{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:14:16Z","timestamp":1783721656000,"version":"3.55.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005760","name":"University of Gothenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Microbiol Immunol"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tick-borne\n                    <jats:italic>Neoehrlichia mikurensis<\/jats:italic>\n                    is the cause of neoehrlichiosis, an infectious disease that features fever and vascular events. Compromised B-cell immunity is a risk factor for severe neoehrlichiosis, indicating the importance of antibodies in host defense. The development of serological assays has been hampered by the difficulty of culturing these intracellular bacteria. Here we present the first serological test for\n                    <jats:italic>N. mikurensis<\/jats:italic>\n                    , an ELISA for human IgM and IgG antibody responses to a P44\/Msp2 protein of\n                    <jats:italic>N. mikurensis.<\/jats:italic>\n                    Serum or plasma from immunocompetent (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200944) and immunosuppressed (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200960) Swedish adults infected with\n                    <jats:italic>N. mikurensis<\/jats:italic>\n                    , with and without symptoms, were analyzed and compared with blood samples from non-infected immunocompetent individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917). Sera from non-infected children (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200923) and plasma from cord blood (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) were also analyzed. Immunocompetent neoehrlichiosis adults had higher IgM and IgG antibody levels compared with immunosuppressed neoehrlichiosis patients treated with the B-cell suppressive agent rituximab. There were no significant differences in the IgM or IgG antibody levels between immunocompetent individuals with symptomatic versus asymptomatic\n                    <jats:italic>N. mikurensis<\/jats:italic>\n                    infection. Sera from healthy children contained high levels of IgM antibodies, despite no evidence of current infection with\n                    <jats:italic>N. mikurensis<\/jats:italic>\n                    nor previous exposure to tick bites as reflected by negative\n                    <jats:italic>Borrelia<\/jats:italic>\n                    serology. This IgM response was absent in cord blood plasma (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910), indicating it was not due to natural IgM antibodies. The high constitutional IgM antibody levels to\n                    <jats:italic>N. mikurensis<\/jats:italic>\n                    in children may explain why there have been no reports of pediatric neoehrlichiosis.\n                  <\/jats:p>","DOI":"10.1007\/s00430-026-00869-z","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:23:18Z","timestamp":1773314598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Detection of human antibody responses to tick-borne Neoehrlichia mikurensis"],"prefix":"10.1007","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8580-3593","authenticated-orcid":false,"given":"Rima","family":"Alsalihi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaitz","family":"Aranburu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lingblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Wass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Lewerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Edvinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"M\u00e5rtensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Skoog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Carin","family":"Lundell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Bergstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Grankvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wenner\u00e5s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"869_CR1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.3201\/eid1607.091907","volume":"16","author":"JS Fehr","year":"2010","unstructured":"Fehr JS, Bloemberg GV, Ritter C, Hombach M, Luscher TF, Weber R, Keller PM (2010) Septicemia caused by tick-borne bacterial pathogen Candidatus Neoehrlichia mikurensis. Emerg Infect Dis 16:1127\u20131129. https:\/\/doi.org\/10.3201\/eid1607.091907","journal-title":"Emerg Infect Dis"},{"key":"869_CR2","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1128\/jcm.02423-09","volume":"48","author":"C Welinder-Olsson","year":"2010","unstructured":"Welinder-Olsson C, Kjellin E, Vaht K, Jacobsson S, Wenner\u00e5S C (2010) First case of human \u201cCandidatus Neoehrlichia mikurensis\u201d infection in a febrile patient with chronic lymphocytic leukemia. J Clin Microbiol 48:1956\u20131959. https:\/\/doi.org\/10.1128\/jcm.02423-09","journal-title":"J Clin Microbiol"},{"key":"869_CR3","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1128\/jcm.00588-10","volume":"48","author":"FD Von Loewenich","year":"2010","unstructured":"Von Loewenich FD, Gei\u00dfd\u00f6Rfer W, Disqu\u00e9 C, Matten J, Schett G, Sakka SG, Bogdan C (2010) Detection of \u201cCandidatus Neoehrlichia mikurensis\u201d in two patients with severe febrile illnesses: evidence for a European sequence variant. J Clin Microbiol 48:2630\u20132635. https:\/\/doi.org\/10.1128\/jcm.00588-10","journal-title":"J Clin Microbiol"},{"key":"869_CR4","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1093\/cid\/ciu189","volume":"58","author":"A Grankvist","year":"2014","unstructured":"Grankvist A, Andersson PO, Mattsson M, Sender M, Vaht K, Hoper L, Sakiniene E, Trysberg E, Stenson M, Fehr J, Pekova S, Bogdan C, Bloemberg G, Wenneras C (2014) Infections with the tick-borne bacterium \u201cCandidatus Neoehrlichia mikurensis\u201d mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases. Clin Infect Dis 58:1716\u20131722. https:\/\/doi.org\/10.1093\/cid\/ciu189","journal-title":"Clin Infect Dis"},{"key":"869_CR5","doi-asserted-by":"publisher","first-page":"e2372","DOI":"10.1093\/cid\/ciaa1217","volume":"73","author":"L H\u00f6per","year":"2021","unstructured":"H\u00f6per L, Skoog E, Stenson M, Grankvist A, Wass L, Olsen B, Nilsson K, M\u00e5rtensson A, S\u00f6derlind J, Sakinis A, Wenner\u00e5s C (2021) Vasculitis due to Candidatus Neoehrlichia mikurensis: a cohort study of 40 Swedish patients. Clin Infect Dis 73:e2372\u2013e2378. https:\/\/doi.org\/10.1093\/cid\/ciaa1217","journal-title":"Clin Infect Dis"},{"key":"869_CR6","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1080\/22221751.2019.1584017","volume":"8","author":"L Wass","year":"2019","unstructured":"Wass L, Grankvist A, Bell-Sakyi L, Bergstr\u00f6m M, Ulfhammer E, Lingblom C, Wenner\u00e5s C (2019) Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection. Emerg Microbes Infect 8:413\u2013425. https:\/\/doi.org\/10.1080\/22221751.2019.1584017","journal-title":"Emerg Microbes Infect"},{"key":"869_CR7","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1007\/s10096-024-04909-5","volume":"43","author":"C Wenner\u00e5s","year":"2024","unstructured":"Wenner\u00e5s C, Wass L, Bergstr\u00f6m B, Grankvist A, Lingblom C (2024) Ten years of detecting Neoehrlichia mikurensis infections in Sweden: demographic, clinical and inflammatory parameters. Eur J Clin Microbiol Infect Dis 43:2083\u20132092. https:\/\/doi.org\/10.1007\/s10096-024-04909-5","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"869_CR8","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1080\/22221751.2021.1973347","volume":"10","author":"PH Boyer","year":"2021","unstructured":"Boyer PH, Baldinger L, Degeilh B, Wirth X, Kamdem CM, Hansmann Y, Zilliox L, Boulanger N, Jaulhac B (2021) The emerging tick-borne pathogen Neoehrlichia mikurensis: first French case series and vector epidemiology. Emerg Microbes Infect 10:1731\u20131738. https:\/\/doi.org\/10.1080\/22221751.2021.1973347","journal-title":"Emerg Microbes Infect"},{"key":"869_CR9","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.3201\/eid2108.150060","volume":"21","author":"A Grankvist","year":"2015","unstructured":"Grankvist A, Sandelin LL, Andersson J, Fryland L, Wilhelmsson P, Lindgren P-E, Forsberg P, Wenner\u00e5s C (2015) Infections with Candidatus Neoehrlichia mikurensis and cytokine responses in 2 persons bitten by ticks, Sweden. Emerg Infect Dis 21:1462\u20131465. https:\/\/doi.org\/10.3201\/eid2108.150060","journal-title":"Emerg Infect Dis"},{"key":"869_CR10","doi-asserted-by":"publisher","DOI":"10.1080\/23744235.2022.2087732","author":"L Labb\u00e9 Sandelin","year":"2022","unstructured":"Labb\u00e9 Sandelin L, Olofsson J, Tolf C, Rohl\u00e9n L, Brudin L, Tjernberg I, Lindgren P-E, Olsen B, Waldenstr\u00f6m J (2022) Detection of Neoehrlichia mikurensis DNA in blood donors in southeastern Sweden. Infect Dis Lond. https:\/\/doi.org\/10.1080\/23744235.2022.2087732","journal-title":"Infect Dis Lond"},{"key":"869_CR11","doi-asserted-by":"publisher","DOI":"10.3201\/eid2704.203366","author":"M Markowicz","year":"2021","unstructured":"Markowicz M, Sch\u00f6tta A-M, H\u00f6ss D, Kundi M, Schray C, Stockinger H, Stanek G (2021) Infections with tickborne pathogens after tick bite, Austria, 2015\u20132018. Emerg Infect Dis. https:\/\/doi.org\/10.3201\/eid2704.203366","journal-title":"Emerg Infect Dis"},{"key":"869_CR12","doi-asserted-by":"publisher","first-page":"3072","DOI":"10.1128\/jcm.00741-14","volume":"52","author":"R Welc-Fal\u0119ciak","year":"2014","unstructured":"Welc-Fal\u0119ciak R, Si\u0144ski E, Kowalec M, Zajkowska J, Pancewicz SA (2014) Asymptomatic \u201cCandidatus Neoehrlichia mikurensis\u201d infections in immunocompetent humans. J Clin Microbiol 52:3072\u20133074. https:\/\/doi.org\/10.1128\/jcm.00741-14","journal-title":"J Clin Microbiol"},{"key":"869_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2024.102391","volume":"16","author":"AO Dahlberg","year":"2025","unstructured":"Dahlberg AO, Aase A, Reiso H, Midgard R, Quarsten H (2025) Detection of Neoehrlichia mikurensis in 11 persons who attribute their persistent health complaints to a tick-borne disease. Ticks Tick-borne Dis 16:102391. https:\/\/doi.org\/10.1016\/j.ttbdis.2024.102391","journal-title":"Ticks Tick-borne Dis"},{"key":"869_CR14","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/zph.13073","volume":"70","author":"A Goren","year":"2023","unstructured":"Goren A, Mysterud A, Jore S, Viljugrein H, Bakka H, Vindenes Y (2023) Demographic patterns in Lyme borreliosis seasonality over 25 years. Zoonoses Public Health 70:647\u2013655. https:\/\/doi.org\/10.1111\/zph.13073","journal-title":"Zoonoses Public Health"},{"key":"869_CR15","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.cmi.2015.02.030","volume":"21","author":"C Wenner\u00e5s","year":"2015","unstructured":"Wenner\u00e5s C (2015) Infections with the tick-borne bacterium Candidatus Neoehrlichia mikurensis. Clin Microbiol Infect 21:621\u2013630. https:\/\/doi.org\/10.1016\/j.cmi.2015.02.030","journal-title":"Clin Microbiol Infect"},{"key":"869_CR16","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.3390\/microorganisms9071488","volume":"9","author":"A Grankvist","year":"2021","unstructured":"Grankvist A, Ja\u00e9n-Luchoro D, Wass L, Sikora P, Wenner\u00e5s C (2021) Comparative genomics of clinical isolates of the emerging tick-borne pathogen Neoehrlichia mikurensis. Microorganisms 9:1488. https:\/\/doi.org\/10.3390\/microorganisms9071488","journal-title":"Microorganisms"},{"key":"869_CR17","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1128\/jcm.35.10.2606-2611.1997","volume":"35","author":"N Zhi","year":"1997","unstructured":"Zhi N, Rikihisa Y, Kim HY, Wormser GP, Horowitz HW (1997) Comparison of major antigenic proteins of six strains of the human granulocytic ehrlichiosis agent by Western immunoblot analysis. J Clin Microbiol 35:2606\u20132611. https:\/\/doi.org\/10.1128\/jcm.35.10.2606-2611.1997","journal-title":"J Clin Microbiol"},{"key":"869_CR18","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1128\/JCM.00880-15","volume":"53","author":"A Grankvist","year":"2015","unstructured":"Grankvist A, Moore ER, Svensson Stadler L, Pekova S, Bogdan C, Geissdorfer W, Grip-Linden J, Brandstrom K, Marsal J, Andreasson K, Lewerin C, Welinder-Olsson C, Wenneras C (2015) Multilocus sequence analysis of clinical \u201cCandidatus Neoehrlichia mikurensis\u201d strains from Europe. J Clin Microbiol 53:3126\u20133132. https:\/\/doi.org\/10.1128\/JCM.00880-15","journal-title":"J Clin Microbiol"},{"key":"869_CR19","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1007\/s10096-018-3298-3","volume":"37","author":"L Wass","year":"2018","unstructured":"Wass L, Grankvist A, Mattsson M, Gustafsson H, Krogfelt K, Olsen B, Nilsson K, Martensson A, Quarsten H, Henningsson AJ, Wenneras C (2018) Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients. Eur J Clin Microbiol Infect Dis 37:1673\u20131678. https:\/\/doi.org\/10.1007\/s10096-018-3298-3","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"869_CR20","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1111\/bjh.18652","volume":"201","author":"C Wenneras","year":"2023","unstructured":"Wenneras C, Aranburu A, Wass L, Grankvist A, Staffas A, Soboli A, Martensson IL, Fogelstrand L, Lewerin C (2023) Infection with Neoehrlichia mikurensis promotes the development of malignant B-cell lymphomas. Br J Haematol 201:480\u2013488. https:\/\/doi.org\/10.1111\/bjh.18652","journal-title":"Br J Haematol"},{"key":"869_CR21","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.molimm.2012.03.030","volume":"51","author":"GN Sivalingam","year":"2012","unstructured":"Sivalingam GN, Shepherd AJ (2012) An analysis of B-cell epitope discontinuity. Mol Immunol 51:304\u2013309. https:\/\/doi.org\/10.1016\/j.molimm.2012.03.030","journal-title":"Mol Immunol"},{"key":"869_CR22","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.ttbdis.2017.05.004","volume":"8","author":"H Quarsten","year":"2017","unstructured":"Quarsten H, Grankvist A, H\u00f8yvoll L, Myre IB, Skarpaas T, Kjelland V, Wenneras C, Noraas S (2017) CandidatusNeoehrlichia mikurensis and Borrelia burgdorferi sensu lato detected in the blood of Norwegian patients with erythema migrans. Ticks Tick-borne Dis 8:715\u2013720. https:\/\/doi.org\/10.1016\/j.ttbdis.2017.05.004","journal-title":"Ticks Tick-borne Dis"},{"key":"869_CR23","doi-asserted-by":"publisher","first-page":"e2364","DOI":"10.1093\/cid\/ciaa971","volume":"73","author":"H Quarsten","year":"2021","unstructured":"Quarsten H, Salte T, Lorentzen \u00c5R, Hansen IJW, Hamre R, Forselv KJN, \u00d8ines \u00d8, Wenner\u00e5s C, Noraas S (2021) Tick-borne pathogens detected in the blood of immunosuppressed Norwegian patients living in a tick-endemic area. Clin Infect Dis 73:e2364\u2013e2371. https:\/\/doi.org\/10.1093\/cid\/ciaa971","journal-title":"Clin Infect Dis"},{"key":"869_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102466","volume":"19","author":"K Kridin","year":"2020","unstructured":"Kridin K, Ahmed AR (2020) Post-rituximab immunoglobulin M (IgM) hypogammaglobulinemia. Autoimmun Rev 19:102466. https:\/\/doi.org\/10.1016\/j.autrev.2020.102466","journal-title":"Autoimmun Rev"},{"key":"869_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00066","author":"C Gr\u00f6nwall","year":"2012","unstructured":"Gr\u00f6nwall C, Vas J, Silverman GJ (2012) Protective roles of natural IgM antibodies. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2012.00066","journal-title":"Front Immunol"},{"key":"869_CR26","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1080\/23744235.2017.1347815","volume":"49","author":"C Wenner\u00e5s","year":"2017","unstructured":"Wenner\u00e5s C, Goldblatt D, Zancolli M, Mattsson M, Wass L, H\u00f6rkk\u00f6 S, Ros\u00e9n A (2017) Natural IgM antibodies in the immune defence against neoehrlichiosis. Infect Dis 49:809\u2013816. https:\/\/doi.org\/10.1080\/23744235.2017.1347815","journal-title":"Infect Dis"},{"key":"869_CR27","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.4049\/jimmunol.1200878","volume":"189","author":"DD Jones","year":"2012","unstructured":"Jones DD, DeIulio GA, Winslow GM (2012) Antigen-driven induction of polyreactive IgM during intracellular bacterial infection. J Immunol 189:1440\u20131447. https:\/\/doi.org\/10.4049\/jimmunol.1200878","journal-title":"J Immunol"}],"container-title":["Medical Microbiology and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-026-00869-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00430-026-00869-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-026-00869-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:23:19Z","timestamp":1773314599000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00430-026-00869-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["869"],"URL":"https:\/\/doi.org\/10.1007\/s00430-026-00869-z","relation":{},"ISSN":["0300-8584","1432-1831"],"issn-type":[{"value":"0300-8584","type":"print"},{"value":"1432-1831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"assertion":[{"value":"15 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None of the authors declare conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"9"}}