Antibodies reactive to Plasmodium falciparum serine repeat antigen in children with Burkitt lymphoma from Ghana

Abstract

The role of protective immunity to Plasmodium falciparum (Pf) malaria in Burkitt lymphoma (BL) is unknown. We investigated the association between BL and antibodies reactive to SE36 antigen, a recombinant protein based on Pf-SERA5 gene, targeted by protective malaria immune responses. Cases were children (0–14 years) enrolled at the Korle-Bu Teaching Hospital, Accra, Ghana, during 1965–1994 with BL confirmed by histology or cytology (92% of cases). Controls were healthy appearing children enrolled contemporaneous to the cases from the nearest neighbor house to the case house age- and sex-frequency matched to the cases. Anti-SE36 IgG antibodies were measured using enzyme-linked absorbent immunoassays (ELISA). SE36 titers were estimated by extrapolating ELISA optical density (OD) readings to a standard fitting curve. Anti-SE36 titers were log-transformed for analysis. Odds ratios (OR) and 2-sided 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. The mean log endpoint dilution titers were 0.63 logs lower in cases than in controls (8.26 [SD 1.68] versus 8.89 [SD 1.75], Student’s t-test, P=0.019). Lower titers were observed in cases than controls aged 0–4 years (P=0.05) and in those aged 5–14 years (P=0.06). Low and medium tertiles of anti-SE36 IgG antibodies were associated with increased OR for BL ([OR 1.67, 95% CI 1.21–2.31] and [OR 1.33, 95% CI 0.96– 1.86], respectively, Ptrend =0.002) in analyses adjusting for age, sex, calendar period, and test plate. Our findings suggest that compared to similarly aged children enrolled from the same community, children with BL in Ghana have lower antibodies to SE36 antigen.

Endemic Burkitt lymphoma is associated with strength and diversity of Plasmodium falciparum malaria stage-specific antigen antibody response

“…After adjusting for sex, age, calendar-year period, inclusion in the previous SE36 study, 17 and all antibody results, eBL was inversely associated with anti-SE36 IgG1 seropositivity (aOR: 0.37; 95% CI 0.21-0.64; P , .001) and positively associated with anti-HRP-II IgG3 seropositivity (aOR 1.60; 95% CI 1.08-2.36; P 5 .019; Table 2). eBL was unrelated to anti-MSP-1 IgG3 seropositivity (P 5 .982) and unrelated to anti-6NANP IgG3 seropositivity (P 5 .844).…”

“…The low, medium, and high categories were defined using tertile cutoff points for the specific antibody among healthy controls with results equal or greater than the LOQ. The antigen-specific antibody ORs were adjusted for sex, age group (3-year bands), calendar year of enrollment, inclusion in the previous SE36 study, 17 and each other. The antigen-specific antibody results were considered a priori to be both exposures and potential confounders of each other.…”

Meeting the challenge of hematologic malignancies in sub-Saharan Africa

“…46 Elevated levels of nonprotective whole schizont antibodies, reflecting malaria-related immune activation, have been demonstrated among children with BL in Malawi and Uganda, 47,48 whereas protective antibodies against Plasmodium falciparum serine repeat antigen have been associated with lower BL risk in Ghana. 49 A clear etiologic link has not been established, yet P falciparum induces polyclonal expansion of B cells, impairs EBV-specific T-cell immune responses, 50 and may preferentially stimulate EBV replication and expansion of EBV-positive B-cell expression by its cysteine-rich interdomain region 1␣, 51 all of which suggest a possible etiologic role. Alternatively, malaria transmission is influenced by pesticides, bed-nets, sociocultural practices, and other ecologic factors, which may modulate BL risk by affecting immune responses to EBV or malaria, or by influencing additional cofactors, such as intestinal parasites.…”

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

“…The high BL incidence in areas with holoendemic Plasmodium falciparum suggests a possible link between malaria infection and BL in equatorial Africa, where the disease is termed endemic BL (eBL) (9-11). Epidemiological studies have suggested that the risk of eBL is highest during childhood when exposure to malaria peaks as measured by antibody levels and that the risk diminishes as children acquire antimalarial immunity and thereby gain immunological control of the blood stage parasites (12-15). …”