Infection with Neoehrlichia mikurensis promotes the development of malignant B-cell lymphomas.
Neoehrlichia mikurensis
immunoglobulin genes
infection
lymphomas
tick-borne disease
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
19
12
2022
received:
12
10
2022
accepted:
04
01
2023
medline:
20
4
2023
pubmed:
18
1
2023
entrez:
17
1
2023
Statut:
ppublish
Résumé
The tick-borne pathogen Neoehrlichia (N.) mikurensis is implicated in persistent infection of the vascular endothelium. B cells are crucial for the host defence to this infection. Chronic stimulation of B cells may result in B-cell transformation and lymphoma. Five patients with malignant B-cell lymphoma and concomitant N. mikurensis infection were investigated regarding clinical picture, lymphoma subtype, B-cell lymphoma immunophenotype and IGHV (variable region of the immunoglobulin heavy) gene repertoire. Three of the five patients improved markedly and ceased lymphoma treatment after doxycycline treatment to eliminate N. mikurensis. Sequencing the B-cell lymphoma IGHV genes revealed preferred usage of the IGHV1 (IGHV1-2, and -69) and IGHV3 (IGHV3-15, -21, -23) families. In conclusion, N. mikurensis infection may drive the development of malignant B-cell lymphomas. Eradication of the pathogen appears to induce remission with apparent curing of the lymphoma in some cases.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
480-488Informations de copyright
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342(8871):575-7.
Ferreri AJ, Ponzoni M, Guidoboni M, De Conciliis C, Resti AG, Mazzi B, et al. Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol. 2005;23(22):5067-73.
Garbe C, Stein H, Dienemann D, Orfanos CE. Borrelia burgdorferi-associated cutaneous B cell lymphoma: clinical and immunohistologic characterization of four cases. J Am Acad Dermatol. 1991;24(4):584-90.
Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F, et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med. 2004;350(3):239-48.
Kuppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3(10):801-12.
Marcucci F, Mele A. Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood. 2011;117(6):1792-8.
Suarez F, Lortholary O, Hermine O, Lecuit M. Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 2006;107(8):3034-44.
Bayerdorffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet. 1995;345(8965):1591-4.
Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med. 1994;330(18):1267-71.
Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V, et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med. 2002;347(2):89-94.
Kelaidi C, Rollot F, Park S, Tulliez M, Christoforov B, Calmus Y, et al. Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas. Leukemia. 2004;18(10):1711-6.
Grankvist A, Andersson PO, Mattsson M, Sender M, Vaht K, Hoper L, et al. Infections with the tick-borne bacterium “Candidatus Neoehrlichia mikurensis” mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases. Clin Infect Dis. 2014;58(12):1716-22.
Maurer F, Keller P, Beuret C, Joha C, Achermann Y, Gubler J, et al. Close geographic association of human neoehrlichiosis and tick populations carrying “Candidatus Neoehrlichia mikurensis” in eastern Switzerland. J Clin Microbiol. 2013;51(1):169-76.
Pekova S, Vydra J, Kabickova H, Frankova S, Haugvicova R, Mazal O, et al. Candidatus Neoehrlichia mikurensis infection identified in 2 hematooncologic patients: benefit of molecular techniques for rare pathogen detection. Diagn Microbiol Infect Dis. 2011;69(3):266-70.
Welinder-Olsson C, Kjellin E, Vaht K, Jacobsson S, Wenneras C. First case of human “Candidatus Neoehrlichia mikurensis” infection in a febrile patient with chronic lymphocytic leukemia. J Clin Microbiol. 2010;48(5):1956-9.
von Loewenich F, Geissdörfer W, Disqué C, Matten J, Schett G, Sakka S, et al. Detection of “Candidatus Neoehrlichia mikurensis” in two patients with severe febrile illnesses: evidence for a European sequence variant. J Clin Microbiol. 2010;48(7):2630-5.
Wass L, Grankvist A, Mattsson M, Gustafsson H, Krogfelt K, Olsen B, et al. Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients. Eur J Clin Microbiol Infect Dis. 2018;37(9):1673-8.
Höper L, Skoog E, Stenson M, Grankvist A, Wass L, Olsen B, et al. Vasculitis due to Candidatus Neoehrlichia mikurensis: a Cohort Study of 40 Swedish patients. Clin Infect Dis. 2021;73(7):e2372-e8.
Wenneras C. Infections with the tick-borne bacterium Candidatus Neoehrlichia mikurensis. Clin Microbiol Infect. 2015;21(7):621-30.
Andreasson K, Jonsson G, Lindell P, Gulfe A, Ingvarsson R, Lindqvist E, et al. Recurrent fever caused by Candidatus Neoehrlichia mikurensis in a rheumatoid arthritis patient treated with rituximab. Rheumatology (Oxford). 2015;54(2):369-71.
Quarsten H, Salte T, Lorentzen AR, Hansen IJW, Hamre R, Forselv KJN, et al. Tick-borne pathogens detected in the blood of immunosuppressed Norwegian patients living in a tick-endemic area. Clin Infect Dis. 2021;73(7):e2364-e71.
Grankvist A, Sandelin LL, Andersson J, Fryland L, Wilhelmsson P, Lindgren PE, et al. Infections with Candidatus Neoehrlichia mikurensis and cytokine responses in 2 persons bitten by Ticks, Sweden. Emerg Infect Dis. 2015;21(8):1462-5.
Welc-Faleciak R, Sinski E, Kowalec M, Zajkowska J, Pancewicz SA. Asymptomatic “Candidatus Neoehrlichia mikurensis” infections in immunocompetent humans. J Clin Microbiol. 2014;52(8):3072-4.
Boyer PH, Baldinger L, Degeilh B, Wirth X, Kamdem CM, Hansmann Y, et al. The emerging tick-borne pathogen Neoehrlichia mikurensis: first French case series and vector epidemiology. Emerg Microbes Infect. 2021;10(1):1731-8.
Markowicz M, Schotta AM, Hoss D, Kundi M, Schray C, Stockinger H, et al. Infections with tickborne pathogens after Tick Bite, Austria, 2015-2018. Emerg Infect Dis. 2021;27(4):1048-56.
van Dongen JJ, Lhermitte L, Bottcher S, Almeida J, van der Velden VH, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26(9):1908-75.
Bushnell B, Rood J, Singer E. BBMerge - accurate paired shotgun read merging via overlap. PLoS One. 2017;12(10):e0185056.
Duez M, Giraud M, Herbert R, Rocher T, Salson M, Thonier F. Vidjil: a web platform for analysis of high-throughput repertoire sequencing. PLoS One. 2016;11(11):e0166126.
Schwameis M, Auer J, Mitteregger D, Simonitsch-Klupp I, Ramharter M, Burgmann H, et al. Anaplasmataceae-specific PCR for diagnosis and therapeutic guidance for symptomatic neoehrlichiosis in immunocompetent host. Emerg Infect Dis. 2016;22(2):281-4.
Kawahara M, Rikihisa Y, Isogai E, Takahashi M, Misumi H, Suto C, et al. Ultrastructure and phylogenetic analysis of ‘Candidatus Neoehrlichia mikurensis’ in the family Anaplasmataceae, isolated from wild rats and found in Ixodes ovatus ticks. Int J Syst Evol Microbiol. 2004;54(5):1837-43.
Wass L, Grankvist A, Bell-Sakyi L, Bergström M, Ulfhammer E, Lingblom C, et al. Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection. Emerg Microb Infect. 2019;8(1):413-25.
Grankvist A, Jaen-Luchoro D, Wass L, Sikora P, Wenneras C. Comparative genomics of clinical isolates of the emerging tick-borne pathogen Neoehrlichia mikurensis. Microorganisms. 2021;9(7):1488.
Dunand CJH, Wilson PC. Restricted, canonical, sterotyped and convergent immunoglobulin responses. Phil Trans R Soc B. 2015;370:20140238.
Chan CH, Hadlock KG, Foung SK, Levy S. V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen. Blood. 2001;97(4):1023-6.
Chen F, Tzarum N, Wilson IA, Law M. VH1-69 antiviral broadly neutralizing antibodies: genetics, structures, and relevance to rational vaccine design. Curr Opin Virol. 2019;34:149-59.
Hatzi K, Catera R, Moreno Atanasio C, Fischetti VA, Allen SL, Kolitz JE, et al. Chronic lymphocytic leukemia immunoglobulins display bacterial reactivity that converges and diverges from auto-/poly-reactivity and IGHV mutation status. Clin Immunol. 2016;172:44-51.
Craig VJ, Arnold I, Gerke C, Huynh MQ, Wundisch T, Neubauer A, et al. Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins. Blood. 2010;115(3):581-91.
Sangesland M, Yousif AS, Ronsard L, Kazer SW, Zhu AL, Gatter GJ, et al. A single human VH-gene allows for a broad-Spectrum antibody response targeting bacterial lipopolysaccharides in the blood. Cell Rep. 2020;32(8):108065.
Bikos V, Darzentas N, Hadzidimitriou A, Davis Z, Hockley S, Traverse-Glehen A, et al. Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications. Leukemia. 2012;26(7):1638-46.
Burger JA. Treatment of chronic lymphocytic leukemia. N Engl J Med. 2020;383(5):460-73.
Sakuma H, Nakamura T, Uemura N, Chiba T, Sugiyama T, Asaka M, et al. Immunoglobulin VH gene analysis in gastric MALT lymphomas. Mod Pathol. 2007;20(4):460-6.
Cohen-Dvashi H, Zehner M, Ehrhardt S, Katz M, Elad N, Klein F, et al. Structural basis for a convergent immune response against Ebola virus. Cell Host Microbe. 2020;27(3):418-427.e4.
Walsh SH, Thorselius M, Johnson A, Soderberg O, Jerkeman M, Bjorck E, et al. Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma. Blood. 2003;101(10):4047-54.