Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases - particularly systemic lupus erythematosus

Czech version

Authors: M. Fojtíková
Authors‘ workplace: Revmatologický ústav Praha
Published in: Čes. Revmatol., 20, 2012, No. 1, p. 30-38.
Category: Review

Overview

Background:
Several factors like genetic susceptibility are required for the development of systemic rheumatic diseases. Prolactin (PRL) is an effective immunomodulator which supports the development of autoimmunity.

Objectives:
1. To detect the immunogenetic background (HLA class I and II alleles and alleles of microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene (MIC-A)) in SLE and PsA.2. To detect PRL levels in serum and synovial fluid with regard to clinical and laboratory activity of RA. 3. To examine the role of the functional polymorphism -1149G/T SNP of extrapituitary promoter of PRL gene in the development and phenotype of SLE, RA, PsA, SSc and inflammatory myopathies.

Methods:
Genetic analyses were performed in patients with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47), DM (n=68) and 123 healthy individuals using PCR-SSP (HLA class I and II), PCR-fragment analysis (MIC-A) and PCR-RFLP (-1149 G/T SNP PRL). In 29 RA and 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay.

Results:
1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in the Czech population. The allele MIC-A5.1 was increased in SLE compared to controls (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 significantly increases the risk for the development of SLE, pc <0.000001; OR 9.71. The allele HLA-Cw*0602 occurs more frequently in PsA with psoriasis type I compared to controls, pc <0.05; OR 3.33. 2. Serum and synovial fluid PRL levels were increased in RA (299.55±27.28 and 338.85± 33.49 mIU/l, respectively) compared to OA (230.59±16.61 and 245.97±21.88 mIU/l, respectively, both p<0.05). Synovial fluid PRL levels correlate with DAS-28 (p=0.010) and serum PRL levels correlate with structural damage (p=0.014). 3. Genotype GT -1149 G/T SNP PRL is more frequent in RA than in controls, pc =0.039; OR 1.82. Genotype GG is more common in patients with onset of SLE at the age of 21 – 40 years compared to other disease onsets, pc =0.023; OR 2.94. Similarly, the TT genotype seems to be rare in SSc with disease onset after 45th year of age compared to patients with disease onset prior 45 years of age, pc =0.02; OR 0.13.

Conclusion:
This is the first immunogenetic study in two severe rheumatic diseases - SLE and PsA in the Czech population. We detected that the allele MIC-A5.1 incerases the risk for the development of SLE in HLA-DRB1*03 individuals. The allele HLA-Cw*0602 is a risk factor for PsA with psoriasis type I. PRL modulates the course of systemic rheumatic diseases: PRL reflects the activity and severity of RA, and alleles of -1149G/T SNP PRL gene show differences associated with the age at disease onset of SLE and SSc.

Key words:
systemic lupus erythematosus, psoriatic arthritis, polymorphism, allele, gene, prolactin

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Czech Rheumatology

2012 Issue 1