RESEARCH - Protective effect of noninherited maternal HLA-DR antigens on RA development

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Published online before print December 6, 2007, 10.1073/pnas.0710260104

PNAS | December 11, 2007 | vol. 104 | no. 50 | 19966-19970

BIOLOGICAL SCIENCES / IMMUNOLOGY

Protective effect of noninherited maternal HLA-DR antigens on

rheumatoid arthritis development

Anouk L. Feitsma,,, Jane Worthington, Annette H. M. van der Helm-van

Mil, Darren Plant, Thomson, Jennie Ursum||, Dirkjan van

Schaardenburg||, Irene E. van der Horst-Bruinsma, Jon J. van Rood,,

Tom W. J. Huizinga, René E. M. Toes, and René R. P. de Vries

Departments of Immunohematology and Blood Transfusion and

Rheumatology, Leiden University Medical Center, 2333 ZA, Leiden, The

Netherlands; Arthritis Research Campaign Epidemiology Unit, University

of Manchester, Manchester M13 9PT, United Kingdom; ||Jan van Breemen

Institute, 1056 AB, Amsterdam, The Netherlands; and Department of

Rheumatology, VU Medical Center, 1007 MB, Amsterdam, The Netherlands

Contributed by Jon J. van Rood, November 1, 2007 (received for review

July 23, 2007)

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.

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Read the entire article here:

http://www.pnas.org/cgi/content/full/104/50/19966

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