ABSTRACT
The genetic background of juvenile rheumatoid arthritis [JRA] in Egyptian children is understudied. The association between class II human leukocyte antigen [HLA] and RA in adults had been reported in different ethnic populations. To detect the frequency prevalence of HLA-DRB1 genes, and to study the influence of such alleles on JRA susceptibility or protection among a group of Egyptian children having polyarticular onset JRA. Also, to clarify the genetic contribution of the shared epitope [SE] positive alleles in relation to JRA severity and progression. Genotyping of HLA-DRB1 alleles were analyzed by polymerase chain reaction- sequence-specific primer amplification and allele specific probing technique in 60 JRA Egyptian children and 50 healthy children serving as controls. Measurement of bone mineral density [BMD using single energy quantitative computed tomography [SEOCT] was done to all patients and controls. The strength of the association of these alleles with JRA susceptibility, severity [clinical and radiological], and progression was expressed as relative risk estimated by odd ratio [OR]. The most frequent DRB1 specificities among JRA were *04 [allele frequency = 25.2%], *14 [20.7%], and *01[10.8%] compared to *08 [25.6%] and *04 [16.9%] among controls. In a logistic regression model, both DRB1 *04, and *14 alleles were significantly associated with JRA susceptibility while *08 allele was protective. Among JRA, the most common SE-containing DRB1 haplotypes were *1001 [5.4%], *0101 *0401, *0404, and *1402 [4.5% for each]. SE sequences were present in 40% of patients compared to 10% of controls [P=0.0001]. SE was present in homozygous state in 22% of patients. Furthermore, in a logistic regression model, the likelihood of having JRA was 29.6-fold higher among homozygote SE [P=0.002], compared to 1.94-fold higher among heterozygote SE [P=0.06]. The SE sequence [QKRAA, QRRAA and RRRAA] was found in [10%, 41.6%, and 10% respectively in JRA versus 2%, 8%, and 2% respectively in controls]. The carriage of [SE+/+] alleles encoding glutamine [0] at beta 70 [Q70 + or high risk SE] were associated with the greatest risk of JRA, while possession of alleles encoding aspartic [D] at beta 70 [D70 + or low risk SE] were associated with the lowest risk [OR 0.46 and 0.64, respectively] There were significant associations between disease clinical severity, radiological progression, and reduced BMD and the presence of [*04] and [*01] alleles. Our findings confirm the association of DRB1 *04 and *14 alleles with JRA susceptibility, and DRB1*08 with protection. A double allelic dose of SE particularly *04 and *01 alleles may contribute to the risk of developing severe forms of JRA, and are strong determinant of disease progression and aggressiveness. We recommended that DRB1 genotyping is one of the parameters to be taken into account to predict the course and prognosis of JRA and to aid in selecting children who deserve early aggressive therapy, thereby helping to prevent some of the associated morbidity and mortality. Further wide scale prospective hospital-based controlled studies are warranted to verify this conclusion and extend preliminary results