Abstract: Immunoglobulin KM and GM Gene Polymorphisms Modify the Clinical Presentation of Primary Sjögren's Syndrome

Immunoglobulin KM and GM Gene Polymorphisms Modify the Clinical Presentation of Primary Sjögren's Syndrome

MARJA PERTOVAARA, MIKKO HURME, JAAKKO ANTONEN, AMOS PASTERNACK, and JANARDAN P. PANDEY

ABSTRACT.

Objective. To investigate whether polymorphism of immunoglobulin (Ig) genes affects susceptibility to or severity of primary Sjögren's syndrome (pSS).

Methods. Ig gene kappa (KM) and gamma (GM) polymorphisms were analyzed by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) based method in 65 Finnish Caucasian patients with pSS and in 66 healthy controls matched for sex, ethnic origin, and area of residence. Clinical and immunological data on the pSS patients were analyzed in relation to Ig genotypes.

Results. The genotype frequencies of Ig KM and GM genes did not differ between pSS patients and controls. Anti-SSB antibodies were encountered significantly more frequently in pSS patients carrying the KM1 allele than in those without (100% vs 48%, p = 0.016). The pSS patients with the KM1 allele had several signs of immunologically active disease: they had significantly higher erythrocyte sedimentation rate, serum IgA, serum ß₂-microglobulin (ß₂-m), and plasma IgG1 concentrations than patients without this allele. The pSS patients carrying the GM z allele had a milder form of pSS than those without this determinant. They had less severe labial salivary gland histological findings (grade 3-4 in 60% vs 93%, p = 0.004) and lower plasma IgG3 and serum ß₂-m concentrations than those without GM z allele.

Conclusions. Ig KM and GM genes do not contribute to susceptibility to pSS. The Ig KM1 allele is associated with several markers of immunologically active disease, whereas the Ig GM z allele is associated with milder pSS. (J Rheumatol 2004;31:2175-80)

Key Indexing Terms:

IMMUNOGLOBULIN
GENE POLYMORPHISM
PRIMARY SJÖGREN'S SYNDROME

From the Department of Internal Medicine and the Centre for Laboratory Medicine, Tampere University Hospital; the University of Tampere Medical School, Tampere, Finland; and the Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.

Supported in part by funds from the US Department of Energy cooperative agreement DE-FC09-02CH11109 and by grants from the Medical Research Fund of Tampere University Hospital, Tampere, Finland, and the Scandinavian Rheumatology Research Foundation.

M. Pertovaara, MD, PhD, Department of Internal Medicine, Tampere University Hospital; M. Hurme, MD, PhD, Professor, Centre for Laboratory Medicine, Tampere University Hospital and the University of Tampere Medical School; J. Antonen MD, PhD; A. Pasternack MD, PhD, Professor, Department of Internal Medicine, Tampere University Hospital and University of Tampere Medical School; J.P. Pandey, PhD, Professor, Department of Microbiology and Immunology, Medical University of South Carolina.

Address reprint requests to Dr. M. Pertovaara, Department of Internal Medicine, Section of Rheumatology, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland. E-mail: marja.pertovaara@pshp.fi

Submitted February 24, 2004; revision accepted June 21, 2004.