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
erythrocytes
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
(T232)
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.