Apoptosis and hِ-allels in juvenile rheumatoid arthritis

Abstract EN

Objectives: This study was conducted to determine HLA-DR alleles in juvenile rheumatoid arthritis (JRA) patients and controls.

Also, to assess apoptosis in JRA patients in comparison to normal individuals as well as find out whether there is any correlation between them.

Methods: We typed 60 JRA patients & 60 controls for HLA-DR1, DR2, DR4, DR5, DR6 and DR8 with serology (microcytotoxicity test).

HLA-DR subtypes were then analyzed by sequence specific primers polymerase chain reaction (SSP-PCR).

Apoptosis in JRA patients & controls was measured with preparation and culture of blood neutrophils.

The cells were incubated for 24, 48 and 72 hours in tissue culture medium.

Both morphology and DNA fragmentation was assessed and the percentage of neutrophil apoptosis in each culture determined.

Results: We found that HLA-DR8 antigen was increased significantly in JRA patients than controls (p<0.05 and Odd’s ratio= 2.02).

We observed that the frequency of DR8*0802 subtype was high among JRA patients and showed significant difference than controls (p<0.0001 and Odd’s ratio =8.11).

We also examined the association of HLA-DR8 with disease severity and activity.

There was no significant difference between the association of this subtype with disease parameters and laboratory findings.

There was a significant inhibition of neutrophil apoptosis in JRA patients in comparison to normal subjects (p<0.0001).

HLA-DR8 showed a significant association with apoptosis (p<0.0001).

We also observed a significant association between DRB1*08(0802) and apoptosis (p<0.0001).

Conclusions: These findings suggest that JRA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and HLA-DRB1 can be a useful prognostic factor for JRA and establish linkage and association between the major histocompatibility complex and JRA.

The mechanism of controlled cell death (apoptosis) plays an important role in the pathogenesis of JRA and could be targeted for new treatment strategies.