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dc.contributor.author
Landegren, Nils  
dc.contributor.author
Sharon, Donald  
dc.contributor.author
Shum, Anthony K.  
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Khan, Imran S.  
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Fasano, Kayla J.  
dc.contributor.author
Hallgren, Åsa  
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Kampf, Caroline  
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Freyhult, Eva  
dc.contributor.author
Ardesjö Lundgren, Brita  
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Alimohammadi, Mohammad  
dc.contributor.author
Rathsman, Sandra  
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Ludvigsson, Jonas F.  
dc.contributor.author
Lundh, Dan  
dc.contributor.author
Motrich, Ruben Dario  
dc.contributor.author
Rivero, Virginia Elena  
dc.contributor.author
Fong, Lawrence  
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Giwercman, Aleksander  
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Gustafsson, Jan  
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Perheentupa, Jaakko  
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Husebye, Eystein S.  
dc.contributor.author
Anderson, Mark S.  
dc.contributor.author
Snyder, Michael  
dc.contributor.author
Kämpe, Olle  
dc.date.available
2023-01-26T13:07:57Z  
dc.date.issued
2015-06-17  
dc.identifier.citation
Landegren, Nils; Sharon, Donald; Shum, Anthony K.; Khan, Imran S.; Fasano, Kayla J.; et al.; Transglutaminase 4 as a prostate autoantigen in male subfertility; American Association for the Advancement of Science; Science Translational Medicine; 7; 292; 17-6-2015; 1-11  
dc.identifier.issn
1946-6242  
dc.identifier.uri
http://hdl.handle.net/11336/185736  
dc.description.abstract
Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
American Association for the Advancement of Science  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Prostatitis  
dc.subject
Autoimmunity  
dc.subject
Male infertility  
dc.subject
APS1  
dc.subject.classification
Inmunología  
dc.subject.classification
Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Transglutaminase 4 as a prostate autoantigen in male subfertility  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2023-01-23T16:39:14Z  
dc.identifier.eissn
1946-6234  
dc.journal.volume
7  
dc.journal.number
292  
dc.journal.pagination
1-11  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Washington  
dc.description.fil
Fil: Landegren, Nils. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Sharon, Donald. University of Stanford; Estados Unidos. University of Yale; Estados Unidos  
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Fil: Shum, Anthony K.. University of California; Estados Unidos  
dc.description.fil
Fil: Khan, Imran S.. University of California; Estados Unidos  
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Fil: Fasano, Kayla J.. University of California; Estados Unidos  
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Fil: Hallgren, Åsa. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Kampf, Caroline. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Freyhult, Eva. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Ardesjö Lundgren, Brita. Swedish University of Agricultural Sciences; Suecia  
dc.description.fil
Fil: Alimohammadi, Mohammad. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Rathsman, Sandra. Örebro University Hospital; Suecia  
dc.description.fil
Fil: Ludvigsson, Jonas F.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia  
dc.description.fil
Fil: Lundh, Dan. University of Skövde; Suecia  
dc.description.fil
Fil: Motrich, Ruben Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina  
dc.description.fil
Fil: Fong, Lawrence. University of California; Estados Unidos  
dc.description.fil
Fil: Giwercman, Aleksander. Lund University; Suecia  
dc.description.fil
Fil: Gustafsson, Jan. Uppsala Universitet; Suecia  
dc.description.fil
Fil: Perheentupa, Jaakko. University of Helsinki; Finlandia  
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Fil: Husebye, Eystein S.. University of Bergen; Noruega  
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Fil: Anderson, Mark S.. University of California; Estados Unidos  
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Fil: Snyder, Michael. University of Stanford; Estados Unidos  
dc.description.fil
Fil: Kämpe, Olle. Karolinska Huddinge Hospital; Suecia. Uppsala Universitet; Suecia  
dc.journal.title
Science Translational Medicine  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/scitranslmed.aaa9186  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1126/scitranslmed.aaa9186