A Potential Link Between HLA-DRB1/DQB1 Alleles and Response to Treatment in Rheumatoid Arthritis Patients

Area of Science:

• Immunogenetics
• Rheumatology
• Molecular Biology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
• Genetic factors, particularly human leucocyte antigen (HLA) alleles, play a significant role in RA susceptibility and progression.
• Anti-citrullinated peptide antibodies (ACPA) are key autoantibodies in RA, and their association with specific HLA alleles is well-established.

Purpose of the Study:

• To investigate the association of HLA-DRB1/-DQB1 alleles with ACPA status and treatment response in Iranian RA patients.
• To identify specific HLA alleles linked to disease activity and therapeutic outcomes in this population.

Main Methods:

• A cohort of 167 RA patients (114 good responders, 53 poor responders) and 330 healthy controls were analyzed.
• HLA-DRB1/-DQB1 alleles were determined using polymerase chain reaction with sequence-specific primers (PCR-SSP).
• Disease activity and treatment response were assessed using Disease Activity Score 28-joint (DAS28) scores over 9 months.

Main Results:

• HLA-shared epitope (SE) alleles were significantly more frequent in RA patients, particularly in poor responders and ACPA-positive individuals.
• Poor responders exhibited a higher prevalence of ACPA-positive and HLA-SE-positive (ACPA+SE+) genotypes compared to good responders.
• Specific HLA alleles, including DRB1*04:02, *04:04, *04:05, *10:01, DQB1*03:02, and *05:01, were more frequent in patients, while others like DRB1*04:01, *11:01, *13:01, and DQB1*06:03 were less frequent compared to controls.

Conclusions:

• The study suggests a strong relationship between HLA-SE alleles and ACPA development in RA.
• Specific HLA alleles are associated with differential treatment responses in RA patients.
• These findings underscore the importance of HLA genotyping in understanding RA pathogenesis and predicting therapeutic outcomes.