Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients

Teniente-Serra, Aina; Grau-López, Laia; Mansilla, María José; Fernández-Sanmartín, Marco Antonio; Condins, Anna Ester; Ramo-Tello, Cristina; Martı́nez-Cáceres, Eva

doi:10.3109/08916934.2016.1138271

Cited by 24 publications

(30 citation statements)

References 40 publications

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“…A Th1 response has been suggested as important in the pathology of MS, though recent evidence indicates a more complex process than Th1/Th2 polarisation and the involvement of other immune cells, particularly Th17 cells. 16 While an increase in Th1 and Th17 cells has been reported, 24,25 our cohort of MS patients with progressive disease had baseline levels similar to healthy volunteers. Following ASCT, absolute numbers of Th1 and Th2 cells did not change significantly while Th17 cells fell and then returned to normal by six months.…”

Section: Discussionmentioning

confidence: 54%

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

Cull

Hall

Fabis-Pedrini

et al. 2017

Multiple Sclerosis Journal - Experimental, Translational and Cl

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BackgroundAutologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.ObjectiveThe objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.MethodsPatients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.ResultsCD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years.ConclusionThis study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

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Section: Discussionmentioning

confidence: 54%

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

Cull

Hall

Fabis-Pedrini

et al. 2017

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…Conversely, there is disease worsening when BAFF is neutralized with atacicept, which will increase memory B cell numbers (Sergott et al, 2015). Whilst B cell subpopulations fluctuate in MS (Teniente-Serra et al, 2016), it is interesting that people with pediatric MS have generated a substantial pool of memory B cells compared to healthy children and adolescents (Schwarz et al, 2016). Cells within the CD19 +, CD27 + pool may decrease in the blood during relapse and they accumulate within the CNS (Schwarz et al, 2016).…”

Section: Mechanisms Of B Cell Activity In Msmentioning

confidence: 99%

Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis

et al. 2017

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Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19 +, CD27 + memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.

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“…The effect of natalizumab on lymphocyte subpopulations is not fully defined, although it has been described that memory T-cells would be increased in peripheral blood and would induce changes in memory B-cells (90)(91)(92). Moreover, natalizumab treatment interferes with the mechanisms of bone marrow egress of hematopoietic stem cells, inducing an increase of CD34 + cells in peripheral blood, specifically lymphoid progenitors, transitional B-cells, and RTEs (17,91,(93)(94)(95)(96)(97).…”

Section: Natalizumabmentioning

confidence: 99%

“…Moreover, some studies described a decrease of IL-17 production, and Th17 cells, in peripheral blood in MS patients under IFN-β treatment (45,46). It has also been described that the effect of IFN-β causes a decrease of activated and memory T-cells (44,47); on the other hand, it induces an increase of B-cells production-an increase in transitional (immature) Bccells and k-deleting recombination excision circles (KRECs), thereby supporting its use for increasing B-cell release from bone marrow (17,48). Its effect on thymic egress of recent thymic emigrants (RTEs) is still unclear, but it seems that IFN-β may induce a decrease of RTEs and TCR recombination excision circles (TRECs) in peripheral blood (48,49).…”

Section: Interferon a (1a And 1b)mentioning

confidence: 99%

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Immunomonitoring Lymphocyte Subpopulations in Multiple Sclerosis Patients

Teniente‐Serra¹,

Ramo‐Tello

Martı́nez-Cáceres

2017

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

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Abstract:Advances in the understanding of pathogenic mechanisms of diseases have led to the defining of new biomarkers for diagnosis, prognosis, and therapy response. In this context, flow cytometry has been positioned as one of the most useful technologies for monitoring immune-mediated diseases, such as multiple sclerosis (MS), allowing a detailed analysis of lymphocyte subpopulations in peripheral blood. The autoimmune inflammatory response in MS results in changes in lymphocyte subpopulations that might be useful as surrogate markers for the evaluation of disease activity, progression, and monitoring of therapy response. This chapter discusses the role of T-lymphocyte and B-lymphocyte subpopulations in MS pathogenesis, the effect of MS treatments on these subsets, and their potential usefulness as biomarkers of treatment response.

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Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients

Abstract: Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response.

Cited by 24 publications

References 40 publications

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis

Immunomonitoring Lymphocyte Subpopulations in Multiple Sclerosis Patients

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