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2. Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs

Author

Framme, Jenny Lingman, Lundqvist, Christina, Lundell, Anna-Carin, van Schouwenburg, Pauline A., Lemarquis, Andri L., Thörn, Karolina, Lindgren, Susanne, Gudmundsdottir, Judith, Lundberg, Vanja, Degerman, Sofie, Zetterström, Rolf H., Borte, Stephan, Hammarström, Lennart, Telemo, Esbjörn, Hultdin, Magnus, van der Burg, Mirjam, Fasth, Anders, Oskarsdóttir, Sólveig, and Ekwall, Olov

Published
2022
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5. Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections

Author

Wentink, Marjolein, Dalm, Virgil, Lankester, Arjan C., van Schouwenburg, Pauline A., Schölvinck, Liesbeth, Kalina, Tomas, Zachova, Radana, Sediva, Anna, Lambeck, Annechien, Pico-Knijnenburg, Ingrid, van Dongen, Jacques J.M., Pac, Malgorzata, Bernatowska, Ewa, van Hagen, Martin, Driessen, Gertjan, and van der Burg, Mirjam

Published
2017
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7. Deciphering imprints of impaired memory B-cell maturation in germinal centers of three patients with common variable immunodeficiency

Author

van Schouwenburg, Pauline, primary, Unger, Susanne, additional, Payne, Kathryn J., additional, Kaiser, Fabian M. P., additional, Pico-Knijnenburg, Ingrid, additional, Pfeiffer, Jens, additional, Hausmann, Oliver, additional, Friedmann, David, additional, Erbel, Michelle, additional, Seidl, Maximilian, additional, van Zessen, David, additional, Stubbs, Andrew P., additional, van der Burg, Mirjam, additional, and Warnatz, Klaus, additional

Published
2022
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9. The TH1 phenotype of follicular helper T cells indicates an IFN-γ–associated immune dysregulation in patients with CD21low common variable immunodeficiency

Author

Unger, Susanne, Seidl, Maximilian, van Schouwenburg, Pauline, Rakhmanov, Mirzokhid, Bulashevska, Alla, Frede, Natalie, Grimbacher, Bodo, Pfeiffer, Jens, Schrenk, Klaudia, Munoz, Luis, Hanitsch, Leif, Stumpf, Ina, Kaiser, Fabian, Hausmann, Oliver, Kollert, Florian, Goldacker, Sigune, van der Burg, Mirjam, Keller, Baerbel, and Warnatz, Klaus

Published
2018
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10. Deciphering imprints of impaired memory B-cell maturation in germinal centers of three patients with common variable immunodeficiency

Author

van Schouwenburg, Pauline, Unger, Susanne, Payne, Kathryn J., Kaiser, Fabian M.P., Pico-Knijnenburg, Ingrid, Pfeiffer, Jens, Hausmann, Oliver, Friedmann, David, Erbel, Michelle, Seidl, Maximilian, van Zessen, David, Stubbs, Andrew P., van der Burg, Mirjam, Warnatz, Klaus, van Schouwenburg, Pauline, Unger, Susanne, Payne, Kathryn J., Kaiser, Fabian M.P., Pico-Knijnenburg, Ingrid, Pfeiffer, Jens, Hausmann, Oliver, Friedmann, David, Erbel, Michelle, Seidl, Maximilian, van Zessen, David, Stubbs, Andrew P., van der Burg, Mirjam, and Warnatz, Klaus

Abstract

Common variable immunodeficiency (CVID), characterized by recurrent infections, low serum class-switched immunoglobulin isotypes, and poor antigen-specific antibody responses, comprises a heterogeneous patient population in terms of clinical presentation and underlying etiology. The diagnosis is regularly associated with a severe decrease of germinal center (GC)-derived B-cell populations in peripheral blood. However, data from B-cell differentiation within GC is limited. We present a multiplex approach combining histology, flow cytometry, and B-cell receptor repertoire analysis of sorted GC B-cell populations allowing the modeling of distinct disturbances in GCs of three CVID patients. Our results reflect pathophysiological heterogeneity underlying the reduced circulating pool of post-GC memory B cells and plasmablasts in the three patients. In patient 1, quantitative and qualitative B-cell development in GCs is relatively normal. In patient 2, irregularly shaped GCs are associated with reduced somatic hypermutation (SHM), antigen selection, and class-switching, while in patient 3, high SHM, impaired antigen selection, and class-switching with large single clones imply increased re-cycling of cells within the irregularly shaped GCs. In the lymph nodes of patients 2 and 3, only limited numbers of memory B cells and plasma cells are formed. While reduced numbers of circulating post GC B cells are a general phenomenon in CVID, the integrated approach exemplified distinct defects during GC maturation ranging from near normal morphology and function to severe disturbances with different facets of impaired maturation of memory B cells and/or plasma cells. Integrated dissection of disturbed GC B-cell maturation by histology, flow cytometry, and BCR repertoire analysis contributes to unraveling defects in the essential steps during memory formation.

Published
2022

12. Tandem Substitutions in Somatic Hypermutation

Author

Sepúlveda-Yáñez, Julieta H., primary, Alvarez Saravia, Diego, additional, Pilzecker, Bas, additional, van Schouwenburg, Pauline A., additional, van den Burg, Mirjam, additional, Veelken, Hendrik, additional, Navarrete, Marcelo A., additional, Jacobs, Heinz, additional, and Koning, Marvyn T., additional

Published
2022
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13. Tandem Substitutions in Somatic Hypermutation

Author

Koning, Marvyn T., primary, Sepulveda Yanez, Julieta Haydee, additional, Alvarez-Saravia, Diego, additional, Pilzecker, Bas, additional, Van Schouwenburg, Pauline, additional, van den Burg, Mirjam, additional, Navarrete, Marcelo A., additional, Jacobs, Heinz, additional, and Veelken, Hendrik, additional

Published
2021
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25. Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans

Author

IJspeert, Hanna, primary, van Schouwenburg, Pauline A., additional, Pico-Knijnenburg, Ingrid, additional, Loeffen, Jan, additional, Brugieres, Laurence, additional, Driessen, Gertjan J., additional, Blattmann, Claudia, additional, Suerink, Manon, additional, Januszkiewicz-Lewandowska, Danuta, additional, Azizi, Amedeo A., additional, Seidel, Marcus G., additional, Jacobs, Heinz, additional, and van der Burg, Mirjam, additional

Published
2019
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28. A kindred with mutant IKAROS and autoimmunity

Author

Van Nieuwenhove, Erika, primary, Garcia-Perez, Josselyn E., additional, Helsen, Christine, additional, Rodriguez, Princess D., additional, van Schouwenburg, Pauline A., additional, Dooley, James, additional, Schlenner, Susan, additional, van der Burg, Mirjam, additional, Verhoeyen, Els, additional, Gijsbers, Rik, additional, Frietze, Seth, additional, Schjerven, Hilde, additional, Meyts, Isabelle, additional, Claessens, Frank, additional, Humblet-Baron, Stephanie, additional, Wouters, Carine, additional, and Liston, Adrian, additional

Published
2018
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31. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, McVean, Gilean, Taylor, Jenny C., Martin, Hilary C., Lise, Stefano, Broxholme, John, Cazier, Jean-Baptiste, Rimmer, Andy, Kanapin, Alexander, Lunter, Gerton, Fiddy, Simon, Allan, Chris, Aricescu, A. Radu, Attar, Moustafa, Babbs, Christian, Becq, Jennifer, Beeson, David, Bento, Celeste, Bignell, Patricia, Blair, Edward, Buckle, Veronica J., Bull, Katherine, Cais, Ondrej, Cario, Holger, Chapel, Helen, Copley, Richard R., Cornall, Richard, Craft, Jude, Dahan, Karin, Davenport, Emma E., Dendrou, Calliope, Devuyst, Olivier, Fenwick, Aimée L., Flint, Jonathan, Fugger, Lars, Gilbert, Rodney D., Goriely, Anne, Green, Angie, Greger, Ingo H., Grocock, Russell, Gruszczyk, Anja V., Hastings, Robert, Hatton, Edouard, Higgs, Doug, Hill, Adrian, Holmes, Chris, Howard, Malcolm, Hughes, Linda, Humburg, Peter, Johnson, David, Karpe, Fredrik, Kingsbury, Zoya, Kini, Usha, Knight, Julian C., Krohn, Jonathan, Lamble, Sarah, Langman, Craig, Lonie, Lorne, Luck, Joshua, McCarthy, Davis, McGowan, Simon J., McMullin, Mary Frances, Miller, Kerry A., Murray, Lisa, Németh, Andrea H., Nesbit, M. Andrew, Nutt, David, Ormondroyd, Elizabeth, Bang Oturai, Annette, Pagnamenta, Alistair, Patel, Smita Y., Percy, Melanie, Petousi, Nayia, Piazza, Paolo, Piret, Sian E., Polanco-Echeverry, Guadalupe, Popitsch, Niko, Powrie, Fiona, Pugh, Chris, Quek, Lynn, Robbins, Peter A., Robson, Kathryn, Russo, Alexandra, Sahgal, Natasha, Van Schouwenburg, Pauline A., Schuh, Anna, Silverman, Earl, Simmons, Alison, Sorensen, Per Soelberg, Sweeney, Elizabeth, Taylor, John, Thakker, Rajesh V., Tomlinson, Ian, Trebes, Amy, Twigg, Stephen R. F., Uhlig, Holm H., Vyas, Paresh, Vyse, Tim, Wall, Steven A., Watkins, Hugh, Whyte, Michael P., Witty, Lorna, Wright, Ben, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, McVean, Gilean, Taylor, Jenny C., Martin, Hilary C., Lise, Stefano, Broxholme, John, Cazier, Jean-Baptiste, Rimmer, Andy, Kanapin, Alexander, Lunter, Gerton, Fiddy, Simon, Allan, Chris, Aricescu, A. Radu, Attar, Moustafa, Babbs, Christian, Becq, Jennifer, Beeson, David, Bento, Celeste, Bignell, Patricia, Blair, Edward, Buckle, Veronica J., Bull, Katherine, Cais, Ondrej, Cario, Holger, Chapel, Helen, Copley, Richard R., Cornall, Richard, Craft, Jude, Dahan, Karin, Davenport, Emma E., Dendrou, Calliope, Devuyst, Olivier, Fenwick, Aimée L., Flint, Jonathan, Fugger, Lars, Gilbert, Rodney D., Goriely, Anne, Green, Angie, Greger, Ingo H., Grocock, Russell, Gruszczyk, Anja V., Hastings, Robert, Hatton, Edouard, Higgs, Doug, Hill, Adrian, Holmes, Chris, Howard, Malcolm, Hughes, Linda, Humburg, Peter, Johnson, David, Karpe, Fredrik, Kingsbury, Zoya, Kini, Usha, Knight, Julian C., Krohn, Jonathan, Lamble, Sarah, Langman, Craig, Lonie, Lorne, Luck, Joshua, McCarthy, Davis, McGowan, Simon J., McMullin, Mary Frances, Miller, Kerry A., Murray, Lisa, Németh, Andrea H., Nesbit, M. Andrew, Nutt, David, Ormondroyd, Elizabeth, Bang Oturai, Annette, Pagnamenta, Alistair, Patel, Smita Y., Percy, Melanie, Petousi, Nayia, Piazza, Paolo, Piret, Sian E., Polanco-Echeverry, Guadalupe, Popitsch, Niko, Powrie, Fiona, Pugh, Chris, Quek, Lynn, Robbins, Peter A., Robson, Kathryn, Russo, Alexandra, Sahgal, Natasha, Van Schouwenburg, Pauline A., Schuh, Anna, Silverman, Earl, Simmons, Alison, Sorensen, Per Soelberg, Sweeney, Elizabeth, Taylor, John, Thakker, Rajesh V., Tomlinson, Ian, Trebes, Amy, Twigg, Stephen R. F., Uhlig, Holm H., Vyas, Paresh, Vyse, Tim, Wall, Steven A., Watkins, Hugh, Whyte, Michael P., Witty, Lorna, and Wright, Ben

Abstract

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Published
2015

32. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

Author

Taylor, Jenny C, Martin, Hilary C, Lise, Stefano, Broxholme, John, Cazier, Jean-Baptiste, Rimmer, Andy, Kanapin, Alexander, Lunter, Gerton, Fiddy, Simon, Allan, Chris, Aricescu, A Radu, Attar, Moustafa, Babbs, Christian, Becq, Jennifer, Beeson, David, Bento, Celeste, Bignell, Patricia, Blair, Edward, Buckle, Veronica J, Bull, Katherine, Cais, Ondrej, Cario, Holger, Chapel, Helen, Copley, Richard R, Cornall, Richard, Craft, Jude, Dahan, Karin, Davenport, Emma E, Dendrou, Calliope, Devuyst, Olivier, Fenwick, Aimée L, Flint, Jonathan, Fugger, Lars, Gilbert, Rodney D, Goriely, Anne, Green, Angie, Greger, Ingo H, Grocock, Russell, Gruszczyk, Anja V, Hastings, Robert, Hatton, Edouard, Higgs, Doug, Hill, Adrian, Holmes, Chris, Howard, Malcolm, Hughes, Linda, Humburg, Peter, Johnson, David, Karpe, Fredrik, Kingsbury, Zoya, Kini, Usha, Knight, Julian C, Krohn, Jonathan, Lamble, Sarah, Langman, Craig, Lonie, Lorne, Luck, Joshua, McCarthy, Davis, McGowan, Simon J, McMullin, Mary Frances, Miller, Kerry A, Murray, Lisa, Németh, Andrea H, Nesbit, M Andrew, Nutt, David, Ormondroyd, Elizabeth, Oturai, Annette Bang, Pagnamenta, Alistair, Patel, Smita Y, Percy, Melanie, Petousi, Nayia, Piazza, Paolo, Piret, Sian E, Polanco-Echeverry, Guadalupe, Popitsch, Niko, Powrie, Fiona, Pugh, Chris, Quek, Lynn, Robbins, Peter A, Robson, Kathryn, Russo, Alexandra, Sahgal, Natasha, van Schouwenburg, Pauline A, Schuh, Anna, Silverman, Earl, Simmons, Alison, Sørensen, Per Soelberg, Sweeney, Elizabeth, Taylor, John, Thakker, Rajesh V, Tomlinson, Ian, Trebes, Amy, Twigg, Stephen R F, Uhlig, Holm H, Vyas, Paresh, Vyse, Tim, Wall, Steven A, Watkins, Hugh, Whyte, Michael P, Witty, Lorna, Wright, Ben, Yau, Chris, Buck, David, Humphray, Sean, Ratcliffe, Peter J, Bell, John I, Wilkie, Andrew O M, Bentley, David, Donnelly, Peter, McVean, Gilean, Taylor, Jenny C, Martin, Hilary C, Lise, Stefano, Broxholme, John, Cazier, Jean-Baptiste, Rimmer, Andy, Kanapin, Alexander, Lunter, Gerton, Fiddy, Simon, Allan, Chris, Aricescu, A Radu, Attar, Moustafa, Babbs, Christian, Becq, Jennifer, Beeson, David, Bento, Celeste, Bignell, Patricia, Blair, Edward, Buckle, Veronica J, Bull, Katherine, Cais, Ondrej, Cario, Holger, Chapel, Helen, Copley, Richard R, Cornall, Richard, Craft, Jude, Dahan, Karin, Davenport, Emma E, Dendrou, Calliope, Devuyst, Olivier, Fenwick, Aimée L, Flint, Jonathan, Fugger, Lars, Gilbert, Rodney D, Goriely, Anne, Green, Angie, Greger, Ingo H, Grocock, Russell, Gruszczyk, Anja V, Hastings, Robert, Hatton, Edouard, Higgs, Doug, Hill, Adrian, Holmes, Chris, Howard, Malcolm, Hughes, Linda, Humburg, Peter, Johnson, David, Karpe, Fredrik, Kingsbury, Zoya, Kini, Usha, Knight, Julian C, Krohn, Jonathan, Lamble, Sarah, Langman, Craig, Lonie, Lorne, Luck, Joshua, McCarthy, Davis, McGowan, Simon J, McMullin, Mary Frances, Miller, Kerry A, Murray, Lisa, Németh, Andrea H, Nesbit, M Andrew, Nutt, David, Ormondroyd, Elizabeth, Oturai, Annette Bang, Pagnamenta, Alistair, Patel, Smita Y, Percy, Melanie, Petousi, Nayia, Piazza, Paolo, Piret, Sian E, Polanco-Echeverry, Guadalupe, Popitsch, Niko, Powrie, Fiona, Pugh, Chris, Quek, Lynn, Robbins, Peter A, Robson, Kathryn, Russo, Alexandra, Sahgal, Natasha, van Schouwenburg, Pauline A, Schuh, Anna, Silverman, Earl, Simmons, Alison, Sørensen, Per Soelberg, Sweeney, Elizabeth, Taylor, John, Thakker, Rajesh V, Tomlinson, Ian, Trebes, Amy, Twigg, Stephen R F, Uhlig, Holm H, Vyas, Paresh, Vyse, Tim, Wall, Steven A, Watkins, Hugh, Whyte, Michael P, Witty, Lorna, Wright, Ben, Yau, Chris, Buck, David, Humphray, Sean, Ratcliffe, Peter J, Bell, John I, Wilkie, Andrew O M, Bentley, David, Donnelly, Peter, and McVean, Gilean

Abstract

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Published
2015

34. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

Author

Taylor, Jenny C, primary, Martin, Hilary C, additional, Lise, Stefano, additional, Broxholme, John, additional, Cazier, Jean-Baptiste, additional, Rimmer, Andy, additional, Kanapin, Alexander, additional, Lunter, Gerton, additional, Fiddy, Simon, additional, Allan, Chris, additional, Aricescu, A Radu, additional, Attar, Moustafa, additional, Babbs, Christian, additional, Becq, Jennifer, additional, Beeson, David, additional, Bento, Celeste, additional, Bignell, Patricia, additional, Blair, Edward, additional, Buckle, Veronica J, additional, Bull, Katherine, additional, Cais, Ondrej, additional, Cario, Holger, additional, Chapel, Helen, additional, Copley, Richard R, additional, Cornall, Richard, additional, Craft, Jude, additional, Dahan, Karin, additional, Davenport, Emma E, additional, Dendrou, Calliope, additional, Devuyst, Olivier, additional, Fenwick, Aimée L, additional, Flint, Jonathan, additional, Fugger, Lars, additional, Gilbert, Rodney D, additional, Goriely, Anne, additional, Green, Angie, additional, Greger, Ingo H, additional, Grocock, Russell, additional, Gruszczyk, Anja V, additional, Hastings, Robert, additional, Hatton, Edouard, additional, Higgs, Doug, additional, Hill, Adrian, additional, Holmes, Chris, additional, Howard, Malcolm, additional, Hughes, Linda, additional, Humburg, Peter, additional, Johnson, David, additional, Karpe, Fredrik, additional, Kingsbury, Zoya, additional, Kini, Usha, additional, Knight, Julian C, additional, Krohn, Jonathan, additional, Lamble, Sarah, additional, Langman, Craig, additional, Lonie, Lorne, additional, Luck, Joshua, additional, McCarthy, Davis, additional, McGowan, Simon J, additional, McMullin, Mary Frances, additional, Miller, Kerry A, additional, Murray, Lisa, additional, Németh, Andrea H, additional, Nesbit, M Andrew, additional, Nutt, David, additional, Ormondroyd, Elizabeth, additional, Oturai, Annette Bang, additional, Pagnamenta, Alistair, additional, Patel, Smita Y, additional, Percy, Melanie, additional, Petousi, Nayia, additional, Piazza, Paolo, additional, Piret, Sian E, additional, Polanco-Echeverry, Guadalupe, additional, Popitsch, Niko, additional, Powrie, Fiona, additional, Pugh, Chris, additional, Quek, Lynn, additional, Robbins, Peter A, additional, Robson, Kathryn, additional, Russo, Alexandra, additional, Sahgal, Natasha, additional, van Schouwenburg, Pauline A, additional, Schuh, Anna, additional, Silverman, Earl, additional, Simmons, Alison, additional, Sørensen, Per Soelberg, additional, Sweeney, Elizabeth, additional, Taylor, John, additional, Thakker, Rajesh V, additional, Tomlinson, Ian, additional, Trebes, Amy, additional, Twigg, Stephen R F, additional, Uhlig, Holm H, additional, Vyas, Paresh, additional, Vyse, Tim, additional, Wall, Steven A, additional, Watkins, Hugh, additional, Whyte, Michael P, additional, Witty, Lorna, additional, Wright, Ben, additional, Yau, Chris, additional, Buck, David, additional, Humphray, Sean, additional, Ratcliffe, Peter J, additional, Bell, John I, additional, Wilkie, Andrew O M, additional, Bentley, David, additional, Donnelly, Peter, additional, and McVean, Gilean, additional

Published
2015
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35. Functional Analysis of the Anti-adalimumab Response Using Patient-derived Monoclonal Antibodies

Author

van Schouwenburg, Pauline A., primary, Kruithof, Simone, additional, Votsmeier, Christian, additional, van Schie, Karin, additional, Hart, Margreet H., additional, de Jong, Rob N., additional, van Buren, Esther E.L., additional, van Ham, Marieke, additional, Aarden, Lucien, additional, Wolbink, Gertjan, additional, Wouters, Diana, additional, and Rispens, Theo, additional

Published
2014
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37. Evaluation of the Antigen-Experienced B-Cell Receptor Repertoire in Healthy Children and Adults.

Author

Jspeert, Hanna I., van Schouwenburg, Pauline A., van Zessen, David, Pico-Knijnenburg, Ingrid, Driessen, Gertjan J., Stubbs, Andrew P., van der Burg, Mirjam, Jacobs, Heinz, Casali, Paolo, and Rosenberg, Alex

Subjects
IMMUNE recognition, SOMATIC mutation, B cell receptors
Abstract

Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens. Insights into the processes of SHM, selection, and CSR can be obtained by studying the antigen-experienced BR repertoire. Currently, a large reference data set of healthy children and adults, which ranges from neonates to the elderly, is not available. In this study, we analyzed the antigen-experienced repertoire of 38 healthy donors (HD), ranging from cord blood to 74 years old, by sequencing IGA and IGG transcripts using next generation sequencing. This resulted in a large, freely available reference data set containing 412,890 IGA and IGG transcripts. We used this data set to study mutation levels, SHM patterns, antigenic selection, and CSR from birth to elderly HD. Only small differences were observed in SHM patterns, while the mutation levels increase in early childhood and stabilize at 6 years of age at around 7%. Furthermore, comparison of the antigen-experienced repertoire with sequences from the naive immune repertoire showed that features associated with autoimmunity such as long CDR3 length and IGHV4-34 usage are reduced in the antigen-experienced repertoire. Moreover, IGA2 and IGG2 usage was increased in HD in higher age categories, while IGG1 usage was decreased. In addition, we studied clonal relationship in the different samples. Clonally related sequences were found with different subclasses. Interestingly, we found transcripts with the same CDR1-CDR3 sequence, but different subclasses. Together, these data suggest that a single antigen can provoke a B-cell response with BR of different subclasses and that, during the course of an immune response, some B cells change their isotype without acquiring additional SHM or can directly switch to different isotypes. [ABSTRACT FROM AUTHOR]

Published
2016
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38. Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation

Author

van Schouwenburg, Pauline A, primary, van de Stadt, Lotte A, additional, de Jong, Rob N, additional, van Buren, Esther E L, additional, Kruithof, Simone, additional, de Groot, Els, additional, Hart, Margreet, additional, van Ham, S Marieke, additional, Rispens, Theo, additional, Aarden, Lucien, additional, Wolbink, Gerrit Jan, additional, and Wouters, Diana, additional

Published
2012
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41. NGS-Based B-Cell Receptor Repertoire AnalysisRepertoire analyses in the Context of Inborn Errors of Immunity.

Author

van Schouwenburg PA, van der Burg M, and IJspeert H

Subjects
Autoimmunity, Humans, Phenotype, Receptors, Antigen, B-Cell genetics, Immune System, Immunoglobulin Class Switching
Abstract

Inborn errors of immunity (IEI) are genetic defects that can affect both the innate and the adaptive immune system. Patients with IEI usually present with recurrent infections, but many also suffer from immune dysregulation, autoimmunity, and malignancies.Inborn errors of the immune system can cause defects in the development and selection of the B-cell receptor (BCR ) repertoire. Patients with IEI can have a defect in one of the key processes of immune repertoire formation like V(D)J recombination, somatic hypermutation (SHM), class switch recombination (CSR), or (pre-)BCR signalling and proliferation. However, also other genetic defects can lead to quantitative and qualitative differences in the immune repertoire.In this chapter, we will give an overview of protocols that can be used to study the immune repertoire in patients with IEI, provide considerations to take into account before setting up experiments, and discuss analysis of the immune repertoire data using Antigen Receptor Galaxy (ARGalaxy)., (© 2022. The Author(s).)

Published
2022
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