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This is true for the widespread protozoan<jats:italic>Toxoplasma gondii<\/jats:italic>which establishes long-lasting parasitism in metazoans, humans included. This microbe successively unfolds distinct genetic programs that direct the transition from high to low replicative potential inside host cells. As a slow-replicating cell, the<jats:italic>T. gondii<\/jats:italic>bradyzoite developmental stage persists enclosed in a cyst compartment within tissues including the nervous system, being held by a sustained immune equilibrium which accounts for the prolonged clinically silent phase of parasitism. Serological surveys indicate that nearly one third of the human population has been exposed to<jats:italic>T. gondii<\/jats:italic>and possibly host bradyzoites. Because any disruption of the immune balance drives the reverse transition from bradyzoite to fast replicating tachyzoite and uncontrolled growth of the latter, these people are at risk for life-threatening disease. While serological tests for discriminating recent from past infection are available, there is yet no immunogenic biomarker used in the serological test to allow ascertaining the presence of persistent bradyzoites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Capitalizing on genetically engineered parasites induced to produce mature bradyzoites in vitro, we have identified the BCLA\/MAG2 protein being restricted to the bradyzoite and the cyst envelope. Using laboratory mice as relevant<jats:italic>T. gondii<\/jats:italic>host models, we demonstrated that BCLA\/MAG2 drives the generation of antibodies that recognize bradyzoite and the enveloping cyst structure. We have designed an ELISA assay based on a bacterially produced BCLA recombinant polypeptide, which was validated using a large collection of sera from mice of different genetic backgrounds and infected with bcla+ or bcla-null cystogenic and non-cystogenic<jats:italic>T. gondii<\/jats:italic>strains. To refine the design of the ELISA assay, we applied high-resolution BCLA epitope mapping and identified a specific combination of peptides and accordingly set up a selective and sensitive ELISA assay which allowed the detection of anti-BCLA\/MAG2 antibodies in the sera of human patients with various forms of toxoplasmosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We brought proof of principle that anti-BCLA\/MAG2 antibodies serve as specific and sensitive serological markers in the perspective of a combinatorial strategy for detection of persistent<jats:italic>T. gondii<\/jats:italic>parasitism.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12915-021-00959-9","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:57:42Z","timestamp":1612832262000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection"],"prefix":"10.1186","volume":"19","author":[{"given":"C\u00e9line","family":"Dard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Swale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Brenier-Pinchart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayana C.","family":"Farhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Bellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Gladys","family":"Robert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Cannella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Pelloux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Tardieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-8233","authenticated-orcid":false,"given":"Mohamed-Ali","family":"Hakimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"issue":"8","key":"959_CR1","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.ijpara.2009.02.004","volume":"39","author":"LM Weiss","year":"2009","unstructured":"Weiss LM, Dubey Jitender P. 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Accessed 01 Sept 2020."}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-021-00959-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12915-021-00959-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-021-00959-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T18:41:16Z","timestamp":1671129676000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbiol.biomedcentral.com\/articles\/10.1186\/s12915-021-00959-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,9]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["959"],"URL":"https:\/\/doi.org\/10.1186\/s12915-021-00959-9","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,9]]},"assertion":[{"value":"30 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Human sera were retrospectively selected from the biobank collection of the Parasitology-Mycology Clinical Laboratory in Grenoble Alpes University Hospital in France. This biobank is registered with the French Ministry of Health under the number DC-2008-582. The Quality Management System is applied in the Parasitology-Mycology Clinical Laboratory in the University Grenoble Alpes Hospital and our laboratory is accredited according to ISO 15189 standard. All the sera were collected in agreement with the institution and after no patient\u2019s opposition.Mouse care and experimental procedures were performed under pathogen-free conditions in accordance with established institutional guidance and approved protocols from the Institutional Animal Care and Use Committee of the University Grenoble Alpes (agreement n\u00b0B3851610006).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"M.-A.H., C. D., C. S., and M.-P. B.-P. are co-inventors on a patent application related to this work that covers the use of BCLA as a biomarker for diagnosis of chronic toxoplasmosis in humans. Inserm and its valorization subsidiary Inserm-Transfert are involved in the pending patent application. The other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}