Causal Relationships between Circulating Immune Cell Traits and the Risk of Rheumatoid Arthritis and Osteoarthritis:...

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Rheumatoid arthritis (RA) and osteoarthritis (OA) are common chronic joint diseases with immune system involvement.
• The precise causal links between immune cell characteristics and the development of RA and OA are not fully understood.

Purpose of the Study:

• To investigate the potential causal relationships between circulating immune cell phenotypes and the risk of developing rheumatoid arthritis and osteoarthritis.
• To utilize a bidirectional two-sample Mendelian randomization approach to explore these genetic associations.

Main Methods:

• Employed a bidirectional two-sample Mendelian randomization (MR) study design.
• Utilized genome-wide association study (GWAS) summary statistics for immune cell traits, RA, and OA.
• Applied five MR methods, including inverse-variance-weighted (IVW), with FDR correction and MR-Egger intercept tests for pleiotropy assessment.

Main Results:

• CD27 expression on memory B cells showed a significant negative causal relationship with rheumatoid arthritis risk (P < 0.001) after FDR adjustment.
• Human leukocyte antigen (HLA)-DR expression on CD14+ monocytes was negatively associated with osteoarthritis risk (P < 0.001).
• Rheumatoid arthritis was negatively associated with HLA-DR expression on myeloid dendritic cells, though horizontal pleiotropy was detected.

Conclusions:

• This Mendelian randomization study establishes causal links between specific immune cell traits and the pathogenesis of rheumatoid arthritis and osteoarthritis.
• Findings enhance our understanding of the immunological underpinnings of these prevalent joint disorders.