Date: Sunday, November 5, 2017
Session Title: B Cell Biology and Targets in Autoimmune Disease Poster
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Lupus is a spectrum of disease with cutaneous lupus (CLE) without systemic features on one end and systemic lupus erythematosus (SLE) on the other. Among CLE subtypes, chronic cutaneous lupus (CCLE) is deemed less likely to be associated with systemic features. However, 10-20% CCLE will develop SLE throughout their disease course. Little is known regarding the immunological correlates to the disease progression, which we postulate may be accompanied by the emergence of SLE-associated B cell abnormalities. As an initial test for our hypothesis, we compared the B cell phenotypes in a cross-sectional analysis among patients with CCLE, SLE with or without CCLE.
Methods: Patients met SLICC and ACR criteria for the classification of CCLE and SLE. Frozen PBMCs were analyzed by flow cytometry from healthy controls (HC) (n=23) and patients with primary CCLE (n=60), SLE (n=58) or CCLE with SLE (n=42). B cell subsets were identified using the following markers: CD19, IgD, CD27, CD38, CD24, CD21, CD11c, 9G4, in addition to CD3 and live/dead staining as exclusion markers. Frequencies of the various B cell subsets were compared among the groups using ANOVA followed by Tukey’s multiple comparison statistical tests. To gain a global view of the changes in B cell homeostasis, an unsupervised hierarchical clustering analysis of the B cell profiles was carried out.
Results: Several B cell abnormalities have been shown in SLE patients compared to the healthy controls, including a contraction of IgD+CD27+ unswitched memory (USM) and an expansion of IgD–CD27– double negative (DN) cells. These observations are replicated in this study as well. Furthermore, within the DN population, a subset of cells with an activated phenotype (CD11c+CD21–, termed DN2) is significantly expanded in SLE compared to HC. Its counterpart in the IgD+CD27– naïve and transitional (N+T) compartment – the CD11c+CD21– activated naïve (aN) B cells – is also expanded in SLE, though not statistically different from HC. Interestingly, CCLE patients share with SLE the characteristic contraction of USM also seen in Sjogren’s and other autoimmune diseases, yet they do not exhibit the expansion of DN, activated DN2 and aN subsets. Instead, CCLE patients show an expansion of the early transitional (T1+T2) cells. Globally, an unsupervised hierarchical clustering analysis demonstrates the segregation of HC from SLE (with or without CCLE) on the basis of their B cell profiles. On the other hand, B cell profiles of CCLE patients are heterogeneous and interspersed between HC and SLE patients.
Conclusion: Cross-sectional analysis at baseline reveals that CCLE patients share some SLE abnormalities including contracted USM and expansion of early transitional B cells, but do not display expansions of activated mature B cells (both naïve and isotype switched DN cells), a phenotype that is frequently observed in SLE patients. Moreover, our study demonstrates that from a B cell standpoint, CCLE is a heterogeneous condition thereby opening the door to investigations of correlations between distinct B cell profiles and clinical variables and in particular, with progression to systemic disease. Confirmation awaits the longitudinal follow-up of these patients over the next years.
To cite this abstract in AMA style:Wei C, Hill A, Smith K, Sanz I, Lim SS, Drenkard C. B Cell Abnormalities in Patients with Chronic Cutaneous Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/b-cell-abnormalities-in-patients-with-chronic-cutaneous-lupus-erythematosus/. Accessed September 18, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-abnormalities-in-patients-with-chronic-cutaneous-lupus-erythematosus/