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Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study.

ABSTRACT: The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1?, IL-6, IL-10, IFN?, and GM-CSF using a Luminex-based multiplex assay, and results were linked to data from the Danish National Prescription Registry. The filing of an antimicrobial prescription following c-aAb measurement was used as a proxy for impaired immunocompetence. We found that c-aAb against pro-inflammatory cytokines IFN? and GM-CSF tended to associate with increased risk of prescription filings in women, whereas antibodies against anti-inflammatory IL-10 were associated with a lower predicted risk of antimicrobial prescriptions, as well as higher self-perceived health scores. We also observed an association of cumulative c-aAb presence with prescription risk. Our data show that cytokine autoantibodies in healthy individuals associate with various proxies for immunomodulation, with the exact association dependent on the pattern of pro- or anti-inflammatory cytokines targeted. This suggests that c-aAb may express cytokine-modulatory properties in healthy individuals and may be critical to further investigate as biomarkers of immunodeficiency.

SUBMITTER: von Stemann JH

PROVIDER: S-EPMC7082412 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study.

von Stemann Jakob H JH Pedersen Ole B OB Hjalgrim Henrik H Erikstrup Christian C Ullum Henrik H Thørner Lise W LW Larsen Margit Ah MA Burgdorf Kristoffer S KS Sørensen Erik E Hansen Morten B MB Ostrowski Sisse R SR

Journal of clinical immunology 20200115 2

The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1α, IL-6, IL-10, IFNα, and GM-CSF using a Luminex-based multiplex assay, and results w ...[more]

PMID: 31940126

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Project description:BACKGROUND:Health-Related Quality of Life (HRQL) represent individuals' subjective assessment of their mental and physical well-being, and is highly predictive of future health. C-reactive protein (CRP) is a well-established marker of inflammation. Low-grade inflammation (LGI), defined as slightly increased CRP levels, is associated with increased risk of several diseases. LGI may reflect subclinical pathology, which could affect individual's subjective health assessment. This study aimed to examine whether LGI has an independent impact on self-reported health or rather is a mediator of a confounder in a large population of healthy individuals. METHODS:Plasma CRP levels were measured in 17,024 participants from the Danish Blood Donor Study (DBDS). All participants completed a standard questionnaire including smoking status, and the 12-item short-form health survey (SF-12), which is a widely used scale for HRQL. SF-12 is reported as a mental (MCS) and physical (PCS) score. The relationship between LGI (defined as a plasma CRP level between 3 mg/L and 10 mg/L) and MCS or PCS was explored by mediation analysis and adjusted multivariable linear regression analysis. Multiple imputation modelling was used to remedy missing values. The analyses were stratified according to sex and use of combined oral contraception (OC). RESULTS:In the study, 1,542 (10.3%) participants had LGI. PCS was associated with LGI in all strata, i.e. women using OC: RC = -0.36 points lower PCS in participants with LGI vs no LGI, CI: -0.94 to -0.19, women not using OC: RC = -0.63, CI: -1.05 to -0.21 and men: RC = -0.76, CI: -1.10 to -0.42. But LGI had no impact on MCS. Predictors of lower PCS included obesity, current smoking, and waist circumference in all strata. Physical activity in leisure time was the only factor positively associated with PCS. Age and physical activity in leisure time was associated with increased MCS in all strata whereas current smoking was the only strong predictor of a reduction in MCS. Only a small effect of smoking on PCS was mediated through LGI. CONCLUSION:In this population of healthy individuals, LGI had independent impact on lower self-rated physical health score in HRQL in both sexes, but was not associated with self-rated mental health score. A small and significant effect of smoking on physical health score was mediated through LGI.

Project description:A high number of somatic symptoms have been associated with poor health status and increased health care use. Previous studies focused on number of symptoms without considering the specific symptoms. The aim of the study was to investigate 1) the prevalence of 19 somatic symptoms, 2) the associations between the symptoms, and 3) the associations between the somatic symptoms, self-perceived health and limitations due to physical health accounting for the co-occurrence of symptoms. Information on 19 somatic symptoms, self-perceived health and limitations due to physical health was achieved from a population-based questionnaire survey of 36,163 randomly selected adults in the Capital Region of Denmark in 2006/07. Chain graph models were used to transparently identify and describe the associations between symptoms, self-perceived health and limitations due to physical health. In total, 94.9% of the respondents were bothered by one or more of the 19 somatic symptoms. The symptoms were associated in a complex structure. Still, recognisable patterns were identified within organ systems/body parts. When accounting for symptom co-occurrence; dizziness, pain in legs, respiratory distress and tiredness were all strongly directly associated with both of the outcomes (?>0.30). Chest pain was strongly associated with self-perceived health, and other musculoskeletal symptoms and urinary retention were strongly associated with limitations due to physical health. Other symptoms were either moderate or not statistically associated with the health status outcomes. Opposite, almost all the symptoms were strongly associated with the two outcomes when not accounting for symptom co-occurrence. In conclusion, we found that somatic symptoms were frequent and associated in a complex structure. The associations between symptoms and health status measures differed between the symptoms and depended on the co-occurrence of symptoms. This indicates an importance of considering both the specific symptoms and symptom co-occurrence in further symptom research instead of merely counting symptoms.

Dataset Information

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study.

Publications

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study.

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