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

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


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. 

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. 

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. 

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. 

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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