Maternally Transferred Antibody Levels And Igg3 Hinge Region Length Polymorphisms In The Risk Of Clinical Malaria In Infants In A Birth Cohort At Kintampo, Ghana

ABSTRACT

Introduction: Plasmodium falciparum malaria remains a global public health threat especially for children under five years. Fetuses receive maternal immunoglobulins in utero by passive transfer and this is believed to protect infants at least for the first six months after delivery. IgG3 among the IgG subclasses is known to be more protective because of the long hinge region making the molecule flexible and easier to link antigens and Fc receptors for antigen elimination. However, there are hinge region polymorphisms among the IgG3 molecules that may have an impact on their protective potential.

Aim: This study investigated the relationship between maternally transferred total IgG (IgG) levels and their subclasses against GLURP R0 and MSP1-19. Also to investigate the role of infants’ IgG3 hinge region length polymorphisms in the risk of clinical malaria in a birth cohort at Kintampo, Ghana.

Methodology: Serum and blood blots samples with the clinical data of participants were taken from a previous birth cohort study conducted in Kintampo. Serum samples were taken from cord blood at birth (month 0), month 3 and month 6 from 202 infants for immunoglobulins level measurement against GLURP R0 and MSP1-19 using indirect ELISA. IgG with its subclasses were measured at month 0 and IgG3 levels measured at months 3 and 6. One hundred and forty blood blots were selected to determine infants’ IgG3 hinge region length polymorphisms using polymerase chain reaction (PCR).

Results: Among 202 infants, 112 (55.45%) were not protected from clinical malaria (presence of parasites and fever), 68 (33.66%) had asymptomatic parasitaemia (protected) and 22 (10.89%) had no parasites and no fever (indeterminate group). There were

significant differences in anti-GLURP R0 and anti-MSP1-19 total IgG levels at birth (p < 0.05) between protected and non-protected infants but not so for the subclasses. There was a sharp decrease in IgG3 levels against both antigens from month 0 to month 3.

Among the 138 infants whose IgG3 hinge region length polymorphisms (IgG3HRLPs) were genotyped, 93.33% had clinical malaria in first year of life. Four IgG3HRLP genotypes were found. The homozygote medium (MM) polymorphism had the highest frequency of 53.33%, followed by the homozygote long (LL) polymorphism with a frequency of 42.22%. The homozygote short (SS) and heterozygote long-medium (LM) polymorphisms were very few among these infants.

Conclusion: Maternally transferred anti-GLURP R0 and anti-MSP1-19 IgG levels at birth were associated with protection against clinical malaria in infants but the subclasses were not. Infants’ IgG3HRLPs was not associated with protection from clinical malaria after one year.