A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells

Abstract

Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27− memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.

Maternal and cord blood BAFF and APRIL levels during pregnancy

“…Strikingly, both cord BAFF and cord APRIL levels were considerably greater than the corresponding maternal third‐trimester serum BAFF and serum APRIL levels. These findings are consistent with, and expand upon, previous reports of circulating BAFF levels being greater in newborns than in their mothers 14–16 …”

“…These findings are consistent with, and expand upon, previous reports of circulating BAFF levels being greater in newborns than in their mothers. [14][15][16] This relative abundance of BAFF and APRIL in the neonatal circulation could reflect, at least in part, a paucity of B-lineage cells that express receptors for BAFF and/or APRIL, thereby reducing the physiologic "sinks" for these cytokines. Alternatively, but not mutually exclusively, active production of BAFF and APRIL by placental elements [17][18][19] may be contributory.…”

Osteopontin and malaria: no direct effect on parasite growth, but correlation with P. falciparum-specific B cells and BAFF in a malaria endemic area

“…Since both BAFF and OPN have roles in B cell differentiation, we compared OPN concentrations with BAFF concentrations, recently reported for these individuals [ 42 ]. OPN concentration in infants were positively correlated with BAFF concentrations at birth (r= 0.36, P = 0.003), 6 months (r= 0.29, P = 0.035) and 9 months (r= 0.53, P <0.001) (Fig.…”

“…In the present study, we measured longitudinal variations in concentrations of OPN in mothers and their infants and monitored them over nine months. We also determined correlations between concentrations of OPN and P. falciparum -specific B cell subsets, and antibodies to P. falciparum schizont extract as well as concentrations of BAFF [ 21 , 42 ]. Additionally, we investigated the effect of OPN on parasitic growth using an in vitro invasion assay.…”

Immunosuppression in Malaria: Do Plasmodium falciparum Parasites Hijack the Host?

“…Despite being more highly expressed during infection, BAFF is not able to support antigen-secreting cell (ASC) survival by binding to TACI and BCMA receptors in pediatric malaria [111], since the form of BAFF found in circulating serum is not its ligand [118,119]. Additionally, BAFF levels have also been negatively associated with Pf -specific and total IgG + subsets of memory B cells in infants [120]. By contrast, APRIL, which is over BAFF the main ligand of those two receptors, is highly produced in Pf infections [121].…”