Computational Biologist Massachusetts Gen. Hosp. Cambridge, Massachusetts, United States
Disclosure(s):
Wamia Said: No financial relationships to disclose
Introduction/Rationale: Lyme arthritis (LA) resolves after antibiotics in most individuals, but a minority develop a chronic arthropathy despite clearance of Borrelia burgdorferi (Antibiotic-Refractory LA, ARLA). This condition is clinically distinct from acute LA and is marked by oligoclonal T cell & excessive Th1 responses. LA is influenced by genetic & clinical factors, but no biomarkers predict chronicity prior to antibiotics. Identifying patients at risk for ARLA can improve risk stratification & therapy. More broadly, understanding how excessive immune responses are controlled in most LA patients may reveal mechanisms of immune homeostasis.
Methods: We compared four patient groups: pre-antibiotic acute LA (n=5), pre-ceftriaxone (CTX) LA responders (n=5), pre-CTX LA who subsequently developed ARLA (n=7) and ARLA (n=5). Synovial fluid from donors was profiled by single-cell gene expression (scRNAseq), T-cell receptor sequencing, & surface protein expression (CITEseq). scRNAseq data was batch integrated and annotated. Logistic regression (MASC), partial least squares (OPLS), and CellPhoneDB analyses identified abundance shifts, outcome-related gene programs, and cell–cell interactions, respectively.
Results: We captured >500K cells, identifying diverse cell types including rare migratory dendritic cells and proliferative lymphocytes. ARLA showed enrichment of proliferative and Th1-like CD4+ T cells, consistent with its excessive immune response. Shared programs between ARLA and pre-CTX donors who developed ARLA, including distinct CD8+ T populations, suggest a baseline signature of future chronicity is detectable.
Conclusion: This is the first comparative multi-omic analysis across LA patient groups. It confirms that ARLA is a distinct immune process to pre-antibiotic LA and reveals baseline synovium differences between patients who resolve and who develop chronic disease. This aligns with previously described differences, but provides immunological context to such differences and a resource for developing biomarkers.
