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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2023

Open Access 01-12-2023 | Tuberculosis | Research

Memory B-cells are enriched in the blood of patients with acute Buruli ulcer disease: a prospective observational study

Authors: Jonathan Kofi Adjei, Wilfred Aniagyei, Ernest Adankwah, Julia Seyfarth, Ertan Mayatepek, Daniel Antwi Berko, Nancy Ackam, Max Efui Annani-Akollor, Samuel Asamoah Sakyi, Yaw Ampem Amoako, Dorcas Owusu, Marc Jacobsen, Richard Odame Phillips

Published in: BMC Infectious Diseases | Issue 1/2023

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Abstract

Background

Buruli ulcer disease (BUD) caused by Mycobacterium (M.) ulcerans is characterized by necrotic skin lesions. As for other mycobacterial infections, e.g., tuberculosis, the immune response is important for host protection. B-cells may play a role in antimycobacterial immunity but studies characterizing the B-cell repertoire and memory generation in BUD and during the course of treatment are scarce.

Methods

We investigated the adaptive immune cell repertoire in children with BUD and healthy matched controls by flow cytometry. Analyses prior to treatment, also in a study group of patients with tuberculosis, as well as three time points during BUD treatment (i.e., week 8, 16, and 32) were performed. In addition, BUD disease severity as well as treatment response were analysed for association with B-cell repertoire differences.

Results

Children with BUD had comparable total B- and T-cell proportions but differed largely in B-cell subsets. Memory B-cell (B mem) proportions were higher in children with BUD whereas regulatory B-cell (B reg) proportions were lower as compared to healthy controls and tuberculosis patients. Lower naïve (B naïve) and higher transitional B-cell (B trans) proportions characterized children with BUD in comparison with tuberculosis patients. Under treatment, B mem proportions decreased significantly whereas proportions of B reg and B naive increased concomitantly in children with BUD. Also, we found significant correlation between lesion size and B mem as well as B reg. However, we did not detect associations between treatment efficacy and B-cell proportions.

Conclusions

These results suggest a role of B-cell subsets in the immune response against M. ulcerans. Furthermore, changes in B-cell subset proportions may be used as markers for treatment monitoring in BUD.
Appendix
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Literature
1.
Amofah G, Bonsu F, Tetteh C, Okrah J, Asamoa K, Asiedu K, Addy J. Buruli ulcer in Ghana: results of a national case search. Emerg Infect Dis. 2002;8(2):167–70.CrossRefPubMedPubMedCentral
2.
Bretzel G, Beissner M. PCR detection of Mycobacterium ulcerans-significance for clinical practice and epidemiology. Expert Rev Mol Diagn. 2018;18(12):1063–74.CrossRefPubMed
3.
Yotsu RR, Murase C, Sugawara M, Suzuki K, Nakanaga K, Ishii N, Asiedu K. Revisiting Buruli ulcer. J Dermatol. 2015;42(11):1033–41.CrossRefPubMed
4.
sheets WHO-F. : Buruli Ulcer (Mycobacterium Ulcerans Infection). In.: WHO; 2022.
5.
Doig KD, Holt KE, Fyfe JA, Lavender CJ, Eddyani M, Portaels F, Yeboah-Manu D, Pluschke G, Seemann T, Stinear TP. On the origin of Mycobacterium ulcerans, the causative agent of Buruli ulcer. BMC Genomics. 2012;13:258.CrossRefPubMedPubMedCentral
6.
Marion E, Song OR, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V, et al. Mycobacterial toxin induces analgesia in buruli ulcer by targeting the angiotensin pathways. Cell. 2014;157(7):1565–76.CrossRefPubMed
7.
En J, Goto M, Nakanaga K, Higashi M, Ishii N, Saito H, Yonezawa S, Hamada H, Small PL. Mycolactone is responsible for the painlessness of Mycobacterium ulcerans infection (buruli ulcer) in a murine study. Infect Immun. 2008;76(5):2002–7.CrossRefPubMedPubMedCentral
8.
George KM, Pascopella L, Welty DM, Small PL. A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells. Infect Immun. 2000;68(2):877–83.CrossRefPubMedPubMedCentral
9.
Phillips R, Horsfield C, Kuijper S, Sarfo SF, Obeng-Baah J, Etuaful S, Nyamekye B, Awuah P, Nyarko KM, Osei-Sarpong F, et al. Cytokine response to antigen stimulation of whole blood from patients with Mycobacterium ulcerans disease compared to that from patients with tuberculosis. Clin Vaccine Immunol. 2006;13(2):253–7.CrossRefPubMedPubMedCentral
10.
Sarfo FS, Phillips RO, Rangers B, Mahrous EA, Lee RE, Tarelli E, Asiedu KB, Small PL, Wansbrough-Jones MH. Detection of Mycolactone A/B in Mycobacterium ulcerans-infected human tissue. PLoS Negl Trop Dis. 2010;4(1):e577.CrossRefPubMedPubMedCentral
11.
Nausch N, Antwi-Berko D, Mubarik Y, Abass KM, Owusu W, Owusu-Dabo E, Debrah LB, Debrah AY, Jacobsen M, Phillips RO. Analysis of Mycobacterium ulcerans-specific T-cell cytokines for diagnosis of Buruli ulcer disease and as potential indicator for disease progression. PLoS Negl Trop Dis. 2017;11(2):e0005415.CrossRefPubMedPubMedCentral
12.
Converse PJ, Nuermberger EL, Almeida DV, Grosset JH. Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife? Future Microbiol. 2011;6(10):1185–98.CrossRefPubMed
13.
Beissner M, Arens N, Wiedemann F, Piten E, Kobara B, Bauer M, Herbinger KH, Badziklou K, Banla Kere A, Löscher T, et al. Treatment outcome of patients with Buruli Ulcer Disease in Togo. PLoS Negl Trop Dis. 2015;9(10):e0004170.CrossRefPubMedPubMedCentral
14.
Frimpong M, Agbavor B, Duah MS, Loglo A, Sarpong FN, Boakye-Appiah J, Abass KM, Dongyele M, Amofa G, Tuah W, et al. Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: relationship to bacterial load. PLoS Negl Trop Dis. 2019;13(8):e0007689.CrossRefPubMedPubMedCentral
15.
Barogui YT, Klis SA, Johnson RC, Phillips RO, van der Veer E, van Diemen C, van der Werf TS, Stienstra Y. Genetic susceptibility and predictors of paradoxical reactions in Buruli Ulcer. PLoS Negl Trop Dis. 2016;10(4):e0004594.CrossRefPubMedPubMedCentral
16.
Fraga AG, Cruz A, Martins TG, Torrado E, Saraiva M, Pereira DR, Meyers WM, Portaels F, Silva MT, Castro AG, et al. Mycobacterium ulcerans triggers T-cell immunity followed by local and regional but not systemic immunosuppression. Infect Immun. 2011;79(1):421–30.CrossRefPubMed
17.
Schipper HS, Rutgers B, Huitema MG, Etuaful SN, Westenbrink BD, Limburg PC, Timens W, van der Werf TS. Systemic and local interferon-gamma production following Mycobacterium ulcerans infection. Clin Exp Immunol. 2007;150(3):451–9.CrossRefPubMedPubMedCentral
18.
Gooding TM, Johnson PD, Smith M, Kemp AS, Robins-Browne RM. Cytokine profiles of patients infected with Mycobacterium ulcerans and unaffected household contacts. Infect Immun. 2002;70(10):5562–7.CrossRefPubMedPubMedCentral
19.
Coutanceau E, Decalf J, Martino A, Babon A, Winter N, Cole ST, Albert ML, Demangel C. Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med. 2007;204(6):1395–403.CrossRefPubMedPubMedCentral
20.
Ruf MT, Bolz M, Vogel M, Bayi PF, Bratschi MW, Sopho GE, Yeboah-Manu D, Um Boock A, Junghanss T, Pluschke G. Spatial distribution of Mycobacterium ulcerans in Buruli Ulcer Lesions: implications for Laboratory diagnosis. PLoS Negl Trop Dis. 2016;10(6):e0004767.CrossRefPubMedPubMedCentral
21.
Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet. 2006;367(9525):1849–58.CrossRefPubMed
22.
Debacker M, Aguiar J, Steunou C, Zinsou C, Meyers WM, Guedenon A, Scott JT, Dramaix M, Portaels F. Mycobacterium ulcerans disease (Buruli ulcer) in rural hospital, Southern Benin, 1997–2001. Emerg Infect Dis. 2004;10(8):1391–8.CrossRefPubMedPubMedCentral
23.
Vincent QB, Ardant MF, Adeye A, Goundote A, Saint-André JP, Cottin J, Kempf M, Agossadou D, Johnson C, Abel L, et al. Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study. Lancet Glob Health. 2014;2(7):e422–430.CrossRefPubMed
24.
Phillips RO, Sarfo FS, Osei-Sarpong F, Boateng A, Tetteh I, Lartey A, Adentwe E, Opare W, Asiedu KB, Wansbrough-Jones M. Sensitivity of PCR targeting Mycobacterium ulcerans by use of fine-needle aspirates for diagnosis of Buruli ulcer. J Clin Microbiol. 2009;47(4):924–6.CrossRefPubMedPubMedCentral
25.
Organization WH. Role of specific antibiotics in Mycobacterium Ulcerans (Buruli Ulcer) Management. In.; 2016.
26.
Bourguignon P, Clement F, Renaud F, Le Bras V, Koutsoukos M, Burny W, Moris P, Lorin C, Collard A, Leroux-Roels G, et al. Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naive HIV-1-infected patients. J Immunol Methods. 2014;414:1–10.CrossRefPubMed
27.
Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Bello I, Cilio CM, Wong FS, Schloot NC, T-Cell Workshop Committee IoDS. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society. Clin Exp Immunol. 2011;163(1):33–49.CrossRefPubMedPubMedCentral
28.
Aniagyei W, Adjei JK, Adankwah E, Seyfarth J, Mayatepek E, Berko DA, Sakyi SA, Debrah LB, Debrah AY, Hoerauf A et al. Doxycycline treatment of Mansonella perstans infected individuals affects immune cell activation and causes long-term T-cell polarization. Clin Infect Dis 2022.
29.
Sebina I, Biraro IA, Dockrell HM, Elliott AM, Cose S. Circulating B-lymphocytes as potential biomarkers of tuberculosis infection activity. PLoS ONE. 2014;9(9):e106796.CrossRefPubMedPubMedCentral
30.
Shimizu T, Nagafuchi Y, Harada H, Tsuchida Y, Tsuchiya H, Hanata N, Tateishi S, Kanda H, Sumitomo S, Shoda H, et al. Decreased peripheral blood memory B cells are associated with the presence of interstitial lung disease in rheumatoid arthritis: a case-control study. Mod Rheumatol. 2021;31(1):127–32.CrossRefPubMed
31.
Phillips R, Sarfo FS, Guenin-Macé L, Decalf J, Wansbrough-Jones M, Albert ML, Demangel C. Immunosuppressive signature of cutaneous Mycobacterium ulcerans infection in the peripheral blood of patients with buruli ulcer disease. J Infect Dis. 2009;200(11):1675–84.CrossRefPubMed
32.
Niang F, Sarfo FS, Frimpong M, Guenin-Macé L, Wansbrough-Jones M, Stinear T, Phillips RO, Demangel C. Metabolomic profiles delineate mycolactone signature in Buruli ulcer disease. Sci Rep. 2015;5:17693.CrossRefPubMedPubMedCentral
33.
Sarfo FS, Le Chevalier F, Aka N, Phillips RO, Amoako Y, Boneca IG, Lenormand P, Dosso M, Wansbrough-Jones M, Veyron-Churlet R, et al. Mycolactone diffuses into the peripheral blood of Buruli ulcer patients–implications for diagnosis and disease monitoring. PLoS Negl Trop Dis. 2011;5(7):e1237.CrossRefPubMedPubMedCentral
34.
Sarfo FS, Phillips R, Asiedu K, Ampadu E, Bobi N, Adentwe E, Lartey A, Tetteh I, Wansbrough-Jones M. Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2010;54(9):3678–85.CrossRefPubMedPubMedCentral
35.
Ugai K, Koffi DY, Kouadio K, Yao A, Yotsu RR. Nutritional status and wound healing in patients with Mycobacterium ulcerans disease (Buruli ulcer): a pilot study from rural Cote d’Ivoire. Eur J Dermatol. 2022;32(2):227–36.PubMed
36.
World Medical A. World medical association declaration of helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4.CrossRef
Metadata
Title
Memory B-cells are enriched in the blood of patients with acute Buruli ulcer disease: a prospective observational study
Authors
Jonathan Kofi Adjei
Wilfred Aniagyei
Ernest Adankwah
Julia Seyfarth
Ertan Mayatepek
Daniel Antwi Berko
Nancy Ackam
Max Efui Annani-Akollor
Samuel Asamoah Sakyi
Yaw Ampem Amoako
Dorcas Owusu
Marc Jacobsen
Richard Odame Phillips
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2023
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-023-08370-1

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