Article
Looking for a SLE signature on peripheral B cell subsets: does a preponderant CD38 positive plasmablast-subpopulation lack CD73 as a sign of a diminished B regulatory pool?
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Authors
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Magdalena Siekierka-Harreis
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Rheumatologie, Düsseldorf
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Madita Schroedter
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität, Rheumatologie, Düsseldorf
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Gamal Chehab
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
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Jutta Richter
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
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Stefan Vordenbäumen
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
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Matthias Schneider
- Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
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Georg Pongratz
- Universitätsklinik Düsseldorf, Poliklinik, Funktionsbereich und Hiller Forschungszentrum Rheumatologie, Düsseldorf
| Published: | September 4, 2017 |
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Outline
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Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by polyclonal Bcell activation, production of dsDNA-autoantibodies and cytokines. Subsets of Bcells play a central role in SLE-pathogenesis. The inflammatory milieu is characterized by the accumulation of adenosine, which confers immunosuppressive effects. In SLE, the role of CD73, an enzyme involved in the extracellular generation of adenosine from ATP, is not well characterized. This study aimed to characterize expression of CD73 Bcell subsets of SLE-patients as compared to healthy controls (HC).
Methods: Bcell subsets were characterized from peripheral blood of 23 SLE patients attending the outpatient clinic at the Rheumatology Unit of University Hospital Düsseldorf and of 15 HC by FACS. All patients fulfilled the revised SLE-criteria of ACR and were randomly collected in clinical remission state (SLEDAI 1.1±1.9).
Results: By comparison of Bcell subsets between SLE and HC, CD38 was dominantly expressed by SLE-patients (SLE 74.2%±12.9% vs. HC 64.2%±12.2%; p(MWU)=0.018). Furthermore, SLE-patients showed an increase in CD19+IgD-CD27+CD38high plasmablasts (SLE 2.1%±3.4% vs HC 0,4%±0.4%, p(MWU)<0.001). Moreover, SLE-plasmablasts showed decreased CD73 expression as compared to HC (SLE 2.1%±1.9% vs HC 3.5%±2.2%; p(MWU)=0.034). SLE-Bcells revealed a trend towards an augmented CD38highCD138+plasmacell-fraction (SLE 0.40%±0.5% vs HC 0.08%±0.07%; p=0.07), without any difference in CD73 expression. On the other hand, exhausted-memory B cell fraction (CD19+IgD-CD27-CD21-CD138-), showed an increased CD73 expression in SLE (SLE 13.7%±9.2% vs HC 6.2%±5.4%; p=0.004).
Conclusion: Our study confirms CD38+ plasmablasts as being increased in peripheral blood from SLE patients as compared to HC. Furthermore, the data reveal a deficiency for CD73 on SLE plasmablasts, which suggests a decreased regulatory capacity of SLE plasmablasts as compared to HC, supporting the notion of a reduced regulatory B cell pool in SLE. On the other hand, the enlarged CD73+ exhausted-memory pool in SLE could point to an accelerated flow of CD73+ regulatory B cells into an exhausted B cell fraction. These findings support the hypothesis of a persistent regulatory B cell defect even in a state of SLE remission.
