Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions

B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patie...

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Published inPLoS neglected tropical diseases Vol. 11; no. 12; p. e0006121
Main Authors Negera, Edessa, Walker, Stephen L., Bekele, Yonas, Dockrell, Hazel M., Lockwood, Diana N.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 18.12.2017
Public Library of Science (PLoS)
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Online AccessGet full text
ISSN1935-2735
1935-2727
1935-2735
DOI10.1371/journal.pntd.0006121

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Abstract B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patient group. Therefore, it would be interesting to examine the contribution of B-cells in the pathogenesis of ENL. A case-control study design was used to recruit 30 untreated patients with ENL and 30 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before, during and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of B- cell subsets by flow cytometry. The kinetics of B-cells in patients with ENL before, during and after Prednisolone treatment of ENL was compared with LL patient controls as well as within ENL group. Total B-cells, mature B-cells and resting memory B-cells were not significantly different between patients with ENL reactions and LL controls before treatment. Interestingly, while the percentage of naive B-cells was significantly lower in untreated ENL patients than in LL patient controls, the percentage of activated memory B-cells was significantly higher in these untreated ENL patients than in LL controls. On the other hand, the percentage of tissue-like memory B-cells was considerably low in untreated ENL patients compared to LL controls. It appears that the lower frequency of tissue-like memory B-cells in untreated ENL could promote the B-cell/T-cell interaction in these patients through downregulation of inhibitory molecules unlike in LL patients. Conversely, the increased production of activated memory B-cells in ENL patients could imply the scale up of immune activation through antigen presentation to T-cells. However, the generation and differential function of these memory B-cells need further investigation. The finding of increased percentage of activated memory B-cells in untreated patients with ENL reactions suggests the association of these cells with the ENL pathology. The mechanism by which inflammatory reactions like ENL affecting these memory cells and contributing to the disease pathology is an interesting area to be explored for and could lead to the development of novel and highly efficacious drug for ENL treatment.
AbstractList B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patient group. Therefore, it would be interesting to examine the contribution of B-cells in the pathogenesis of ENL. A case-control study design was used to recruit 30 untreated patients with ENL and 30 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before, during and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of B- cell subsets by flow cytometry. The kinetics of B-cells in patients with ENL before, during and after Prednisolone treatment of ENL was compared with LL patient controls as well as within ENL group. Total B-cells, mature B-cells and resting memory B-cells were not significantly different between patients with ENL reactions and LL controls before treatment. Interestingly, while the percentage of naive B-cells was significantly lower in untreated ENL patients than in LL patient controls, the percentage of activated memory B-cells was significantly higher in these untreated ENL patients than in LL controls. On the other hand, the percentage of tissue-like memory B-cells was considerably low in untreated ENL patients compared to LL controls. It appears that the lower frequency of tissue-like memory B-cells in untreated ENL could promote the B-cell/T-cell interaction in these patients through downregulation of inhibitory molecules unlike in LL patients. Conversely, the increased production of activated memory B-cells in ENL patients could imply the scale up of immune activation through antigen presentation to T-cells. However, the generation and differential function of these memory B-cells need further investigation. The finding of increased percentage of activated memory B-cells in untreated patients with ENL reactions suggests the association of these cells with the ENL pathology. The mechanism by which inflammatory reactions like ENL affecting these memory cells and contributing to the disease pathology is an interesting area to be explored for and could lead to the development of novel and highly efficacious drug for ENL treatment.
B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patient group. Therefore, it would be interesting to examine the contribution of B-cells in the pathogenesis of ENL. A case-control study design was used to recruit 30 untreated patients with ENL and 30 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before, during and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of B- cell subsets by flow cytometry. The kinetics of B-cells in patients with ENL before, during and after Prednisolone treatment of ENL was compared with LL patient controls as well as within ENL group. Total B-cells, mature B-cells and resting memory B-cells were not significantly different between patients with ENL reactions and LL controls before treatment. Interestingly, while the percentage of naive B-cells was significantly lower in untreated ENL patients than in LL patient controls, the percentage of activated memory B-cells was significantly higher in these untreated ENL patients than in LL controls. On the other hand, the percentage of tissue-like memory B-cells was considerably low in untreated ENL patients compared to LL controls. It appears that the lower frequency of tissue-like memory B-cells in untreated ENL could promote the B-cell/T-cell interaction in these patients through downregulation of inhibitory molecules unlike in LL patients. Conversely, the increased production of activated memory B-cells in ENL patients could imply the scale up of immune activation through antigen presentation to T-cells. However, the generation and differential function of these memory B-cells need further investigation. The finding of increased percentage of activated memory B-cells in untreated patients with ENL reactions suggests the association of these cells with the ENL pathology. The mechanism by which inflammatory reactions like ENL affecting these memory cells and contributing to the disease pathology is an interesting area to be explored for and could lead to the development of novel and highly efficacious drug for ENL treatment. Some leprosy patients develop reactions which cause a significant morbidity and mortality in leprosy patients. There are two types of leprosy reactions, type 1 and type 2 reactions. Type 2 or Erythema nodosum leprosum (ENL) is an immune-mediated inflammatory complication of leprosy which occurs in lepromatous and borderline lepromatous leprosy patients. The exact cause of ENL is unknown. Immune-complexes and T-cells are suggested as the aetiology of ENL. However, the contribution of B-cells in ENL reactions has never been addressed. In the present study we described the role of B-cell subsets in ENL reaction and compared with non reactional LL patient controls before, during and after corticosteroids treatment. We found increased antigen experienced and activated B-cells in untreated ENL patients compared to those without the reaction (LL patients). This implies that B-cells are associated with ENL pathology. Therefore, the finding provides a ground for future research targeting B-cells to develop effective drug for ENL treatment.
B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patient group. Therefore, it would be interesting to examine the contribution of B-cells in the pathogenesis of ENL. A case-control study design was used to recruit 30 untreated patients with ENL and 30 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before, during and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of B- cell subsets by flow cytometry. The kinetics of B-cells in patients with ENL before, during and after Prednisolone treatment of ENL was compared with LL patient controls as well as within ENL group. Total B-cells, mature B-cells and resting memory B-cells were not significantly different between patients with ENL reactions and LL controls before treatment. Interestingly, while the percentage of naive B-cells was significantly lower in untreated ENL patients than in LL patient controls, the percentage of activated memory B-cells was significantly higher in these untreated ENL patients than in LL controls. On the other hand, the percentage of tissue-like memory B-cells was considerably low in untreated ENL patients compared to LL controls. It appears that the lower frequency of tissue-like memory B-cells in untreated ENL could promote the B-cell/T-cell interaction in these patients through downregulation of inhibitory molecules unlike in LL patients. Conversely, the increased production of activated memory B-cells in ENL patients could imply the scale up of immune activation through antigen presentation to T-cells. However, the generation and differential function of these memory B-cells need further investigation. The finding of increased percentage of activated memory B-cells in untreated patients with ENL reactions suggests the association of these cells with the ENL pathology. The mechanism by which inflammatory reactions like ENL affecting these memory cells and contributing to the disease pathology is an interesting area to be explored for and could lead to the development of novel and highly efficacious drug for ENL treatment.B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although Erythema Nodosum Leprosum (ENL) is an inflammatory complication of leprosy, the role of B- cell subsets has never been studied in this patient group. Therefore, it would be interesting to examine the contribution of B-cells in the pathogenesis of ENL. A case-control study design was used to recruit 30 untreated patients with ENL and 30 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before, during and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of B- cell subsets by flow cytometry. The kinetics of B-cells in patients with ENL before, during and after Prednisolone treatment of ENL was compared with LL patient controls as well as within ENL group. Total B-cells, mature B-cells and resting memory B-cells were not significantly different between patients with ENL reactions and LL controls before treatment. Interestingly, while the percentage of naive B-cells was significantly lower in untreated ENL patients than in LL patient controls, the percentage of activated memory B-cells was significantly higher in these untreated ENL patients than in LL controls. On the other hand, the percentage of tissue-like memory B-cells was considerably low in untreated ENL patients compared to LL controls. It appears that the lower frequency of tissue-like memory B-cells in untreated ENL could promote the B-cell/T-cell interaction in these patients through downregulation of inhibitory molecules unlike in LL patients. Conversely, the increased production of activated memory B-cells in ENL patients could imply the scale up of immune activation through antigen presentation to T-cells. However, the generation and differential function of these memory B-cells need further investigation. The finding of increased percentage of activated memory B-cells in untreated patients with ENL reactions suggests the association of these cells with the ENL pathology. The mechanism by which inflammatory reactions like ENL affecting these memory cells and contributing to the disease pathology is an interesting area to be explored for and could lead to the development of novel and highly efficacious drug for ENL treatment.
Audience Academic
Author Lockwood, Diana N.
Walker, Stephen L.
Bekele, Yonas
Dockrell, Hazel M.
Negera, Edessa
AuthorAffiliation 2 Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
Institut Pasteur, FRANCE
1 London School of Hygiene and Tropical Medicine (LSHTM), Faculty of Infectious Tropical Diseases, London, United Kingdom
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  surname: Negera
  fullname: Negera, Edessa
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  givenname: Stephen L.
  surname: Walker
  fullname: Walker, Stephen L.
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  givenname: Yonas
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  fullname: Bekele, Yonas
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  givenname: Hazel M.
  surname: Dockrell
  fullname: Dockrell, Hazel M.
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  givenname: Diana N.
  surname: Lockwood
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29253897$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright COPYRIGHT 2017 Public Library of Science
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Negera E, Walker SL, Bekele Y, Dockrell HM, Lockwood DN (2017) Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions. PLoS Negl Trop Dis 11(12): e0006121. https://doi.org/10.1371/journal.pntd.0006121
2017 Negera et al 2017 Negera et al
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Negera E, Walker SL, Bekele Y, Dockrell HM, Lockwood DN (2017) Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions. PLoS Negl Trop Dis 11(12): e0006121. https://doi.org/10.1371/journal.pntd.0006121
Copyright_xml – notice: COPYRIGHT 2017 Public Library of Science
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Negera E, Walker SL, Bekele Y, Dockrell HM, Lockwood DN (2017) Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions. PLoS Negl Trop Dis 11(12): e0006121. https://doi.org/10.1371/journal.pntd.0006121
– notice: 2017 Negera et al 2017 Negera et al
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Negera E, Walker SL, Bekele Y, Dockrell HM, Lockwood DN (2017) Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions. PLoS Negl Trop Dis 11(12): e0006121. https://doi.org/10.1371/journal.pntd.0006121
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Snippet B-cells, in addition to antibody secretion, have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases. Although...
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SubjectTerms Anti-Inflammatory Agents - therapeutic use
Antibodies, Bacterial - immunology
Antigen presentation
Antigens
B cells
B-Lymphocytes - immunology
Biology and Life Sciences
Blood
Care and treatment
Case-Control Studies
Cells
Computer memory
Cytometry
Development and progression
Disease
Drugs
Effector cells
Erythema
Erythema nodosum
Erythema Nodosum - drug therapy
Erythema Nodosum - immunology
Erythema Nodosum - pathology
Erythema nodosum leprosum
Ethiopia
Flow cytometry
Funding
Gangrene
Hepatitis
HIV
Human immunodeficiency virus
Humans
Hygiene
Immune response
Immunologic Memory - immunology
Immunological memory
Immunoregulation
Infections
Inflammatory diseases
Kinetics
Leprosy
Leprosy - immunology
Leprosy - microbiology
Leprosy - pathology
Leukocytes (mononuclear)
Lymphocyte Count
Lymphocytes B
Lymphocytes T
Medicine
Medicine and Health Sciences
Memory cells
Molecules
Mycobacterium leprae - immunology
Pathogenesis
Pathology
Patients
Peripheral blood mononuclear cells
Prednisolone
Prednisolone - therapeutic use
Reaction kinetics
Recruitment
Recruitment (fisheries)
Rheumatoid arthritis
Secretion
T cell receptors
T-Lymphocytes - immunology
Tissue
Tissues
Tropical diseases
Tumor necrosis factor-TNF
Viral infections
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Title Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions
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