Contributions
Abstract: P340
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - MS Variants
Background: Neuromyelitis optica spectrum disorder (NMOSD) is a severe, recurrent autoimmune inflammatory disorder of the central nervous system (CNS) associated with a pathogenic antibody response against aquaporin-4 (AQP4). AQP4 serum titers, however, are a poor prognosticator of NMOSD disease activity. Biomarkers of NMOSD activity would be valuable for predicting treatment response.
Methods: We evaluated changes in pro-inflammatory, regulatory, and anergic B cell populations in NMOSD patients using fluorescence activated cell sorting (FACS). We obtained and purified peripheral blood B cells from active (< 1 month from acute clinical attack) and quiescent (> 90 days from acute clinical attack) AQP4-seropositive NMOSD patients. NMOSD patients were either untreated or naïve to B cell-depleting therapy. We determined the relative fractions of naïve, memory, double negative (DN), plasmablasts, B10 regulatory and anergic B cell subsets. Functional variants within the memory and double negative B cell populations were further assessed using surface and intracellular markers.
Results: The number of naïve, memory (CD27+IgD-), double negative (CD72-IgD-, DN) memory, B10 regulatory, and anergic B cells failed to distinguish active from inactive NMOSD patients. Cell surface markers of B cell activation (CD86, HLA-DR2, CD24, CD148) also failed to correlate with disease activity. We identified a novel B cell subset (CD11c+CxCR5-) within both the memory and DN memory B cell populations, that was significantly elevated in active NMOSD patients. This unique B cell subset expressed CD21, FcRL5, and the transcription factor T-bet.
Conclusions: Our studies have identified an expanded population of memory and DN memory B cells (CD11c+CxCR5-CD21+FcRL5+T-bet+) in active NMOSD patients. This population shares surface markers identical to B cells that are expanded in systemic lupus erythematosus patients. Fluctuations in circulating Tbet+ B cells may be a useful marker for monitoring NMOSD patients.
Disclosure: Funding: National Institutes of Health, Guthy Jackson Charitable Foundation. Disclosures: Jeffrey L. Bennett: Nothing to disclose; Jingyang Zhang: Nothing to disclose; Alanna Ritchie: Nothing to disclose; Gregory P. Owens: Nothing to disclose
Abstract: P340
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - MS Variants
Background: Neuromyelitis optica spectrum disorder (NMOSD) is a severe, recurrent autoimmune inflammatory disorder of the central nervous system (CNS) associated with a pathogenic antibody response against aquaporin-4 (AQP4). AQP4 serum titers, however, are a poor prognosticator of NMOSD disease activity. Biomarkers of NMOSD activity would be valuable for predicting treatment response.
Methods: We evaluated changes in pro-inflammatory, regulatory, and anergic B cell populations in NMOSD patients using fluorescence activated cell sorting (FACS). We obtained and purified peripheral blood B cells from active (< 1 month from acute clinical attack) and quiescent (> 90 days from acute clinical attack) AQP4-seropositive NMOSD patients. NMOSD patients were either untreated or naïve to B cell-depleting therapy. We determined the relative fractions of naïve, memory, double negative (DN), plasmablasts, B10 regulatory and anergic B cell subsets. Functional variants within the memory and double negative B cell populations were further assessed using surface and intracellular markers.
Results: The number of naïve, memory (CD27+IgD-), double negative (CD72-IgD-, DN) memory, B10 regulatory, and anergic B cells failed to distinguish active from inactive NMOSD patients. Cell surface markers of B cell activation (CD86, HLA-DR2, CD24, CD148) also failed to correlate with disease activity. We identified a novel B cell subset (CD11c+CxCR5-) within both the memory and DN memory B cell populations, that was significantly elevated in active NMOSD patients. This unique B cell subset expressed CD21, FcRL5, and the transcription factor T-bet.
Conclusions: Our studies have identified an expanded population of memory and DN memory B cells (CD11c+CxCR5-CD21+FcRL5+T-bet+) in active NMOSD patients. This population shares surface markers identical to B cells that are expanded in systemic lupus erythematosus patients. Fluctuations in circulating Tbet+ B cells may be a useful marker for monitoring NMOSD patients.
Disclosure: Funding: National Institutes of Health, Guthy Jackson Charitable Foundation. Disclosures: Jeffrey L. Bennett: Nothing to disclose; Jingyang Zhang: Nothing to disclose; Alanna Ritchie: Nothing to disclose; Gregory P. Owens: Nothing to disclose