Relation of serum retinol to acute phase proteins and malarial morbidity in Papua New Guinea children

Background: Acute phase proteins (APPs) are associated with malaria- induced hyporetinemia (serum retinol <0.70 μmol/L); however, the degree of the association is not well documented. Objective: The association between malaria-induced hyporetinemia and APPs was assessed. Design: In a cross- sectional study, 90 children with serum retinol concentrations from <0.35 to >1.05 μmol/L were selected from children in a clinical trial of vitamin A supplementation. Serum was collected before treatment allocation. Retinol binding protein (RBP) concentrations were determined by radioimmunoassays, and transthyretin, α₁-acid glycoprotein (AGP), α₁-antichymotrypsin, C- reactive protein (CRP), haptoglobin, and albumin concentrations by radial immunodiffusion assays. Results: Children in the subsample had high rates of splenomegaly and Plasmodium-positive blood-smear slides (P < 0.01); AGP (Pearson's r = -0.40, P < 0.001) and CRP (r = -0.21, P = 0.04) were inversely correlated with retinol. The negative APPs RBP, transthyretin, and albumin were positively and significantly associated with retinol. All APPs, except β₁-antichymotrypsin, were significantly correlated with splenomegaly. Of the positive APPs, AGP correlated with CRP (r = 0.37, P < 0.001), indicating chronic inflammation. In a stepwise regression analysis, 73% of retinol's variability was explained by RBP and transthyretin. The model predicted that a 1-SD increase in RBP or transthyretin increases retinol by ≃0.38 or 0.47 μmol/L, respectively, whereas an equivalent increase in AGP decreases retinol by 0.12 μmol/L Conclusions: The RBP-transthyretin transport complex of retinol is not altered by inflammation. Positive APPs are useful markers of type and severity of inflammation; however, except for AGP, it is unlikely that they can correct for malaria-induced hyporetinemia.