Rheumatoid arthritis

Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease

Arthritis RheumatolPublished Mechanistic study

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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