Reduced CD5+CD24hiCD38hi and interleukin-10+ regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies

Aybar, Lydia T.; McGregor, Julie Anne G.; Hogan, Susan L.; Hu, Yongmei; Mendoza, Carmen; Brant, Elizabeth J.; Poulton, Caroline J.; Henderson, Candace D.; Falk, Ronald J.; Bunch, Donna O.

doi:10.1111/cei.12483

Cited by 52 publications

(43 citation statements)

References 42 publications

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“…In another study, the frequency of Breg cells (numerical but not functional) was significantly reduced even during disease remission. This imbalance may contribute to the high rate of relapse observed in ANCA-related vasculitis [9,10]. Our team purified B cells from human peripheral blood mononuclear cells (PBMCs) of healthy individuals and stained them with fluorescent mAbs to CD25, CD1d, CD86, IL-10, and TGF-β.…”

Section: The Many Faces Of B Regulatory Cells Cd19+cd25highcd1d Highimentioning

confidence: 99%

FoxP3 Expression in Macrophages, Cancer, and B Cells—Is It Real?

Vadasz

Toubi

2016

Clinic Rev Allerg Immunol

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During the last decade, B regulatory cells are appreciated to have a central role in preventing autoimmunity and maintaining self-tolerance. They are characterized by expressing different phenotypic markers and the production of either IL-10 or TGF-β or both. The recent recognition of Fas ligand expressing B regulatory cells as "killer" cells established their role in maintaining viral persistence by preventing effective antiviral immune responses. The forkhead lineage-transcription factor (FoxP3) was considered for many years to be a highly specific intracellular regulatory marker of CD4+CD25+ T regulatory cells. The possibility of FoxP3 being expressed in B regulatory cells was suggested in many studies. Though controversial, FoxP3 expression was also reported in macrophages and cancer cells. Aiming to avoid artifact staining, many researchers required the usage of FoxP3 messenger RNA (mRNA) and PCR in order to prove a true expression of FoxP3 in these different cells. In addition, most studies' report on that FoxP3 expression in all abovementioned cells is related to their status of activation since naïve (non-activated cells) were found poorly FoxP3 expressing. In this review, we present the existing data on FoxP3 expression in non-T-regulatory cells, but we suggest that further studies are needed to better establish this concept.

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Section: The Many Faces Of B Regulatory Cells Cd19+cd25highcd1d Highimentioning

confidence: 99%

FoxP3 Expression in Macrophages, Cancer, and B Cells—Is It Real?

Vadasz

Toubi

2016

Clinic Rev Allerg Immunol

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“…However, when excluding patients in remission with previous rituximab treatment, the differences to HC for the percentages of Breg cells were abolished (data not shown). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. are also in line with some (Lepse et al 2014, Land et al 2015, but not all previous studies (Aybar et al 2015). In the latter study the authors did not observe any differences between patients and HC.…”

Section: Reduced Levels and Altered Phenotypes Of Breg Cells In The Csupporting

confidence: 91%

“…Rituximab treatment has been shown to affect both cell number and the proportions of B cells, with repopulation of CD24 high CD38 high B cells rather than memory (CD27 + ) B cells after treatment (Todd et al 2014, Aybar et al 2015. Thus, when excluding patients in remission previously treated with rituximab in our analysis, MZ-like B cells no longer showed reduced proportions in remission compared with HC.…”

Section: Reduced Levels Of Innate-like B Cells In the Circulation Of mentioning

confidence: 89%

“…Regarding IL-10 positive B cells upon stimulation, Aybar et al showed that the proportion of these cells within the B cell population were reduced during active disease, but that this population rebounded during remission (Aybar et al 2015 (Venhoff et al 2014). …”

Section: Several Studies Have Now Investigated the Frequencies And Fumentioning

confidence: 99%

“…In the latter study the authors did not observe any differences between patients and HC. CD24 high CD38 high B cells have also been investigated by others but the results have been inconclusive (Lepse et al 2014, Todd et al 2014, Aybar et al 2015, Land et al 2015, indicating that this population needs further evaluation. In addition to measurements of the frequencies of the proposed Breg cell populations, we also expanded the investigation of their phenotypes.…”

Section: Reduced Levels and Altered Phenotypes Of Breg Cells In The Cmentioning

confidence: 99%

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The Contribution of Innate Immunity to the Pathogenesis of ANCA-associated Vasculitis

Söderberg¹

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"Nog finns det mål och mening med vår färd -men det är vägen som är mödan värd" − Karin Boye SupervisorMårten Segelmark, Linköping University, Sweden Co-supervisorsPer Eriksson, Linköping University, Sweden Jan Ernerudh, Linköping University, Sweden Tino Kurz, Linköping University, Sweden Faculty opponentPeter Heeringa, University of Groningen, The Netherlands Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitute a group of vasculitides characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of ANCA in the circulation. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. NETs were first described to be involved in capture and elimination of pathogens but dysregulated production and/or clearance of NETs are thought to contribute to vessel inflammation in AAV; directly by damaging endothelial cells and indirectly by acting as a link between the innate and adaptive immune system through the generation of pathogenic PR3-ANCA and MPO-ANCA that can activate neutrophils. ANCA can, however, be found in all individuals and are therefore suggested to belong to the repertoire of natural antibodies produced by innate-like B cells, implying that not all ANCA are pathogenic.In paper I, we found neutrophils in patients to be more prone to undergo NETosis/necrosis spontaneously compared with neutrophils in healthy controls (HC), as well as that active patients possessed elevated levels of NETs in the circulation. Our results also suggest that ANCA during remission could contribute to the clearance of NETs as we observed an inverse relation between ANCA and NETs. In paper II, we observed neutrophils in patients to be more easily activated upon ANCA stimulation as they produced more ROS than neutrophils in HC. In paper III, we showed for the first time that cells of adaptive immunity (B and T cells)

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