Table 1: Summary of the mechanisms of protection to malaria, and their possible association with rheumatoid arthritis pathogenesis.

FactorEvolutionary modificationResistance mechanism to malariaModified immunological pathwayPossible role in rheumatoid arthritis pathogenesis

Duffy antigenDuffy-negative alleleLack of expression of chemokines receptorChemokines sinkAmplification of immune response and lack of chemokines depuration

-globinSickle hemoglobinSuppression of parasite growth in red cells and enhanced splenic clearance of parasitized
Reduced parasite cytoadherenceUnknown.
Increased expression of VCAM-1, E-selectin, and ICAM-1?
Decrease of immune complexes clearance by asplenia.

FcγIIBSubstitution of
threonine for isoleucine
at position 232
in the transmembrane
domain of FcγRIIB
Increased clearance of malarial parasites
Phagocytosis of plasmodium falciparum-infected erythrocytes. Differentiation of B lymphocytes
The abnormal function leads to an increase in immune reactivity mainly mediated by B lymphocytes

CR1Polymorphisms of CR1 are involved in the amount of protein expression in the red cell membrane.Reduced ability of P. falciparum-infected CR1-deficient red blood cells to form rosettesReduced ability of P. falciparum-infected CR1-deficient red blood cells to form rosettes, and less severe diseaseCR1 is a complement regulatory protein, responsible for removing immune complexes from the circulation. Decreased of immune complexes clearance

NK1.1(−) andNK1.1(+)
subsetsofTCR (int) cells
???Autoantibody production?

GYPCGYPC-deficient erythrocytes Protection against EBA-140-mediated invasion by P. falciparum parasites Binding receptor-parasite protein?

CR1: complement receptor 1; GYPC: glycophorin C.