Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease
Authors' conclusion
T cell-driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA.
Study context
- Population
- Lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early rheumatoid arthritis (RA) patients and anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing RA7,680 single B cells
- Participants
- 3 vs 9
- Comparison
- ACPA+ individuals at risk of RA and untreated early RA vs ACPA- individuals
- At risk of RAn = 3
- Early RAn = 9
- Outcome
- Lung-resident B cells in BAL (single-cell phenotyping and monoclonal antibody re-expression)
Methodological detailssingle-cell B cell sequencing, monoclonal antibody re-expression
- Single-cell B cell sequencing
- Monoclonal antibody re-expression
Main finding
As reported in the abstract
- Highly mutated citrulline-autoreactive clones from different memory B cell subsets, in at-risk individuals and early RA
- 7
- Frequent mutation-induced N-linked Fab glycosylation sites in lung IgG variable gene transcripts from ACPA+ individuals, often in framework 3
- P < 0.001
- Lung ACPAs binding activated neutrophils (1 at risk of RA, 1 early RA)
- 2
Original publication
Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease. Arthritis Rheumatol. Published 3 August 2023. doi:10. 1002/ art. 42549
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