Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development.
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 DERAA (i.e., HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302, and *1304) are associated with protection from RA. It has been proposed that not only inherited but also noninherited HLA-antigens from the mother (NIMA) can influence RA-susceptibility. Up to now, no protective NIMAs were described. Here, we studied whether DERAA-containing HLA-DRB1-alleles as NIMA are associated with a protective effect. One hundred seventy-nine families were studied, 88 from the Netherlands and 91 from the United Kingdom. The frequency of DERAA-containing HLA-DRB1-alleles of the Dutch mothers (16.1%), but not of the fathers (26.2%), was lower compared with the general Dutch population (29.3%; P = 0.02). This was replicated in the English set of patients and controls (P = 0.01). Further, of all families, 45 contained at least one DERAA-negative child with RA and at least one DERAA-positive parent. The odds for the DERAA-negative RA patients of having a DERAA-positive mother was significantly lower compared with having a DERAA-positive father (OR 0.25; P = 0.003). These data show a protective NIMA-effect in a human autoimmune disease and indicate that a DERAA-positive mother can transfer protection against RA to her DERAA-negative child.
Feitsma
Anouk L
AL
Departments of Immunohematology and Blood Transfusion and Rheumatology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. a.l.feitsma@lumc.nl
Worthington
Jane
J
van der Helm-van Mil
Annette H M
AH
Plant
Darren
D
Thomson
Wendy
W
Ursum
Jennie
J
van Schaardenburg
Dirkjan
D
van der Horst-Bruinsma
Irene E
IE
van Rood
Jon J
JJ
Huizinga
Tom W J
TW
Toes
René E M
RE
de Vries
René R P
RR
D000409:Alanine / Q000235:genetics; D000483:Alleles; D001120:Arginine / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001224:Aspartic Acid / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D000939:Epitopes / Q000235:genetics; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics / Q000502:physiology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011446:Prospective Studies
D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; D000409:Alanine