Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
The Comprehensive B Cell Profiling Analysis of a Multicenter SLE Cohort.
Jung1, John, Biear1, Jamie, Huang1, Youqun, Neary1, Bridget, Marin1, Elides, Hossler1, Jennifer, Palmer1, Elise
B cell abnormalities in Systemic Lupus Erythematosus (SLE) are well-established contributors to disease pathogenesis. Past limitations such as pauci-color flow cytometry have limited a full characterization of this multifactorial disease. This study utilizes several multicolored flow cytometry panels to render a high-resolution footprint of the B cell profiles linked with comprehensive clinical parameters to identify distinct B cell signatures in SLE.
PBMCs were isolated and analyzed by flow cytometry from Healthy Controls (HC) (n=36) and SLE patients (n=161). B cell subsets were identified using the following markers: IgD, CD19, CD27, CD38, CD24, CXCR3, CD21, CD24, CD95, MitoTracker Green, CD10, IgM, CD23. SLE patients met ACR criteria for the classification of SLE, and were sub-categorized based on primary clinical manifestation. Disease activity and flares were measured by SELENA-SLEDAI and physician global assessment. All clinical and experimental data were imported into a customized database where multivariate methods were used to seek natural divisions based on the B cell profiles and relationship to clinical parameters.
Our initial analyses show pronounced heterogeneity in SLE subjects. Multidimensional analysis of our multicolor panels can identify a total of 330 B cell subsets of which 132 demonstrate abnormal behavior with significantly different frequencies found between HC, SLElow (SLEDAI<=4), and SLEhi (SLEDAI>4) disease activity (p<0.05). SLE patients have a significant expansion of CD27- memory B cells and a contraction of unswitched memory subsets relative to HC subjects (p<0.05). Further characterization of memory B cells reveals additional signatures of active disease characterized by expansions of CD21low, CD24low, CXCR3hi, and CD95hi that correlate with higher number of autoantibodies, lower C3/C4 levels, higher disease activity, and flares (p<0.0005). Detailed analysis of the IgD+CD27- subsets show B cell subset shifts where overall the true naïve B cells contract and the transitional B cell compartments expand when compared to healthy controls (p<0.005). High dimensional multi-parameter analysis identifies multiple clusters of SLE subjects that can be sub-classified based on their B cell profiles and show similar clinical features. Further novel-analysis tools including heat-map displays and Principle Component Analysis confirm the added value of refined B cell phenotyping for superior segregation of HC and SLE subclasses.
Collectively, this study demonstrates that while SLE patients have variable B cell profiles, immune-profiling has the ability to identify clusters of SLE. Two year longitudinal studies of these subjects are currently under way to clarify whether the signatures corresponding to the different disease clusters have subset-specific changes to disease activity and predictive of disease progression. These profiles will be useful in understanding disease. Careful immunological studies of patients with SLE will increase our understanding of multiple aspects of human B cell biology and will be critical to providing the framework for the design and evaluation of current and future B cell targeted therapies.
To cite this abstract, please use the following information:
Jung, John, Biear, Jamie, Huang, Youqun, Neary, Bridget, Marin, Elides, Hossler, Jennifer, et al; The Comprehensive B Cell Profiling Analysis of a Multicenter SLE Cohort. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1767