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ResearchIn-Press PreviewImmunologyInflammation Open Access | 10.1172/jci.insight.200002

Truncating RELA variants drive autoinflammation and autoimmunity by impairing the negative feedback control of NF-κB

Nadja Lucas,1 Sophia Weidler,1 Antonia A. Eicher,2 Baerbel Keller,3 Özlem Satirer,4 Adam Desrochers,1 Timothy J.S. Ramnarine,2 Mohammad Mokhtari,2 Sophie Elstner,1 Timmy Strauss,1 Simon W. Mages,2 Arek Kendirli,5 Oana Cristina Buzoianu,4 Tobias B. Haack,6 Lina Igel,7 Tim Niehues,7 Sandra von Hardenberg,8 Maria Fasshauer,9 Rami Abou Jamra,10 Hagen Ott,11 Ulrike Hüffmeier,12 Catharina Schütz,1 Marisa Bijwaard,1 Susan Wagner,1 Paulina Switala,1 Sarah Koss,1 Jurek Schultz,13 Stefanie Kretschmer,1 Jasmin Kümmerle-Deschner,4 Christine Wolf,1 Johanna Klughammer,2 and Min Ae Lee-Kirsch1

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Find articles by Lucas, N. in: PubMed | Google Scholar

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Find articles by Satirer, Ö. in: PubMed | Google Scholar

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Find articles by Buzoianu, O. in: PubMed | Google Scholar

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Find articles by von Hardenberg, S. in: PubMed | Google Scholar

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Find articles by Abou Jamra, R. in: PubMed | Google Scholar

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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

1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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1Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

3Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany

4Division of Paediatric Rheumatology and Autoinflammation Reference Centre T, University Hospital Tübingen, Tübingen, Germany

5Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

6Institute of Human Genetics, University Hospital Tübingen, Tübingen, Germany

7Department of Pediatrics, Helios Klinik Krefeld, Krefeld, Germany

8Department of Human Genetics, Hannover Medical School, Hannover, Germany

9Hospital for Children and Adolescents, Hospital St. Georg, Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany

10Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

11Section of Pediatric Dermatology, Munich University Center for Children with Medical and Developmental Complexity, Munich, Germany

12Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

13Department of Pediatric Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Published August 11, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.200002.
Copyright © 2026, Lucas et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 11, 2026 - Version history
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Abstract

The NF-κB signaling pathway coordinates inflammation, cell survival, and proliferation, while restraining excessive cell death to maintain immune homeostasis. Truncating mutations in RELA, encoding the NF-κB subunit p65, have been linked to autoinflammation and autoimmunity, but the underlying mechanisms remain incompletely defined. We investigated six patients from five unrelated families carrying previously unreported heterozygous truncating RELA variants. Despite reduced p65 expression, patients exhibited a broad spectrum of inflammatory manifestations alongside elevated baseline and stimulus-induced pro-inflammatory cytokines. Functional analyses in patient-derived cells and mutant RELA knock-in models showed that upstream NF-κB signaling was intact, but induction of inhibitory regulators such as IκBα and A20 was impaired. This defective feedback control shifted immune homeostasis toward amplified inflammatory responses that depended on the residual activity of the remaining functional RELA allele. Single-cell transcriptomics revealed distinct cell type-specific consequences: monocytes displayed constitutive type I interferon and NF-κB activation, B cells retained partial compensatory signaling, whereas T and NK cells exhibited transcriptional signatures of cell death pathways. Patient fibroblasts and mutant RELA knock-in cells further confirmed enhanced TNF-induced inflammatory gene expression and hypersensitivity to apoptosis and necroptosis. These findings establish RELA haploinsufficiency as a cause of systemic immune dysregulation, and link defective NF-κB feedback control to unchecked inflammation and inflammatory cell death.

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