Identification of host–pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank

Abstract

Certain infectious agents are recognised causes of cancer and other chronic diseases. To understand the pathological mechanisms underlying such relationships, here we design a Multiplex Serology platform to measure quantitative antibody responses against 45 antigens from 20 infectious agents including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as Chlamydia trachomatis, Helicobacter pylori and Toxoplasma gondii, then assayed a random subset of 9695 UK Biobank participants. We find seroprevalence estimates consistent with those expected from prior literature and confirm multiple associations of antibody responses with sociodemographic characteristics (e.g., lifetime sexual partners with C. trachomatis), HLA genetic variants (rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies) and disease outcomes (human papillomavirus-16 seropositivity with cervical intraepithelial neoplasia, and EBV responses with multiple sclerosis). Our accessible dataset is one of the largest incorporating diverse infectious agents in a prospective UK cohort offering opportunities to improve our understanding of host-pathogen-disease relationships with significant clinical and public health implications.

Sero-prevalence of 19 infectious pathogens and associated factors among middle-aged and elderly Chinese adults: a cross-sectional study

“…The prevalence of pathogens tends to vary greatly between and within populations and is often associated with disparities in socioeconomic status, household crowding, breastfeeding practices, food production practices and environmental factors such as climate. 5 Although many sero-epidemiological studies of major infectious pathogens have been undertaken, [6][7][8][9] they have tended to cover a single pathogen [6][7][8] or involve populations in high-income countries. 9 In China, although several nationwide surveys have previously reported on the prevalence of some major pathogens (eg, HBV, HCV), [10][11][12] there is limited contemporary data about the sero-prevalence of many other pathogens and their relevance for major NCDs beyond certain cancers.…”

“…5 Although many sero-epidemiological studies of major infectious pathogens have been undertaken, [6][7][8][9] they have tended to cover a single pathogen [6][7][8] or involve populations in high-income countries. 9 In China, although several nationwide surveys have previously reported on the prevalence of some major pathogens (eg, HBV, HCV), [10][11][12] there is limited contemporary data about the sero-prevalence of many other pathogens and their relevance for major NCDs beyond certain cancers. Moreover, few studies in China or elsewhere have systematically examined the sero-prevalence of multiple pathogens in the same population, which could provide important data about pathogen burden and the joint effects of different pathogens on disease aetiology.…”

“…The multiplex serology panel used in the present study was based on that developed for the UK Biobank, 9 with certain relevant modifications. More H. pylori antigens were included in the CKB panel and a few pathogens were removed taking their prevalence into account.…”

“…More H. pylori antigens were included in the CKB panel and a few pathogens were removed taking their prevalence into account. 9 The CKB panel measured antibody levels against 43 antigens from 19 infectious pathogens (see details in online supplemental table 1) including hepatitis B (HBV) and hepatitis C (HCV) viruses; HPV-16 HPV-18; herpes simplex viruses 1 and 2 (HHV-1 and HHV-2); varicella zoster virus (VZV); EBV; human CMV; HHV-6 and HHV-7; BK (BKV), JC (JCV) and Merkel cell (MCV) polyomaviruses; HIV; human T lymphotropic virus (HTLV); H. pylori; Chlamydia trachomatis and Toxoplasma gondii. Of these 19 pathogens, 8 (HBV, HCV, HIV, HTLV, H. pylori, HPV-16, HPV-18 and EBV) are classified as group I human carcinogens by the International Agency for Research on Cancer (IARC).…”

“…16 To define overall sero-positivity for a pathogen, antigen-specific sero-positivity results were subsequently combined using published algorithms (see details in online supplemental table 1 and figure 2). 9 For 100 (5%) of these participants, plasma samples collected at the two subsequent resurveys were also assayed to assess the consistency of sero-status (seroconversion and sero-reversion rates) measurements over a period of time.…”