Advertisement

Corrigendum Free access | 10.1172/JCI91162

Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency

Jolan E. Walter, Lindsey B. Rosen, Krisztian Csomos, Jacob M. Rosenberg, Divij Mathew, Marton Keszei, Boglarka Ujhazi, Karin Chen, Yu Nee Lee, Irit Tirosh, Kerry Dobbs, Waleed Al-Herz, Morton J. Cowan, Jennifer Puck, Jack J. Bleesing, Michael S. Grimley, Harry Malech, Suk See De Ravin, Andrew R. Gennery, Roshini S. Abraham, Avni Y. Joshi, Thomas G. Boyce, Manish J. Butte, Kari C. Nadeau, Imelda Balboni, Kathleen E. Sullivan, Javeed Akhter, Mehdi Adeli, Reem A. El-Feky, Dalia H. El-Ghoneimy, Ghassan Dbaibo, Rima Wakim, Chiara Azzari, Paolo Palma, Caterina Cancrini, Kelly Capuder, Antonio Condino-Neto, Beatriz T. Costa-Carvalho, Joao Bosco Oliveira, Chaim Roifman, David Buchbinder, Attila Kumanovics, Jose Luis Franco, Tim Niehues, Catharina Schuetz, Taco Kuijpers, Christina Yee, Janet Chou, Michel J. Masaad, Raif Geha, Gulbu Uzel, Rebecca Gelman, Steven M. Holland, Mike Recher, Paul J. Utz, Sarah K. Browne, and Luigi D. Notarangelo

Find articles by Walter, J. in: JCI | PubMed | Google Scholar

Find articles by Rosen, L. in: JCI | PubMed | Google Scholar

Find articles by Csomos, K. in: JCI | PubMed | Google Scholar

Find articles by Rosenberg, J. in: JCI | PubMed | Google Scholar

Find articles by Mathew, D. in: JCI | PubMed | Google Scholar

Find articles by Keszei, M. in: JCI | PubMed | Google Scholar

Find articles by Ujhazi, B. in: JCI | PubMed | Google Scholar

Find articles by Chen, K. in: JCI | PubMed | Google Scholar

Find articles by Lee, Y. in: JCI | PubMed | Google Scholar

Find articles by Tirosh, I. in: JCI | PubMed | Google Scholar

Find articles by Dobbs, K. in: JCI | PubMed | Google Scholar

Find articles by Al-Herz, W. in: JCI | PubMed | Google Scholar

Find articles by Cowan, M. in: JCI | PubMed | Google Scholar

Find articles by Puck, J. in: JCI | PubMed | Google Scholar

Find articles by Bleesing, J. in: JCI | PubMed | Google Scholar

Find articles by Grimley, M. in: JCI | PubMed | Google Scholar

Find articles by Malech, H. in: JCI | PubMed | Google Scholar

Find articles by De Ravin, S. in: JCI | PubMed | Google Scholar

Find articles by Gennery, A. in: JCI | PubMed | Google Scholar

Find articles by Abraham, R. in: JCI | PubMed | Google Scholar

Find articles by Joshi, A. in: JCI | PubMed | Google Scholar

Find articles by Boyce, T. in: JCI | PubMed | Google Scholar

Find articles by Butte, M. in: JCI | PubMed | Google Scholar

Find articles by Nadeau, K. in: JCI | PubMed | Google Scholar

Find articles by Balboni, I. in: JCI | PubMed | Google Scholar

Find articles by Sullivan, K. in: JCI | PubMed | Google Scholar

Find articles by Akhter, J. in: JCI | PubMed | Google Scholar

Find articles by Adeli, M. in: JCI | PubMed | Google Scholar

Find articles by El-Feky, R. in: JCI | PubMed | Google Scholar

Find articles by El-Ghoneimy, D. in: JCI | PubMed | Google Scholar

Find articles by Dbaibo, G. in: JCI | PubMed | Google Scholar

Find articles by Wakim, R. in: JCI | PubMed | Google Scholar

Find articles by Azzari, C. in: JCI | PubMed | Google Scholar

Find articles by Palma, P. in: JCI | PubMed | Google Scholar

Find articles by Cancrini, C. in: JCI | PubMed | Google Scholar

Find articles by Capuder, K. in: JCI | PubMed | Google Scholar

Find articles by Condino-Neto, A. in: JCI | PubMed | Google Scholar

Find articles by Costa-Carvalho, B. in: JCI | PubMed | Google Scholar

Find articles by Oliveira, J. in: JCI | PubMed | Google Scholar

Find articles by Roifman, C. in: JCI | PubMed | Google Scholar

Find articles by Buchbinder, D. in: JCI | PubMed | Google Scholar

Find articles by Kumanovics, A. in: JCI | PubMed | Google Scholar

Find articles by Franco, J. in: JCI | PubMed | Google Scholar

Find articles by Niehues, T. in: JCI | PubMed | Google Scholar

Find articles by Schuetz, C. in: JCI | PubMed | Google Scholar

Find articles by Kuijpers, T. in: JCI | PubMed | Google Scholar

Find articles by Yee, C. in: JCI | PubMed | Google Scholar

Find articles by Chou, J. in: JCI | PubMed | Google Scholar

Find articles by Masaad, M. in: JCI | PubMed | Google Scholar

Find articles by Geha, R. in: JCI | PubMed | Google Scholar

Find articles by Uzel, G. in: JCI | PubMed | Google Scholar

Find articles by Gelman, R. in: JCI | PubMed | Google Scholar

Find articles by Holland, S. in: JCI | PubMed | Google Scholar

Find articles by Recher, M. in: JCI | PubMed | Google Scholar

Find articles by Utz, P. in: JCI | PubMed | Google Scholar

Find articles by Browne, S. in: JCI | PubMed | Google Scholar

Find articles by Notarangelo, L. in: JCI | PubMed | Google Scholar

Published November 1, 2016 - More info

Published in Volume 126, Issue 11 on November 1, 2016
J Clin Invest. 2016;126(11):4389–4389. https://doi.org/10.1172/JCI91162.
Copyright © 2016, American Society for Clinical Investigation
Published November 1, 2016 - Version history
View PDF

Related article:

Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency
Jolan E. Walter, … , Sarah K. Browne, Luigi D. Notarangelo
Jolan E. Walter, … , Sarah K. Browne, Luigi D. Notarangelo
Research Article Immunology Article has an altmetric score of 17

Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency

Abstract

Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti–IFN-α or anti–IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.

Authors

Jolan E. Walter, Lindsey B. Rosen, Krisztian Csomos, Jacob M. Rosenberg, Divij Mathew, Marton Keszei, Boglarka Ujhazi, Karin Chen, Yu Nee Lee, Irit Tirosh, Kerry Dobbs, Waleed Al-Herz, Morton J. Cowan, Jennifer Puck, Jack J. Bleesing, Michael S. Grimley, Harry Malech, Suk See De Ravin, Andrew R. Gennery, Roshini S. Abraham, Avni Y. Joshi, Thomas G. Boyce, Manish J. Butte, Kari C. Nadeau, Imelda Balboni, Kathleen E. Sullivan, Javeed Akhter, Mehdi Adeli, Reem A. El-Feky, Dalia H. El-Ghoneimy, Ghassan Dbaibo, Rima Wakim, Chiara Azzari, Paolo Palma, Caterina Cancrini, Kelly Capuder, Antonio Condino-Neto, Beatriz T. Costa-Carvalho, Joao Bosco Oliveira, Chaim Roifman, David Buchbinder, Attila Kumanovics, Jose Luis Franco, Tim Niehues, Catharina Schuetz, Taco Kuijpers, Christina Yee, Janet Chou, Michel J. Masaad, Raif Geha, Gulbu Uzel, Rebecca Gelman, Steven M. Holland, Mike Recher, Paul J. Utz, Sarah K. Browne, Luigi D. Notarangelo

×

Original citation: J Clin Invest. 2015;125(11):4135–4148. doi:10.1172/JCI80477.

Citation for this corrigendum: J Clin Invest. 2016;126(11):4389. doi:10.1172/JCI91162.

In the original version of Figure 2B, two of the patient identifiers were incorrectly noted. OS-11 and OS-12 were listed twice. The second instances should have been labeled as CID-11 and CID-12, respectively. The correct figure panel is below.

The authors regret the error.

Footnotes

See the related article beginning on page 4135.

Version history
  • Version 1 (November 1, 2016): Print issue publication
Advertisement
Advertisement