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Protection against rheumatoid arthritis by HLA: nature and nurture
  1. A L Feitsma1,2,
  2. A H M van der Helm-van Mil1,
  3. T W J Huizinga1,
  4. R R P de Vries2,
  5. R E M Toes1
  1. 1
    Department of Rheumatology, LUMC, Leiden, The Netherlands
  2. 2
    Department of Immuno- haematology and Blood Transfusion, LUMC, Leiden, The Netherlands
  1. Miss A L Feitsma, Department of Rheumatology, C1-R, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; A.L.Feitsma{at}


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.

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  • Competing interests: None.

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