Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

TY - JOUR

T1 - Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

AU - Santaolalla, Aida

AU - Sollie, Sam

AU - Rislan, Ali

AU - Josephs, Debra H

AU - Hammar, Niklas

AU - Walldius, Goran

AU - Garmo, Hans

AU - Karagiannis, Sophia N

AU - Van Hemelrijck, Mieke

N1 - Funding Information: This work was supported by King's College London, Karolinska Institutet, Pancreatic Cancer Action and the Gunnar and Ingmar Jungner Foundation for Laboratory Medicine. The research was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London (IS-BRC-1215-20006). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors acknowledge support by Cancer Research UK (C30122/A11527; C30122/A15774); The Academy of Medical Sciences; the Medical Research Council (MR/L023091/1); Cancer Research UK King’s Health Partners Centre at King’s College London; CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587). The funding sources had no role in the design of this study and collection, execution, analyses, interpretation of the data, writing the manuscript or decision to submit results. Publisher Copyright: © 2021, The Author(s).

PY - 2021/9/6

Y1 - 2021/9/6

N2 - BACKGROUND: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions. From the AMORIS cohort, 5513 individuals were identified with baseline measurements of serum humoral immune [immunoglobulin G, A & M (IgG, IgA, IgM)] and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.RESULTS: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.CONCLUSIONS: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

AB - BACKGROUND: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions. From the AMORIS cohort, 5513 individuals were identified with baseline measurements of serum humoral immune [immunoglobulin G, A & M (IgG, IgA, IgM)] and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.RESULTS: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.CONCLUSIONS: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

UR - http://www.scopus.com/inward/record.url?scp=85114366724&partnerID=8YFLogxK

U2 - 10.1186/s12865-021-00448-2

DO - 10.1186/s12865-021-00448-2

M3 - Article

C2 - 34488637

SN - 1471-2172

VL - 22

SP - 61

JO - BMC Immunology

JF - BMC Immunology

IS - 1

M1 - 61

ER -