Search

Your search keyword '"Bosticardo, Marita"' showing total 345 results
Start Over Author "Bosticardo, Marita"
345 results on '"Bosticardo, Marita"'

1. A spatial human thymus cell atlas mapped to a continuous tissue axis

Author

Yayon, Nadav, Kedlian, Veronika R., Boehme, Lena, Suo, Chenqu, Wachter, Brianna T., Beuschel, Rebecca T., Amsalem, Oren, Polanski, Krzysztof, Koplev, Simon, Tuck, Elizabeth, Dann, Emma, Van Hulle, Jolien, Perera, Shani, Putteman, Tom, Predeus, Alexander V., Dabrowska, Monika, Richardson, Laura, Tudor, Catherine, Kreins, Alexandra Y., Engelbert, Justin, Stephenson, Emily, Kleshchevnikov, Vitalii, De Rita, Fabrizio, Crossland, David, Bosticardo, Marita, Pala, Francesca, Prigmore, Elena, Chipampe, Nana-Jane, Prete, Martin, Fei, Lijiang, To, Ken, Barker, Roger A., He, Xiaoling, Van Nieuwerburgh, Filip, Bayraktar, Omer Ali, Patel, Minal, Davies, E Graham, Haniffa, Muzlifah A., Uhlmann, Virginie, Notarangelo, Luigi D., Germain, Ronald N., Radtke, Andrea J., Marioni, John C., Taghon, Tom, and Teichmann, Sarah A.

Published
2024
Full Text
View/download PDF

3. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Author

Yu, David, Miller, Corey, Feng, Yi, Guichard, Audrey, Béziat, Vivien, Bustamante, Jacinta, Pan-Hammarström, Qiang, Zhang, Yu, Rosen, Lindsey, Holland, Steve, Bosticardo, Marita, Kenney, Heather, Castagnoli, Riccardo, Slade, Charlotte, Boztuğ, Kaan, Mahlaoui, Nizar, Latour, Sylvain, Abraham, Roshini, Lougaris, Vassilios, Hauck, Fabian, Sediva, Anna, Atschekzei, Faranaz, Sogkas, Georgios, Poli, M, Slatter, Mary, Palterer, Boaz, Keller, Michael, Pinzon-Charry, Alberto, Sullivan, Anna, Droney, Luke, Suan, Daniel, Wong, Melanie, Kane, Alisa, Hu, Hannah, Ma, Cindy, Grombiříková, Hana, Ciznar, Peter, Dalal, Ilan, Aladjidi, Nathalie, Hie, Miguel, Lazaro, Estibaliz, Franco, Jose, Keles, Sevgi, Malphettes, Marion, Pasquet, Marlene, Maccari, Maria, Meinhardt, Andrea, Ikinciogullari, Aydan, Shahrooei, Mohammad, Celmeli, Fatih, Frosk, Patrick, Goodnow, Christopher, Gray, Paul, Belot, Alexandre, Kuehn, Hye, Rosenzweig, Sergio, Miyara, Makoto, Licciardi, Francesco, Servettaz, Amélie, Barlogis, Vincent, Le Guenno, Guillaume, Herrmann, Vera-Maria, Kuijpers, Taco, Ducoux, Grégoire, Sarrot-Reynauld, Françoise, Schuetz, Catharina, Cunningham-Rundles, Charlotte, Rieux-Laucat, Frédéric, Tangye, Stuart, Sobacchi, Cristina, Doffinger, Rainer, Warnatz, Klaus, Grimbacher, Bodo, Fieschi, Claire, Berteloot, Laureline, Bryant, Vanessa, Trouillet Assant, Sophie, Su, Helen, Neven, Benedicte, Abel, Laurent, Zhang, Qian, Boisson, Bertrand, Cobat, Aurélie, Jouanguy, Emmanuelle, Kampe, Olle, Bastard, Paul, Roifman, Chaim, Landegren, Nils, Notarangelo, Luigi, Le Voyer, Tom, Parent, Audrey, Liu, Xian, Cederholm, Axel, Gervais, Adrian, Rosain, Jérémie, Nguyen, Tina, Perez Lorenzo, Malena, Rackaityte, Elze, Rinchai, Darawan, and Zhang, Peng

Subjects
Humans, Autoantibodies, COVID-19, Gain of Function Mutation, Genetic Predisposition to Disease, Heterozygote, I-kappa B Proteins, Interferon Type I, Loss of Function Mutation, NF-kappa B, NF-kappa B p52 Subunit, Pneumonia, Viral, Thymus Gland, Thyroid Epithelial Cells
Abstract

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

Published
2023

4. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Author

Le Voyer, Tom, Parent, Audrey V., Liu, Xian, Cederholm, Axel, Gervais, Adrian, Rosain, Jérémie, Nguyen, Tina, Perez Lorenzo, Malena, Rackaityte, Elze, Rinchai, Darawan, Zhang, Peng, Bizien, Lucy, Hancioglu, Gonca, Ghillani-Dalbin, Pascale, Charuel, Jean-Luc, Philippot, Quentin, Gueye, Mame Sokhna, Maglorius Renkilaraj, Majistor Raj Luxman, Ogishi, Masato, Soudée, Camille, Migaud, Mélanie, Rozenberg, Flore, Momenilandi, Mana, Riller, Quentin, Imberti, Luisa, Delmonte, Ottavia M., Müller, Gabriele, Keller, Baerbel, Orrego, Julio, Franco Gallego, William Alexander, Rubin, Tamar, Emiroglu, Melike, Parvaneh, Nima, Eriksson, Daniel, Aranda-Guillen, Maribel, Berrios, David I., Vong, Linda, Katelaris, Constance H., Mustillo, Peter, Raedler, Johannes, Bohlen, Jonathan, Bengi Celik, Jale, Astudillo, Camila, Winter, Sarah, McLean, Catriona, Guffroy, Aurélien, DeRisi, Joseph L., Yu, David, Miller, Corey, Feng, Yi, Guichard, Audrey, Béziat, Vivien, Bustamante, Jacinta, Pan-Hammarström, Qiang, Zhang, Yu, Rosen, Lindsey B., Holland, Steve M., Bosticardo, Marita, Kenney, Heather, Castagnoli, Riccardo, Slade, Charlotte A., Boztuğ, Kaan, Mahlaoui, Nizar, Latour, Sylvain, Abraham, Roshini S., Lougaris, Vassilios, Hauck, Fabian, Sediva, Anna, Atschekzei, Faranaz, Sogkas, Georgios, Poli, M. Cecilia, Slatter, Mary A., Palterer, Boaz, Keller, Michael D., Pinzon-Charry, Alberto, Sullivan, Anna, Droney, Luke, Suan, Daniel, Wong, Melanie, Kane, Alisa, Hu, Hannah, Ma, Cindy, Grombiříková, Hana, Ciznar, Peter, Dalal, Ilan, Aladjidi, Nathalie, Hie, Miguel, Lazaro, Estibaliz, Franco, Jose, Keles, Sevgi, Malphettes, Marion, Pasquet, Marlene, Maccari, Maria Elena, Meinhardt, Andrea, Ikinciogullari, Aydan, Shahrooei, Mohammad, Celmeli, Fatih, Frosk, Patrick, Goodnow, Christopher C., Gray, Paul E., Belot, Alexandre, Kuehn, Hye Sun, Rosenzweig, Sergio D., Miyara, Makoto, Licciardi, Francesco, Servettaz, Amélie, Barlogis, Vincent, Le Guenno, Guillaume, Herrmann, Vera-Maria, Kuijpers, Taco, Ducoux, Grégoire, Sarrot-Reynauld, Françoise, Schuetz, Catharina, Cunningham-Rundles, Charlotte, Rieux-Laucat, Frédéric, Tangye, Stuart G., Sobacchi, Cristina, Doffinger, Rainer, Warnatz, Klaus, Grimbacher, Bodo, Fieschi, Claire, Berteloot, Laureline, Bryant, Vanessa L., Trouillet Assant, Sophie, Su, Helen, Neven, Benedicte, Abel, Laurent, Zhang, Qian, Boisson, Bertrand, Cobat, Aurélie, Jouanguy, Emmanuelle, Kampe, Olle, Bastard, Paul, Roifman, Chaim M., Landegren, Nils, Notarangelo, Luigi D., Anderson, Mark S., Casanova, Jean-Laurent, and Puel, Anne

Published
2023
Full Text
View/download PDF

5. Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals

Author

Delmonte, Ottavia M., Oguz, Cihan, Dobbs, Kerry, Myint-Hpu, Katherine, Palterer, Boaz, Abers, Michael S., Draper, Deborah, Truong, Meng, Kaplan, Ian M., Gittelman, Rachel M., Zhang, Yu, Rosen, Lindsey B., Snow, Andrew L., Dalgard, Clifton L., Burbelo, Peter D., Imberti, Luisa, Sottini, Alessandra, Quiros-Roldan, Eugenia, Castelli, Francesco, Rossi, Camillo, Brugnoni, Duilio, Biondi, Andrea, Bettini, Laura Rachele, D’Angio, Mariella, Bonfanti, Paolo, Anderson, Megan V., Saracino, Annalisa, Chironna, Maria, Di Stefano, Mariantonietta, Fiore, Jose Ramon, Santantonio, Teresa, Castagnoli, Riccardo, Marseglia, Gian Luigi, Magliocco, Mary, Bosticardo, Marita, Pala, Francesca, Shaw, Elana, Matthews, Helen, Weber, Sarah E., Xirasagar, Sandhya, Barnett, Jason, Oler, Andrew J., Dimitrova, Dimana, Bergerson, Jenna R.E., McDermott, David H., Rao, V. Koneti, Murphy, Philip M., Holland, Steven M., Lisco, Andrea, Su, Helen C., Lionakis, Michail S., Cohen, Jeffrey I., Freeman, Alexandra F., Snyder, Thomas M., Lack, Justin, and Notarangelo, Luigi D.

Published
2024
Full Text
View/download PDF

6. Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency

Author

Pavel-Dinu, Mara, Gardner, Cameron L., Nakauchi, Yusuke, Kawai, Tomoki, Delmonte, Ottavia M., Palterer, Boaz, Bosticardo, Marita, Pala, Francesca, Viel, Sebastien, Malech, Harry L., Ghanim, Hana Y., Bode, Nicole M., Kurgan, Gavin L., Detweiler, Angela M., Vakulskas, Christopher A., Neff, Norma F., Sheikali, Adam, Menezes, Sherah T., Chrobok, Jade, Hernández González, Elaine M., Majeti, Ravindra, Notarangelo, Luigi D., and Porteus, Matthew H.

Published
2024
Full Text
View/download PDF

8. Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling

Author

Nunes-Santos, Cristiane J., Kuehn, HyeSun, Boast, Brigette, Hwang, SuJin, Kuhns, Douglas B., Stoddard, Jennifer, Niemela, Julie E., Fink, Danielle L., Pittaluga, Stefania, Abu-Asab, Mones, Davies, John S., Barr, Valarie A., Kawai, Tomoki, Delmonte, Ottavia M., Bosticardo, Marita, Garofalo, Mary, Carneiro-Sampaio, Magda, Somech, Raz, Gharagozlou, Mohammad, Parvaneh, Nima, Samelson, Lawrence E., Fleisher, Thomas A., Puel, Anne, Notarangelo, Luigi D., Boisson, Bertrand, Casanova, Jean-Laurent, Derfalvi, Beata, and Rosenzweig, Sergio D.

Published
2023
Full Text
View/download PDF

9. Expanded microbiome niches of RAG-deficient patients

Author

Thomas, Jim, Mullikin, James, Young, Alice, Bouffard, Gerry, Barnabas, Betty, Brooks, Shelise, Buchter, Chloe, Crawford, Juyun, Han, Joel, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Marfani, Holly, Montemayor, Casandra, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Black, Sean, Dekhtyar, Mila, Masiello, Cathy, McDowell, Jenny, Park, Morgan, Thomas, Pam, Vemulapalli, Meg, Blaustein, Ryan A., Shen, Zeyang, Kashaf, Sara Saheb, Lee-Lin, ShihQueen, Conlan, Sean, Bosticardo, Marita, Delmonte, Ottavia M., Holmes, Cassandra J., Taylor, Monica E., Banania, Glenna, Nagao, Keisuke, Dimitrova, Dimana, Kanakry, Jennifer A., Su, Helen, Holland, Steven M., Bergerson, Jenna R.E., Freeman, Alexandra F., Notarangelo, Luigi D., Kong, Heidi H., and Segre, Julia A.

Published
2023
Full Text
View/download PDF

10. Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Author

Yakici, Nalan, Kreins, Alexandra Y., Catak, Mehmet Cihangir, Babayeva, Royala, Erman, Baran, Kenney, Heather, Gungor, Hatice Eke, Cea, Pablo A., Kawai, Tomoki, Bosticardo, Marita, Delmonte, Ottavia Maria, Adams, Stuart, Fan, Yu-Tong, Pala, Francesca, Turkyilmaz, Ayberk, Howley, Evey, Worth, Austen, Kot, Hakan, Sefer, Asena Pinar, Kara, Altan, Bulutoglu, Alper, Bilgic-Eltan, Sevgi, Altunbas, Melek Yorgun, Bayram Catak, Feyza, Karakus, Ibrahim Serhat, Karatay, Emrah, Tekeoglu, Sidem Didar, Eser, Metin, Albayrak, Davut, Citli, Senol, Kiykim, Ayca, Karakoc-Aydiner, Elif, Ozen, Ahmet, Ghosh, Sujal, Gohlke, Holger, Orhan, Fazil, Notarangelo, Luigi D., Davies, E. Graham, and Baris, Safa

Published
2023
Full Text
View/download PDF

11. Artificial thymic organoids represent a reliable tool to study T-cell differentiation in patients with severe T-cell lymphopenia

Author

Bosticardo, Marita, Pala, Francesca, Calzoni, Enrica, Delmonte, Ottavia M, Dobbs, Kerry, Gardner, Cameron L, Sacchetti, Nicolo’, Kawai, Tomoki, Garabedian, Elizabeth K, Draper, Debbie, Bergerson, Jenna RE, DeRavin, Suk See, Freeman, Alexandra F, Güngör, Tayfun, Hartog, Nicholas, Holland, Steven M, Kohn, Donald B, Malech, Harry L, Markert, Mary Louise, Weinacht, Katja G, Villa, Anna, Seet, Christopher S, Montel-Hagen, Amelie, Crooks, Gay M, and Notarangelo, Luigi D

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Stem Cell Research - Nonembryonic - Human, Pediatric, Clinical Research, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Antigens, CD34, Cell Differentiation, Hematopoietic Stem Cells, Humans, Lymphopenia, Organoids, Cardiovascular medicine and haematology
Abstract

The study of early T-cell development in humans is challenging because of limited availability of thymic samples and the limitations of in vitro T-cell differentiation assays. We used an artificial thymic organoid (ATO) platform generated by aggregating a DLL4-expressing stromal cell line (MS5-hDLL4) with CD34+ cells isolated from bone marrow or mobilized peripheral blood to study T-cell development from CD34+ cells of patients carrying hematopoietic intrinsic or thymic defects that cause T-cell lymphopenia. We found that AK2 deficiency is associated with decreased cell viability and an early block in T-cell development. We observed a similar defect in a patient carrying a null IL2RG mutation. In contrast, CD34+ cells from a patient carrying a missense IL2RG mutation reached full T-cell maturation, although cell numbers were significantly lower than in controls. CD34+ cells from patients carrying RAG mutations were able to differentiate to CD4+CD8+ cells, but not to CD3+TCRαβ+ cells. Finally, normal T-cell differentiation was observed in a patient with complete DiGeorge syndrome, consistent with the extra-hematopoietic nature of the defect. The ATO system may help determine whether T-cell deficiency reflects hematopoietic or thymic intrinsic abnormalities and define the exact stage at which T-cell differentiation is blocked.

Published
2020

12. Separating the Wheat From the Chaff in Asthma and Bronchiectasis: The Saga Trajectory of a Patient With Adult-Onset RAG1 Deficiency

Author

Chitty Lopez, Maria, Yilmaz, Melis, Diaz-Cabrera, Natalie M., Saco, Tara, Ishmael, Leah, Sotoudeh, Shannon, Bindernagel, Constance, Ujhazi, Boglarka, Gordon, Sumai, Potts, David Evan, Danziger, Roger, Bosticardo, Marita, Kenney, Heather, Illes, Peter, Lee, Sena, Harris, Megan, Cuellar-Rodriguez, Jennifer, Patel, Kapil N., Csomos, Krisztian, Dimitrova, Dimana, Kanakry, Jennifer A., Notarangelo, Luigi D., and Walter, Jolan E.

Published
2023
Full Text
View/download PDF

13. Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis

Author

Bosticardo, Marita, Yamazaki, Yasuhiro, Cowan, Jennifer, Giardino, Giuliana, Corsino, Cristina, Scalia, Giulia, Prencipe, Rosaria, Ruffner, Melanie, Hill, David A, Sakovich, Inga, Yemialyanava, Irma, Tam, Jonathan S, Padem, Nurcicek, Elder, Melissa E, Sleasman, John W, Perez, Elena, Niebur, Hana, Seroogy, Christine M, Sharapova, Svetlana, Gebbia, Jennifer, Kleiner, Gary Ira, Peake, Jane, Abbott, Jordan K, Gelfand, Erwin W, Crestani, Elena, Biggs, Catherine, Butte, Manish J, Hartog, Nicholas, Hayward, Anthony, Chen, Karin, Heimall, Jennifer, Seeborg, Filiz, Bartnikas, Lisa M, Cooper, Megan A, Pignata, Claudio, Bhandoola, Avinash, and Notarangelo, Luigi D

Subjects
Biomedical and Clinical Sciences, Immunology, Rare Diseases, Biotechnology, Genetics, Prevention, Vaccine Related, Biodefense, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Animals, Child, Preschool, Female, Forkhead Transcription Factors, Heterozygote, Humans, Infant, Infant, Newborn, Lymphopenia, Male, Mice, Mice, SCID, Middle Aged, T-Lymphocytes, Thymus Gland, Young Adult, FOXN1, SCID, T cell receptor excision circles, T lymphocytes, newborn screening, thymopoiesis, thymus, Biological Sciences, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4+ but lower than normal CD8+ cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulated that these effects would be more prominent early in life. To test this hypothesis, we analyzed TEC subset frequency and phenotype, early thymic progenitor (ETP) cell count, and expression of FOXN1 target genes (Ccl25, Cxcl12, Dll4, Scf, Psmb11, Prss16, and Cd83) in Foxn1nu/+ (nu/+) mice and age-matched wild-type (+/+) littermate controls. Both the frequency and the absolute count of ETP were significantly reduced in nu/+ mice up to 3 weeks of age. Analysis of the TEC compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. These observations establish a FOXN1 gene dosage effect on thymic function and identify FOXN1 haploinsufficiency as an important genetic determinant of T cell lymphopenia at birth.

Published
2019

14. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

Author

Sacco, Keith, Castagnoli, Riccardo, Vakkilainen, Svetlana, Liu, Can, Delmonte, Ottavia M., Oguz, Cihan, Kaplan, Ian M., Alehashemi, Sara, Burbelo, Peter D., Bhuyan, Farzana, de Jesus, Adriana A., Dobbs, Kerry, Rosen, Lindsey B., Cheng, Aristine, Shaw, Elana, Vakkilainen, Mikko S., Pala, Francesca, Lack, Justin, Zhang, Yu, Fink, Danielle L., Oikonomou, Vasileios, Snow, Andrew L., Dalgard, Clifton L., Chen, Jinguo, Sellers, Brian A., Montealegre Sanchez, Gina A., Barron, Karyl, Rey-Jurado, Emma, Vial, Cecilia, Poli, Maria Cecilia, Licari, Amelia, Montagna, Daniela, Marseglia, Gian Luigi, Licciardi, Francesco, Ramenghi, Ugo, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Eisenstein, Eli M., Imberti, Luisa, Sottini, Alessandra, Biondi, Andrea, Mató, Sayonara, Gerstbacher, Dana, Truong, Meng, Stack, Michael A., Magliocco, Mary, Bosticardo, Marita, Kawai, Tomoki, Danielson, Jeffrey J., Hulett, Tyler, Askenazi, Manor, Hu, Shaohui, Cohen, Jeffrey I., Su, Helen C., Kuhns, Douglas B., Lionakis, Michail S., Snyder, Thomas M., Holland, Steven M., Goldbach-Mansky, Raphaela, Tsang, John S., and Notarangelo, Luigi D.

Published
2022
Full Text
View/download PDF

15. Case report: Artificial thymic organoids facilitate clinical decisions for a patient with a TP63 variant and severe persistent T cell lymphopenia.

Author

Gall, Alevtina, Bosticardo, Marita, Ma, Stacey, Chen, Karin, Amini, Kayla, Pala, Francesca, Delmonte, Ottavia M., Wenger, Tara, Bamshad, Michael, Sleasman, John, Blessing, Matthew, van Oers, Nicolai S. C., Notarangelo, Luigi D., and de la Morena, M. Teresa

Subjects
TRANSCRIPTION factors, T cell differentiation, T cell receptors, T cells, KILLER cells, LYMPHOPENIA
Abstract

Pathogenic variants in the transcription factor TP63 are associated with clinically overlapping syndromes including ectrodactyly-ectodermal dysplasia clefting (EEC) and ankyloblepharon-ectodermal defects-cleft lip/palate (AEC). T cell lymphopenia has rarely been described in individuals with TP63 variants and the cause of the T cell defect is unclear. Here, we present a case of a female infant born with TP63-related syndrome and profound T cell lymphopenia, first uncovered through newborn screening. Flow cytometry analysis revealed low CD4+ naïve T cells and nearly absent CD8+ T cells with intact B and NK cell compartments. A de novo heterozygous pathogenic variant c.1040 G>A (C347Y) in exon 8 of TP63 was identified. An artificial thymic organoid system, to assess the intrinsic ability of the patient's hematopoietic cells to develop into T cells, was performed twice using separate peripheral blood samples. Ex vivo T cell differentiation was evident with the artificial organoid system, suggesting that a thymic stromal cell defect may be the cause of the T cell lymphopenia. Consistent with this, interrogation of publicly available data indicated that TP63 expression in the human thymus is restricted to thymic epithelial cells. Based on these data, congenital athymia was suspected and the patient received an allogenic cultured thymus tissue implant (CTTI). This is the first report of suspected congenital athymia and attempted treatment with CTTI associated with TP63 variant. At 9 months post-implant, peripheral lymphocyte analysis revealed measurable T cell receptor excision circles and presence of CD4+ recent thymic emigrants suggestive of early thymopoiesis. She will continue regular monitoring to ensure restoration of T cell immunity. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

16. Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation

Author

Sereni, Lucia, Castiello, Maria Carmina, Marangoni, Francesco, Anselmo, Achille, di Silvestre, Dario, Motta, Sara, Draghici, Elena, Mantero, Stefano, Thrasher, Adrian J, Giliani, Silvia, Aiuti, Alessandro, Mauri, Pierluigi, Notarangelo, Luigi D, Bosticardo, Marita, and Villa, Anna

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adolescent, Adult, Animals, Autoimmunity, Blood Platelets, CD40 Ligand, Child, Child, Preschool, Female, Humans, Infant, Inflammation, Mice, Inbred C57BL, Mice, Knockout, Platelet Count, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein, Young Adult, Wiskott-Aldrich syndrome, platelet deficiency, CD40 ligand, autoantibodies, autoimmunity, Allergy
Abstract

BACKGROUND:Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive. OBJECTIVE:To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS. METHODS:Phenotypic and functional characterization of megakaryocytes and platelets in mutant CoWas mice and patients with WAS with and without autoantibodies was performed. Platelet antigen expression was examined through a protein expression profile and cluster proteomic interaction network. Platelet immunogenicity was tested by using ELISAs and B-cell and platelet cocultures. RESULTS:CoWas mice showed increased megakaryocyte numbers and normal thrombopoiesis in vitro, but WASp-deficient platelets had short lifespan and high expression of activation markers. Proteomic analysis identified signatures compatible with defects in cytoskeletal reorganization and metabolism yet surprisingly increased antigen-processing capabilities. In addition, WASp-deficient platelets expressed high levels of surface and soluble CD40 ligand and were capable of inducing B-cell activation in vitro. WASp-deficient platelets were highly immunostimulatory in mice and triggered the generation of antibodies specific for WASp-deficient platelets, even in the context of a normal immune system. Patients with WAS also showed platelet hyperactivation and increased plasma soluble CD40 ligand levels correlating with the presence of autoantibodies. CONCLUSION:Overall, these findings suggest that intrinsic defects in WASp-deficient platelets decrease their lifespan and dysregulate immune responses, corroborating the role of platelets as modulators of inflammation and immunity.

Published
2018

18. Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity

Author

Delmonte, Ottavia M., Bergerson, Jenna R.E., Burbelo, Peter D., Durkee-Shock, Jessica R., Dobbs, Kerry, Bosticardo, Marita, Keller, Michael D., McDermott, David H., Rao, V. Koneti, Dimitrova, Dimana, Quiros-Roldan, Eugenia, Imberti, Luisa, Ferrè, Elise M.N., Schmitt, Monica, Lafeer, Christine, Pfister, Justina, Shaw, Dawn, Draper, Deborah, Truong, Meng, Ulrick, Jean, DiMaggio, Tom, Urban, Amanda, Holland, Steven M., Lionakis, Michail S., Cohen, Jeffrey I., Ricotta, Emily E., Notarangelo, Luigi D., and Freeman, Alexandra F.

Published
2021
Full Text
View/download PDF

19. EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay

Author

Volpi, Stefano, Yamazaki, Yasuhiro, Brauer, Patrick M, van Rooijen, Ellen, Hayashida, Atsuko, Slavotinek, Anne, Kuehn, Hye Sun, Di Rocco, Maja, Rivolta, Carlo, Bortolomai, Ileana, Du, Likun, Felgentreff, Kerstin, de Bruin, Lisa Ott, Hayashida, Kazutaka, Freedman, George, Marcovecchio, Genni Enza, Capuder, Kelly, Rath, Prisni, Luche, Nicole, Hagedorn, Elliott J, Buoncompagni, Antonella, Royer-Bertrand, Beryl, Giliani, Silvia, Poliani, Pietro Luigi, Imberti, Luisa, Dobbs, Kerry, Poulain, Fabienne E, Martini, Alberto, Manis, John, Linhardt, Robert J, Bosticardo, Marita, Rosenzweig, Sergio Damian, Lee, Hane, Puck, Jennifer M, Zúñiga-Pflücker, Juan Carlos, Zon, Leonard, Park, Pyong Woo, Superti-Furga, Andrea, and Notarangelo, Luigi D

Subjects
Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Nonembryonic - Non-Human, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research, Pediatric, Rare Diseases, Congenital Structural Anomalies, 2.1 Biological and endogenous factors, Aetiology, Animals, Bone Diseases, Developmental, Child, Preschool, Developmental Disabilities, Female, Heparitin Sulfate, Humans, Immunologic Deficiency Syndromes, Induced Pluripotent Stem Cells, Infant, Lymphocytes, Mutation, N-Acetylglucosaminyltransferases, Zebrafish, Medical and Health Sciences, Immunology
Abstract

We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. Patient-derived fibroblasts showed abnormal HS composition and altered fibroblast growth factor 2 signaling, which was rescued by overexpression of wild-type EXTL3 cDNA. Interleukin-2-mediated STAT5 phosphorylation in patients' lymphocytes was markedly reduced. Interbreeding of the extl3-mutant zebrafish (box) with Tg(rag2:green fluorescent protein) transgenic zebrafish revealed defective thymopoiesis, which was rescued by injection of wild-type human EXTL3 RNA. Targeted differentiation of patient-derived induced pluripotent stem cells showed a reduced expansion of lymphohematopoietic progenitor cells and defects of thymic epithelial progenitor cell differentiation. These data identify EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development.

Published
2017

21. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency

Author

Castiello, M, Brandas, C, Ferrari, S, Porcellini, S, Sacchetti, N, Canarutto, D, Draghici, E, Merelli, I, Barcella, M, Pelosi, G, Vavassori, V, Varesi, A, Jacob, A, Scala, S, Basso Ricci, L, Paulis, M, Strina, D, Di Verniere, M, Sergi Sergi, L, Serafini, M, Holland, S, Bergerson, J, De Ravin, S, Malech, H, Pala, F, Bosticardo, M, Brombin, C, Cugnata, F, Calzoni, E, Crooks, G, Notarangelo, L, Genovese, P, Naldini, L, Villa, A, Castiello, Maria Carmina, Brandas, Chiara, Ferrari, Samuele, Porcellini, Simona, Sacchetti, Nicolò, Canarutto, Daniele, Draghici, Elena, Merelli, Ivan, Barcella, Matteo, Pelosi, Gabriele, Vavassori, Valentina, Varesi, Angelica, Jacob, Aurelien, Scala, Serena, Basso Ricci, Luca, Paulis, Marianna, Strina, Dario, Di Verniere, Martina, Sergi Sergi, Lucia, Serafini, Marta, Holland, Steven M., Bergerson, Jenna R. E., De Ravin, Suk See, Malech, Harry L., Pala, Francesca, Bosticardo, Marita, Brombin, Chiara, Cugnata, Federica, Calzoni, Enrica, Crooks, Gay M., Notarangelo, Luigi D., Genovese, Pietro, Naldini, Luigi, Villa, Anna, Castiello, M, Brandas, C, Ferrari, S, Porcellini, S, Sacchetti, N, Canarutto, D, Draghici, E, Merelli, I, Barcella, M, Pelosi, G, Vavassori, V, Varesi, A, Jacob, A, Scala, S, Basso Ricci, L, Paulis, M, Strina, D, Di Verniere, M, Sergi Sergi, L, Serafini, M, Holland, S, Bergerson, J, De Ravin, S, Malech, H, Pala, F, Bosticardo, M, Brombin, C, Cugnata, F, Calzoni, E, Crooks, G, Notarangelo, L, Genovese, P, Naldini, L, Villa, A, Castiello, Maria Carmina, Brandas, Chiara, Ferrari, Samuele, Porcellini, Simona, Sacchetti, Nicolò, Canarutto, Daniele, Draghici, Elena, Merelli, Ivan, Barcella, Matteo, Pelosi, Gabriele, Vavassori, Valentina, Varesi, Angelica, Jacob, Aurelien, Scala, Serena, Basso Ricci, Luca, Paulis, Marianna, Strina, Dario, Di Verniere, Martina, Sergi Sergi, Lucia, Serafini, Marta, Holland, Steven M., Bergerson, Jenna R. E., De Ravin, Suk See, Malech, Harry L., Pala, Francesca, Bosticardo, Marita, Brombin, Chiara, Cugnata, Federica, Calzoni, Enrica, Crooks, Gay M., Notarangelo, Luigi D., Genovese, Pietro, Naldini, Luigi, and Villa, Anna

Abstract

Recombination activating genes (RAGs) are tightly regulated during lymphoid differentiation, and their mutations cause a spectrum of severe immunological disorders. Hematopoietic stem and progenitor cell (HSPC) transplantation is the treatment of choice but is limited by donor availability and toxicity. To overcome these issues, we developed gene editing strategies targeting a corrective sequence into the human RAG1 gene by homology-directed repair (HDR) and validated them by tailored two-dimensional, three-dimensional, and in vivo xenotransplant platforms to assess rescue of expression and function. Whereas integration into intron 1 of RAG1 achieved suboptimal correction, in-frame insertion into exon 2 drove physiologic human RAG1 expression and activity, allowing disruption of the dominant-negative effects of unrepaired hypomorphic alleles. Enhanced HDR-mediated gene editing enabled the correction of human RAG1 in HSPCs from patients with hypomorphic RAG1 mutations to overcome T and B cell differentiation blocks. Gene correction efficiency exceeded the minimal proportion of functional HSPCs required to rescue immunodeficiency in Rag1(-/- )mice, supporting the clinical translation of HSPC gene editing for the treatment of RAG1 deficiency.

Published
2024

22. The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants

Author

Materna, Marie, primary, Delmonte, Ottavia M., additional, Bosticardo, Marita, additional, Momenilandi, Mana, additional, Conrey, Peyton E., additional, Charmeteau-De Muylder, Bénédicte, additional, Bravetti, Clotilde, additional, Bellworthy, Rebecca, additional, Cederholm, Axel, additional, Staels, Frederik, additional, Ganoza, Christian A., additional, Darko, Samuel, additional, Sayed, Samir, additional, Le Floc’h, Corentin, additional, Ogishi, Masato, additional, Rinchai, Darawan, additional, Guenoun, Andrea, additional, Bolze, Alexandre, additional, Khan, Taushif, additional, Gervais, Adrian, additional, Krüger, Renate, additional, Völler, Mirjam, additional, Palterer, Boaz, additional, Sadeghi-Shabestari, Mahnaz, additional, Langlois de Septenville, Anne, additional, Schramm, Chaim A., additional, Shah, Sanjana, additional, Tello-Cajiao, John J., additional, Pala, Francesca, additional, Amini, Kayla, additional, Campos, Jose S., additional, Lima, Noemia Santana, additional, Eriksson, Daniel, additional, Lévy, Romain, additional, Seeleuthner, Yoann, additional, Jyonouchi, Soma, additional, Ata, Manar, additional, Al Ali, Fatima, additional, Deswarte, Caroline, additional, Pereira, Anaïs, additional, Mégret, Jérôme, additional, Le Voyer, Tom, additional, Bastard, Paul, additional, Berteloot, Laureline, additional, Dussiot, Michaël, additional, Vladikine, Natasha, additional, Cardenas, Paula P., additional, Jouanguy, Emmanuelle, additional, Alqahtani, Mashael, additional, Hasan, Amal, additional, Thanaraj, Thangavel Alphonse, additional, Rosain, Jérémie, additional, Al Qureshah, Fahd, additional, Sabato, Vito, additional, Alyanakian, Marie Alexandra, additional, Leruez-Ville, Marianne, additional, Rozenberg, Flore, additional, Haddad, Elie, additional, Regueiro, Jose R., additional, Toribio, Maria L., additional, Kelsen, Judith R., additional, Salehi, Mansoor, additional, Nasiri, Shahram, additional, Torabizadeh, Mehdi, additional, Rokni-Zadeh, Hassan, additional, Changi-Ashtiani, Majid, additional, Vatandoost, Nasimeh, additional, Moravej, Hossein, additional, Akrami, Seyed Mohammad, additional, Mazloomrezaei, Mohsen, additional, Cobat, Aurélie, additional, Meyts, Isabelle, additional, Toyofuku, Etsushi, additional, Nishimura, Madoka, additional, Moriya, Kunihiko, additional, Mizukami, Tomoyuki, additional, Imai, Kohsuke, additional, Abel, Laurent, additional, Malissen, Bernard, additional, Al-Mulla, Fahd, additional, Alkuraya, Fowzan Sami, additional, Parvaneh, Nima, additional, von Bernuth, Horst, additional, Beetz, Christian, additional, Davi, Frédéric, additional, Douek, Daniel C., additional, Cheynier, Rémi, additional, Langlais, David, additional, Landegren, Nils, additional, Marr, Nico, additional, Morio, Tomohiro, additional, Shahrooei, Mohammad, additional, Schrijvers, Rik, additional, Henrickson, Sarah E., additional, Luche, Hervé, additional, Notarangelo, Luigi D., additional, Casanova, Jean-Laurent, additional, and Béziat, Vivien, additional

Published
2024
Full Text
View/download PDF

23. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency

Author

Castiello, Maria Carmina, primary, Brandas, Chiara, additional, Ferrari, Samuele, additional, Porcellini, Simona, additional, Sacchetti, Nicolò, additional, Canarutto, Daniele, additional, Draghici, Elena, additional, Merelli, Ivan, additional, Barcella, Matteo, additional, Pelosi, Gabriele, additional, Vavassori, Valentina, additional, Varesi, Angelica, additional, Jacob, Aurelien, additional, Scala, Serena, additional, Basso Ricci, Luca, additional, Paulis, Marianna, additional, Strina, Dario, additional, Di Verniere, Martina, additional, Sergi Sergi, Lucia, additional, Serafini, Marta, additional, Holland, Steven M., additional, Bergerson, Jenna R. E., additional, De Ravin, Suk See, additional, Malech, Harry L., additional, Pala, Francesca, additional, Bosticardo, Marita, additional, Brombin, Chiara, additional, Cugnata, Federica, additional, Calzoni, Enrica, additional, Crooks, Gay M., additional, Notarangelo, Luigi D., additional, Genovese, Pietro, additional, Naldini, Luigi, additional, and Villa, Anna, additional

Published
2024
Full Text
View/download PDF

25. Lentiviral gene therapy corrects platelet phenotype and function in patients with Wiskott-Aldrich syndrome

Author

Sereni, Lucia, Castiello, Maria Carmina, Di Silvestre, Dario, Della Valle, Patrizia, Brombin, Chiara, Ferrua, Francesca, Cicalese, Maria Pia, Pozzi, Loris, Migliavacca, Maddalena, Bernardo, Maria Ester, Pignata, Claudio, Farah, Roula, Notarangelo, Lucia Dora, Marcus, Nufar, Cattaneo, Lorella, Spinelli, Marco, Giannelli, Stefania, Bosticardo, Marita, van Rossem, Koen, D'Angelo, Armando, Aiuti, Alessandro, Mauri, Pierluigi, and Villa, Anna

Published
2019
Full Text
View/download PDF

26. Mulibrey nanism and immunological complications: a comprehensive case report and literature review

Author

Gazzin, Andrea, primary, Pala, Francesca, additional, Bosticardo, Marita, additional, Niemela, Julie, additional, Stoddard, Jennifer, additional, Biasin, Eleonora, additional, Quarello, Paola, additional, Carli, Diana, additional, Ferroni, Francesca, additional, Delmonte, Ottavia M., additional, Montin, Davide, additional, Rosenzweig, Sergio D., additional, Licciardi, Francesco, additional, and Notarangelo, Luigi D., additional

Published
2023
Full Text
View/download PDF

27. Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals.

Author

Delmonte, Ottavia M., primary, Oguz, Cihan, additional, Dobbs, Kerry, additional, Myint-Hpu, Katherine, additional, Palterer, Boaz, additional, Abers, Michael S., additional, Draper, Deborah, additional, Truong, Meng, additional, Kaplan, Ian M., additional, Gittelman, Rachel M., additional, Zhang, Yu, additional, Rosen, Lindsey B., additional, Snow, Andrew L., additional, Dalgard, Clifton L., additional, Burbelo, Peter D., additional, Imberti, Luisa, additional, Sottini, Alessandra, additional, Quiros-Roldan, Eugenia, additional, Castelli, Francesco, additional, Rossi, Camillo, additional, Brugnoni, Duilio, additional, Biondi, Andrea, additional, Bettini, Laura Rachele, additional, D’Angio’, Mariella, additional, Bonfanti, Paolo, additional, Anderson, Megan V., additional, Saracino, Annalisa, additional, Chironna, Maria, additional, Di Stefano, Mariantonietta, additional, Fiore, Jose Ramon, additional, Santantonio, Teresa, additional, Castagnoli, Riccardo, additional, Marseglia, Gian Luigi, additional, Magliocco, Mary, additional, Bosticardo, Marita, additional, Pala, Francesca, additional, Shaw, Elana, additional, Matthews, Helen, additional, Weber, Sarah E., additional, Xirasagar, Sandhya, additional, Barnett, Jason, additional, Oler, Andrew J., additional, Dimitrova, Dimana, additional, Bergerson, Jenna R.E., additional, McDermott, David H., additional, Rao, V. Koneti, additional, Murphy, Philip M., additional, Holland, Steven M., additional, Lisco, Andrea, additional, Su, Helen C., additional, Lionakis, Michail S., additional, Cohen, Jeffrey I., additional, Freeman, Alexandra F., additional, Snyder, Thomas M., additional, Lack, Justin, additional, and Notarangelo, Luigi D., additional

Published
2023
Full Text
View/download PDF

28. A spatial human thymus cell atlas mapped to a continuous tissue axis

Author

Yayon, Nadav, primary, Kedlian, Veronika R., additional, Boehme, Lena, additional, Suo, Chenqu, additional, Wachter, Brianna, additional, Beuschel, Rebecca T., additional, Amsalem, Oren, additional, Polanski, Krzysztof, additional, Koplev, Simon, additional, Tuck, Elizabeth, additional, Dann, Emma, additional, Van Hulle, Jolien, additional, Perera, Shani, additional, Putteman, Tom, additional, Predeus, Alexander V., additional, Dabrowska, Monika, additional, Richardson, Laura, additional, Tudor, Catherine, additional, Kreins, Alexandra Y., additional, Engelbert, Justin, additional, Stephenson, Emily, additional, Kleshchevnikov, Vitalii, additional, De Rita, Fabrizio, additional, Crossland, David, additional, Bosticardo, Marita, additional, Pala, Francesca, additional, Prigmore, Elena, additional, Chipampe, Nana-Jane, additional, Prete, Martin, additional, Fei, Lijiang, additional, To, Ken, additional, Barker, Roger A., additional, He, Xiaoling, additional, Van Nieuwerburgh, Filip, additional, Bayraktar, Omer, additional, Patel, Minal, additional, Davies, Graham E., additional, Haniffa, Muzlifah A., additional, Uhlmann, Virginie, additional, Notarangelo, Luigi D., additional, Germain, Ronald N., additional, Radtke, Andrea J., additional, Marioni, John C., additional, Taghon, Tom, additional, and Teichmann, Sarah A., additional

Published
2023
Full Text
View/download PDF

29. Characterization of the antispike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies

Author

Zendt, Mackenzie, primary, Bustos Carrillo, Fausto A., additional, Kelly, Sophie, additional, Saturday, Taylor, additional, DeGrange, Maureen, additional, Ginigeme, Anita, additional, Wu, Lurline, additional, Callier, Viviane, additional, Ortega-Villa, Ana, additional, Faust, Mondreakest, additional, Chang-Rabley, Emma, additional, Bugal, Kara, additional, Kenney, Heather, additional, Khil, Pavel, additional, Youn, Jung-Ho, additional, Osei, Gloria, additional, Regmi, Pravesh, additional, Anderson, Victoria, additional, Bosticardo, Marita, additional, Daub, Janine, additional, DiMaggio, Thomas, additional, Kreuzburg, Samantha, additional, Pala, Francesca, additional, Pfister, Justina, additional, Treat, Jennifer, additional, Ulrick, Jean, additional, Karkanitsa, Maria, additional, Kalish, Heather, additional, Kuhns, Douglas B., additional, Priel, Debra L., additional, Fink, Danielle L., additional, Tsang, John S., additional, Sparks, Rachel, additional, Uzel, Gulbu, additional, Waldman, Meryl A., additional, Zerbe, Christa S., additional, Delmonte, Ottavia M., additional, Bergerson, Jenna R. E., additional, Das, Sanchita, additional, Freeman, Alexandra F., additional, Lionakis, Michail S., additional, Sadtler, Kaitlyn, additional, van Doremalen, Neeltje, additional, Munster, Vincent, additional, Notarangelo, Luigi D., additional, Holland, Steven M., additional, and Ricotta, Emily E., additional

Published
2023
Full Text
View/download PDF

30. Corrigendum to “Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients” [Clinical Immunology 255 (2023) 109757]

Author

Yakici, Nalan, primary, Kreins, Alexandra Y., additional, Catak, Mehmet Cihangir, additional, Babayeva, Royala, additional, Erman, Baran, additional, Kenney, Heather, additional, Eke-Gungor, Hatice, additional, Cea, Pablo A., additional, Kawai, Tomoki, additional, Bosticardo, Marita, additional, Delmonte, Ottavia Maria, additional, Adams, Stuart, additional, Fan, Yu-Tong, additional, Pala, Francesca, additional, Turkyilmaz, Ayberk, additional, Howley, Evey, additional, Worth, Austen, additional, Kot, Hakan, additional, Sefer, Asena Pinar, additional, Kara, Altan, additional, Bulutoglu, Alper, additional, Bilgic-Eltan, Sevgi, additional, Yorgun Altunbas, Melek, additional, Bayram Catak, Feyza, additional, Karakus, Ibrahim Serhat, additional, Karatay, Emrah, additional, Tekeoglu, Sidem Didar, additional, Eser, Metin, additional, Albayrak, Davut, additional, Citli, Senol, additional, Kiykim, Ayca, additional, Karakoc-Aydiner, Elif, additional, Ozen, Ahmet, additional, Ghosh, Sujal, additional, Gohlke, Holger, additional, Orhan, Fazil, additional, Notarangelo, Luigi D., additional, Davies, E. Graham, additional, and Baris, Safa, additional

Published
2023
Full Text
View/download PDF

31. 213 IKAROS negatively regulate memory T cell formation in humans

Author

Tagirasa, Ravichandra, Kueh, HyeSun, Bosticardo, Marita, Pala, Francesca, Amini, Kayla, Anaya, Eduardo, Stoddard, Jennifer, Niemela, Julie, Alsina, Laia, Seoane, Mario Framil, Dimitrova, Dimana, Oleastro, Matias, Bouso, Carolina, LWasserman, Richard, Notarangelo, Luigi, and Rosenzweig, Sergio

Published
2024
Full Text
View/download PDF

32. 210 A multimorphic variant in ThPOK causes a novel human disease characterized by T cell immune developmental abnormalities, immunodysregulation, atopy, and organ fibrosis

Author

Vaseghi-Shanjani, Maryam, Sharma, Mehul, Yousefi, Pariya, Samra, Simran, Laverty, Kaitlin, Jolma, Arttu, Golding, Liam, Razavi, Rozita, Yang, Ally, Albu, Mihai, Lee, Anna, Tan, Ryan, Richmond, Phillip, Bosticardo, Marita, Rayment, Jonathan, Yang, Connie, Hildebrand, Kyla, Brager, Rae, Demos, Michelle, Lau, Yu-Lung, Notarangelo, Luigi, Hughes, Timothy, Bosselut, Remy, Biggs, Catherine, and Turvey, Stuart E.

Published
2024
Full Text
View/download PDF

33. Expanded microbiome niches of RAG-deficient patients

Author

Blaustein, Ryan A., primary, Shen, Zeyang, additional, Kashaf, Sara Saheb, additional, Lee-Lin, ShihQueen, additional, Conlan, Sean, additional, Bosticardo, Marita, additional, Delmonte, Ottavia M., additional, Holmes, Cassandra J., additional, Taylor, Monica E., additional, Banania, Glenna, additional, Nagao, Keisuke, additional, Dimitrova, Dimana, additional, Kanakry, Jennifer A., additional, Su, Helen, additional, Holland, Steven M., additional, Bergerson, Jenna R.E., additional, Freeman, Alexandra F., additional, Notarangelo, Luigi D., additional, Kong, Heidi H., additional, Segre, Julia A., additional, Thomas, Jim, additional, Mullikin, James, additional, Young, Alice, additional, Bouffard, Gerry, additional, Barnabas, Betty, additional, Brooks, Shelise, additional, Buchter, Chloe, additional, Crawford, Juyun, additional, Han, Joel, additional, Ho, Shi-ling, additional, Legaspi, Richelle, additional, Maduro, Quino, additional, Marfani, Holly, additional, Montemayor, Casandra, additional, Schandler, Karen, additional, Schmidt, Brian, additional, Sison, Christina, additional, Stantripop, Mal, additional, Black, Sean, additional, Dekhtyar, Mila, additional, Masiello, Cathy, additional, McDowell, Jenny, additional, Park, Morgan, additional, Thomas, Pam, additional, and Vemulapalli, Meg, additional

Published
2023
Full Text
View/download PDF

35. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

Author

Locci, Michela, Draghici, Elena, Marangoni, Francesco, Bosticardo, Marita, Catucci, Marco, Aiuti, Alessandro, Cancrini, Caterina, Marodi, Laszlo, Espanol, Teresa, Bredius, Robbert GM, Thrasher, Adrian J, Schulz, Ansgar, Litzman, Jiri, Roncarolo, Maria Grazia, Casorati, Giulia, Dellabona, Paolo, and Villa, Anna

Subjects
Genetics, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Cytokines, Flow Cytometry, Humans, Hyaluronan Receptors, Lymphocyte Activation, Mice, Mice, Knockout, Mutation, Natural Killer T-Cells, Phenotype, Wiskott-Aldrich Syndrome, Medical and Health Sciences, Immunology
Abstract

The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was(-/-) mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was(-/-) mice as compared with wild-type controls. Moreover analysis of was(-/-) iNKT cell maturation revealed a complete arrest at the CD44(+) NK1.1(-) intermediate stage. Notably, generation of BM chimeras demonstrated a was(-/-) iNKT cell-autonomous developmental defect. was(-/-) iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon gamma upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology.

Published
2009

37. Correlation between levels of anti-cytokine antibodies, recombination activity of the mutant RAG proteins and clinical phenotype in patients with RAG deficiency

Author

Notarangelo, Luigi, primary, Kenney, Heather, additional, Rosen, Lindsey, additional, Bosticardo, Marita, additional, Delmonte, Ottavia, additional, Pala, Francesca, additional, Bergerson, Jenna, additional, Dimitrova, Dimana, additional, Freeman, Alexandra, additional, and Holland, Steven, additional

Published
2023
Full Text
View/download PDF

40. Gut immunopathological signatures in Rag1 hypomorphic mice

Author

Pala, Francesca, primary, Castagnoli, Riccardo, additional, Lim, Ai Ing, additional, Bosticardo, Marita, additional, Fontana, Elena, additional, Oguz, Cihan, additional, Subramanian, Poorani, additional, Pittaluga, Stefania, additional, Belkaid, Yasmine, additional, and Notarangelo, Luigi, additional

Published
2023
Full Text
View/download PDF

44. Separating the wheat from the chaff in asthma and bronchiectasis: the saga trajectory of a patient with adult-onset RAG1 deficiency

Author

Lopez, Maria Chitty, primary, Yilmaz, Melis, additional, Diaz-Cabrera, Natalie M., additional, Saco, Tara, additional, Ismael, Leah, additional, Sotoudeh, Shannon, additional, Bindernagel, Constance, additional, Ujhazi, Boglarka, additional, Gordon, Sumai, additional, Potts, David Evan, additional, Danziger, Roger, additional, Bosticardo, Marita, additional, Kenney, Heather, additional, Illes, Peter, additional, Lee, Sena, additional, Harris, Megan, additional, Cuellar-Rodriguez, Jennifer, additional, Patel, Kapil N., additional, Csomos, Krisztian, additional, Dimitrova, Dimana, additional, Kanakry, Jennifer A., additional, Notarangelo, Luigi D., additional, and Walter, Jolan E., additional

Published
2023
Full Text
View/download PDF

45. Correction to: Gene Editing Rescues in Vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System

Author

Gardner, Cameron L., Pavel-Dinu, Mara, Dobbs, Kerry, Bosticardo, Marita, Reardon, Paul K., Lack, Justin, DeRavin, Suk See, Le, Kent, Bello, Ezekiel, Pala, Francesca, Delmonte, Ottavia M., Malech, Harry, Montel-Hagen, Amelie, Crooks, Gay, Acuto, Oreste, Porteus, Matthew H., and Notarangelo, Luigi D.

Published
2021
Full Text
View/download PDF

47. CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells

Author

Brault, Julie, primary, Liu, Taylor, additional, Liu, Siyuan, additional, Lawson, Amanda, additional, Choi, Uimook, additional, Kozhushko, Nikita, additional, Bzhilyanskaya, Vera, additional, Pavel-Dinu, Mara, additional, Meis, Ronald J., additional, Eckhaus, Michael A., additional, Burkett, Sandra S., additional, Bosticardo, Marita, additional, Kleinstiver, Benjamin P., additional, Notarangelo, Luigi D., additional, Lazzarotto, Cicera R., additional, Tsai, Shengdar Q., additional, Wu, Xiaolin, additional, Dahl, Gary A., additional, Porteus, Matthew H., additional, Malech, Harry L., additional, and De Ravin, Suk See, additional

Published
2023
Full Text
View/download PDF

49. FOXI3 haploinsufficiency contributes to low T-cell receptor excision circles and T-cell lymphopenia

Author

Ghosh, Rajarshi, primary, Bosticardo, Marita, additional, Singh, Sunita, additional, Similuk, Morgan, additional, Delmonte, Ottavia M., additional, Pala, Francesca, additional, Peng, Christine, additional, Jodarski, Colleen, additional, Keller, Michael D., additional, Chinn, Ivan K., additional, Groves, Andrew K., additional, Notarangelo, Luigi D., additional, Walkiewicz, Magdalena A., additional, Chinen, Javier, additional, and Bundy, Vanessa, additional

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results