HLA-DR Genotypes in Familial Rheumatoid Arthritis: Increased Frequency of Protective and Neutral Alleles in a Multicase Family

SZILVIA ZSILÁK, JÁNOS GÁL, LÁSZLÓ HODINKA, KATALIN RAJCZY, ATTILA BALOG, SÁNDOR SIPKA, SÁNDOR BARÁTH, ANIKÓ KAPITÁNY, ERIKA ZILAHI, and ZOLTÁN SZEKANECZ

ABSTRACT.

Objective. We describe a unique family where each of the 5 siblings in the second generation has rheumatoid arthritis (RA). Two other members of the family have RA and systemic lupus erythematosus (SLE), respectively. No members of previous generations in the family had documented inflammatory arthritis. Due to the suspected genetic predisposition, HLA-DR genotypes were determined in the affected siblings and their parents, children, and grandchildren. We investigated the possible role of various HLA-DR alleles in the evolution of RA in this multicase family.

Methods. HLA-DRB1* alleles were determined by polymerase chain reaction using the sequence-specific primer–Olerup method.

Results. The most common alleles in the 6 persons with RA were HLA-DRB1*07 and DRB1*15, which are known to be protective and neutral in RA. No patient or family member carried any HLA-DR4 alleles.

Conclusion. HLA-DRB1*07 and DRB1*15 alleles are thought to be protective or neutral in RA. However, the majority of RA patients in the family and nearly half of all family members carried these alleles, suggesting a role of these genotypes in susceptibility to RA. No RA patient in this family carried HLA-DR4 alleles. Thus, in our rare family with 6 RA cases, an unexpected genetic background may be involved in the increased susceptibility to inflammatory arthritis. (J Rheumatol 2005;32:2299-302)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
FAMILY TREE
HLA-DRB1 ALLELES
SHARED EPITOPE

---

From the National Institute of Rheumatology and Physiotherapy, Budapest; Department of Rheumatology, County Hospital, Kecskemét; National Medical Center, Institute of Haematology and Immunology, Budapest; Department of Microbiology and Immunobiology, University of Szeged, Szeged; and Regional Laboratory of Immunology and Division of Rheumatology, Third Department of Medicine, University of Debrecen Medical Center, Debrecen, Hungary.

S. Zsilák, MD, National Institute of Rheumatology and Physiotherapy, Department of Rheumatology, County Hospital, Kecskemét; J. Gál, MD, Department of Rheumatology, County Hospital, Kecskemét; L. Hodinka, MD, PhD, National Institute of Rheumatology and Physiotherapy; K. Rajczy, PhD, National Medical Center, Institute of Haematology and Immunology; A. Balog, MD, Department of Microbiology and Immunobiology, University of Szeged; S. Sipka, MD, DSci; S. Baráth; A. Kapitány; E. Zilahi, PhD, Regional Laboratory of Immunology, University of Debrecen Medical Center; Z. Szekanecz, MD, PhD, Division of Rheumatology, University of Debrecen Medical Center.

Address reprint requests to Dr. S. Zsilák, National Institute of Rheumatology and Physiotherapy, 38-40 Frankel Leó str, Budapest, H-1023, Hungary. E-mail: zsilaksz@freemail.hu

Accepted for publication July 26, 2005.

---