title: Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development.
abstract: 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.
authors: Departments of Immunohematology and Blood Transfusion and Rheumatology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. a.l.feitsma@lumc.nl
authors: Anouk L
authors: AL
authors: Feitsma
authors: Jane
authors: J
authors: Worthington
authors: Annette H M
authors: AH
authors: van der Helm-van Mil
authors: Darren
authors: D
authors: Plant
authors: Wendy
authors: W
authors: Thomson
authors: Jennie
authors: J
authors: Ursum
authors: Dirkjan
authors: D
authors: van Schaardenburg
authors: Irene E
authors: IE
authors: van der Horst-Bruinsma
authors: Jon J
authors: JJ
authors: van Rood
authors: Tom W J
authors: TW
authors: Huizinga
authors: René E M
authors: RE
authors: Toes
authors: René R P
authors: RR
authors: de Vries
mesh_terms: 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
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; D000409:Alanine