The combined impact of persistent infections and human genetic variation on C-reactive protein levels

Abstract

Multiple human pathogens establish chronic, sometimes life-long infections. Even if they are often latent, these infections can trigger some degree of local or systemic immune response, resulting in chronic low-grade inflammation. There remains an incomplete understanding of the potential contribution of both persistent infections and human genetic variation on chronic low-grade inflammation. We searched for potential associations between seropositivity for 13 persistent pathogens and the plasma levels of the inflammatory biomarker C-reactive protein (CRP), using data collected in the context of the UK Biobank and the CoLaus|PsyCoLaus Study, two large population-based cohorts. We performed backward stepwise regression starting with the following potential predictors: serostatus for each pathogen, polygenic risk score for CRP, as well as demographic and clinical factors known to be associated with CRP. We found evidence for an association between Chlamydia trachomatis (P-value = 5.04e-3) and Helicobacter pylori (P-value = 8.63e-4) seropositivity and higher plasma levels of CRP. We also found an association between pathogen burden and CRP levels (P-value = 4.12e-4). These results improve our understanding of the relationship between persistent infections and chronic inflammation, an important determinant of long-term morbidity in humans.

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths

“…They maintain a persistent infection by manipulating diverse aspects of host immune function [ 32 ]. The ensuing background level of multiple layers of immune manipulation have been linked to chronic mental and physical diseases including autoimmunity [ 33 , 34 , 35 , 36 , 37 ], increased speed of ageing [ 38 , 39 , 40 , 41 ], and chronic inflammation [ 42 ]. Pathogen burden is highest among the most disadvantaged social groups [ 43 ]—who also experience lower lifespan.…”

“…The human microbiome within the skin, digestive tract, respiratory tract, and reproductive tract are complex microbial communities with an important role in the maintenance of overall physical and mental health, and are extensively involved in pathogen-related diseases [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. These microbiomes seemingly communicate with each other and the immune system [ 79 ].…”