Immunogenetic and immunologic markers of early rheumatoid arthritis. RADIKAL program first stage results

Abstract

Objective. To assess frequency of immunogenetic (HLA-DRB I allels) and immunologic - anti-cyclic citrullinated peptide antibodies (ACCP), IgM rheumatoid factor (RF) - parameters and their significance as markers of early rheumatoid arthritis (RA). Material and methods. HLA-DRB 1 alleles, ACCP and IgM RF were evaluated in 95 pts with early RA who fulfilled ACR criteria 1987 with disease duration 2 years or less. In 85,3% of them disease duration was <12 months. 135 blood donors without autoimmune diseases and relevant compromised inheritance. Basic low-resolving oligo-typing of HLA- DRB 1 gene and high-resolving oligo-typing of HLA-DRB 1*04 alleles was performed with multiplex polymerase chain reaction. ACCP2 and IgM RF levels were evaluated by immunoenzyme assay and nephelometric immunoassay with commercial kits. Results. Early RA group showed higher frequency of HLA-DRB 1 allele than control group (45,3% and 15,6% respectively, OR=4,5, 95% Cl 2,3-8,7). *05, *06 and *07 alleles in RA group were significantly less frequent than in control. *0401 allele was most frequent (25,3%) among HLA-DRB 1*04. Double dose SE+/SE+ (double set of any from *01,*0401, *0404, *0405, *0408, *10) was revealed in 33,7% of RA group pts and in 5,2% of cases in control group (OR=9,3, 95% Cl 3,7-24,6, p=lxl0 7). Absence of SE alleles (SE-/ SE-) in RA group was negatively associated with RA development (OR=0,28, 95% Cl 0,20, 5). In RA pts homozygote *0401/*0401 genotype was significantly more frequent among SE+/SE+ genotypes than in control group (17,8% and 1,5% respectively, OR=14,5, 95% Cl 3,1-93,4, p<0,0001). In RA group ACCP diagnostic level was revealed in 60,0% of cases, IgM RF — in 71,6% of cases. Most close relationship existed between ACCP and RF (r =0,66, p<0,05), less prominent — between SE and ACCP (r s=0,34, p<0,05). Correlation relationship between SE and RF was not revealed. In presence of at least one SE allele RF concentration was 280,4±414,3 lU/ml, in absence — 83,1 + 176,1 lU/ml (p<0,01). ACCP level in SE presence and absence was 56,2±44,6 lU/ml and 27,5±41,2 IU/ml respectively (p<0,01). Conclusion. HLA-DRB 1 (SE+) allele, ACCP and RF are significant markers of early RA development risk but ACCP and RF have diagnostic significance.