Protection against rheumatoid arthritis by HLA: nature and nurture.
Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70-74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA" (ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA"-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA"-containing HLA-DRB1 alleles are compared.
Feitsma
A L
AL
Department of Rheumatology, LUMC, Leiden, The Netherlands. A.L.Feitsma@lumc.nl
van der Helm-van Mil
A H M
AH
Huizinga
T W J
TW
de Vries
R R P
RR
Toes
R E M
RE
D020816:Amino Acid Motifs / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D046528:Chimerism; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male
D005819:Genetic Markers; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains