Serologic markers of viral infection and risk of non‐Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore

Abstract

Incidence rates of non-Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre-diagnostic blood and NHL risk in East Asians. We conducted a nested case-control study of 214 NHL cases and 214 matched controls from three population-based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead-based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA-D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10-3.81; p = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96-4.89; p = 0.008) Epstein-Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus-6 (HHV-6) antigen (OR = 1.85, 95% CI = 1.04-3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV-HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV-6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

“…The seroprevalence of HHV-6A is unknown. However one study of Chinese individuals put the prevalence at 11% of controls [ 36 ]. One feature of all herpesviruses is that they can establish a lifelong persistent infection termed latency [ 37 ].…”

“…For example, HHV-6A reactivation has been found in patients with multiple sclerosis (MS) [ 51 ] and HIV infection [ 52 ] and HHV-6B reactivation has occurred in amnesia [ 53 ] and hepatitis [ 54 ]. The virus can also reactivate in the presence of malignant and non-malignant diseases [ 55 ] and HHV-6A antibodies are a risk factor for non-Hodgkin lymphoma [ 36 ].…”

Human Herpesvirus 6 and Malignancy: A Review

“…Standing alone, these PCR-based studies have not provided overly compelling evidence for or against a cooperative relationship in lymphomagenesis. In a recent case-control study of 214 NHL cases and 214 matched controls from three population-based prospective cohorts, seropositivity for HHV-6A immediate-early 1 protein (IE1A), but not HHV-6B IE1, was significantly associated with a greater risk of developing NHL of any type (OR 1.85, 95% CI 1.04–3.29) ( 147 ). However, levels of antibodies against EBV proteins ZEBRA and EA-D were slightly correlated with IE1A seropositivity, and the correlation between HHV-6A IE1A and NHL development was somewhat weaker after adjusting for these EBV-specific antibodies, suggesting that HHV-6A activity may interact with EBV and increase the risk of NHL.…”

Seropositivity of selected chronic infections and different measures of obesity

“…A Luminex 200 analyzer (Luminex Corp., Austin, TX, USA) then distinguished between the bead type and consequently the bound antigen as well as quantified the amount of bound serum antibody as the median fluorescence intensity (MFI) of at least 100 beads per type per serum. All assays were previously described and validated, and MFI values were dichotomized into seropositive and seronegative using previously defined standard cut-offs [15][16][17]. According to these standard definitions, infection status was defined as positive when exceeding a specific minimum number of antigens.…”