Immunoglobulin KM and GM gene polymorphisms modify the clinical presentation of primary Sjögren's syndrome.
OBJECTIVE
To investigate whether polymorphism of immunoglobulin (Ig) genes affects susceptibility to or severity of primary Sjogren'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 beta2-microglobulin (beta2-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 beta2-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.
Pertovaara
Marja
M
Department of Internal Medicine and the Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland. marja.pertovaara@pshp.fi
Hurme
Mikko
M
Antonen
Jaakko
J
Pasternack
Amos
A
Pandey
Janardan P
JP
D015415:Biomarkers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007129:Immunoglobulin Gm Allotypes; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012470:Salivary Glands, Minor / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology
D015415:Biomarkers; D007129:Immunoglobulin Gm Allotypes; D007142:Immunoglobulin gamma-Chains; D007145:Immunoglobulin kappa-Chains