitive impairment. However, despite being strong predictors of mortality, IRP and IL-6 could not be linked to any specific cause of death, probably due to the multi-factorial nature of these factors.                                                                                                                             The prevalence of antinuclear antibodies (ANA) in the oldest-old was higher compared to younger controls (paper IV). The difference across age was most pronounced in men, showing low levels at younger age, whereas the prevalence among the oldest-old men reached a similar level as in women. There was no association between the presence of ANA and IRP, CMV status or health status in the oldest-old.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 75 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1172
Elderly, selection, health status, lymphocyte subsets, CD8, CMV, cytomegalovirus, immune risk, immune risk phenotype, IRP, T-cells, interleukin 6, IL-6, survival, mortality, antinuclear antibodies, ANA, ageing, immunosenescence
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-54672 (URN)978-91-7393-429-9 (ISBN)
Public defence
2010-04-23, Originalet, Qulturum, Hus B4, Länssjukhuset Ryhov, Jönköping, 13:00 (Swedish)
Available from: 2010-04-07 Created: 2010-03-31 Last updated: 2011-02-23Bibliographically approved

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Nilsson, Bengt-OlofErnerudh, Jan
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Infectious DiseasesFaculty of Health SciencesClinical ImmunologyDepartment of Clinical Immunology and Transfusion Medicine
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