NFKB2 Mutation in a Patient with Lymphopenia and Extreme Cold Sensitivity (a case report)
Abstract
NF-κB pathway is a complex protein playing an important role in regulating lymphocyte development, immune responses, inflammation, cell proliferation, and cell death. The NF-kB signaling pathway has been described to be associated with canonical and noncanonical pathway. The canonical pathway utilizes NF-kB1, whereas the latter pathway involves NF-kB2, which is the cornerstone of the non-canonical NF-kB pathway, and has been shown to be critical for the development of secondary lymphoid organs, B cell development, and the humoral response to T-dependent and T-independent antigens. In this study, we investigated the patient with chief complain of low body temperature as well as feeling cold even in the warm seasons since 15 years ago. We reported a middle age man with mild lymphopenia and no significant infection, but hypothermia with significant chills even in the warm seasons with a mutation in NF-κB2 pathway.
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15. Aird A, Lagos M, Vargas-Hernandez A, Posey JE, Coban-Akdemir Z, Jhangiani S, et al. Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome. Frontiers in pediatrics. 2019;7:303.
16. Nasomyont N, Lindsley AW, Assa'ad A, Dawson DB, Neilson DE, Brady CC, et al. Central diabetes insipidus in a patient with NFKB2 mutation: Expanding the endocrine phenotype in DAVID syndrome. The Journal of clinical endocrinology and metabolism. 2019.
17. Kotlinowski J, Bukowska-Strakova K, Koppolu A, Kosinska J, Pydyn N, Stawinski P, et al. A Novel Monoallelic Nonsense Mutation in the NFKB2 Gene Does Not Cause a Clinical Manifestation. Frontiers in genetics. 2019;10:140.
18. Chen K, Coonrod EM, Kumanovics A, Franks ZF, Durtschi JD, Margraf RL, et al. Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet. 2013;93(5):812-24.
19. Okamura K, Uchida T, Hayashi M, Yaguchi Y, Hemmi A, Murata I, et al. Neutrophilic dermatosisassociated with an NFKB2 mutation. Clinical and experimental dermatology. 2019;44(3):350-2.
20. Kaustio M, Haapaniemi E, Göös H, Hautala T, Park G, Syrjänen J, et al. Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. Journal of Allergy and Clinical Immunology. 2017;140(3):782-96.
2. Hoesel B, Schmid JA. The complexity of NFkappaB signaling in inflammation and cancer. Molecular cancer. 2013;12:86.
3. Sun SC, Ley SC. New insights into NF-kappaB regulation and function. Trends in immunology. 2008;29(10):469-78.
4. Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annual review of immunology. 2009;27:693-733.
5. Hayden MS, Ghosh S. Shared principles in NFkappaB signaling. Cell. 2008;132(3):344-62.
6. Yang HT, Papoutsopoulou S, Belich M, Brender C, Janzen J, Gantke T, et al. Coordinate regulationof TPL-2 and NF-kappaB signaling in macrophages by NF-kappaB1 p105. Molecular and cellular biology. 2012;32(17):3438-51.
7. Sun SC. The noncanonical NF-kappaB pathway. Immunological reviews. 2012;246(1):125-40.
8. Nijenhuis T, Klasen I, Weemaes C, Preijers F, De Vries E, Van der Meer J. Common variable immunodeficiency (CVID) in a family: an autosomal dominant mode of inheritance. The Netherlands journal of medicine. 2001;59(3):134-9.
9. Klemann C, Camacho-Ordonez N, Yang L, Eskandarian Z, Rojas-Restrepo JL, Frede N, et al. Clinical and Immunological Phenotype of Patients With Primary Immunodeficiency Due to Damaging Mutations in NFKB2. Frontiers in immunology. 2019;10:297.
10. Quentien MH, Delemer B, Papadimitriou DT, Souchon PF, Jaussaud R, Pagnier A, et al. Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections. The Journal of clinical endocrinology and metabolism. 2012;97(1):E121-8.
11. Liu Y, Hanson S, Gurugama P, Jones A, Clark B, Ibrahim MA. Novel NFKB2 mutation in earlyonset CVID. Journal of clinical immunology. 2014;34(6):686-90.
12. Lougaris V, Tabellini G, Vitali M, Baronio M, Patrizi O, Tampella G, et al. Defective natural killercell cytotoxic activity in NFKB2-mutated CVIDlike disease. The Journal of allergy and clinical immunology. 2015;135(6):1641-3.
13. Lee W-I, Huang J-L, Yeh K-W, Yang M-J, Lai M-C, Chen L-C, et al. Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype. The Pediatric infectious disease journal. 2013;32(9):1010-6.
14. Kuehn HS, Niemela JE, Sreedhara K, Stoddard JL, Grossman J, Wysocki CA, et al. Novel nonsense gain-of-function NFKB2 mutations associated with a combined immunodeficiency phenotype. Blood. 2017;130(13):1553-64.
15. Aird A, Lagos M, Vargas-Hernandez A, Posey JE, Coban-Akdemir Z, Jhangiani S, et al. Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome. Frontiers in pediatrics. 2019;7:303.
16. Nasomyont N, Lindsley AW, Assa'ad A, Dawson DB, Neilson DE, Brady CC, et al. Central diabetes insipidus in a patient with NFKB2 mutation: Expanding the endocrine phenotype in DAVID syndrome. The Journal of clinical endocrinology and metabolism. 2019.
17. Kotlinowski J, Bukowska-Strakova K, Koppolu A, Kosinska J, Pydyn N, Stawinski P, et al. A Novel Monoallelic Nonsense Mutation in the NFKB2 Gene Does Not Cause a Clinical Manifestation. Frontiers in genetics. 2019;10:140.
18. Chen K, Coonrod EM, Kumanovics A, Franks ZF, Durtschi JD, Margraf RL, et al. Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet. 2013;93(5):812-24.
19. Okamura K, Uchida T, Hayashi M, Yaguchi Y, Hemmi A, Murata I, et al. Neutrophilic dermatosisassociated with an NFKB2 mutation. Clinical and experimental dermatology. 2019;44(3):350-2.
20. Kaustio M, Haapaniemi E, Göös H, Hautala T, Park G, Syrjänen J, et al. Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. Journal of Allergy and Clinical Immunology. 2017;140(3):782-96.
| Files | ||
| Issue | Vol 2, No 4 (2019) | |
| Section | Case Report | |
| DOI | https://doi.org/10.22034/igj.2019.212824.1029 | |
| Keywords | ||
| Mutation NFKB2 Lymphopenia Chills | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rezaei A, Shirmast P, Eslamian MH. NFKB2 Mutation in a Patient with Lymphopenia and Extreme Cold Sensitivity (a case report). Immunol Genet J. 2019;2(4):207-212.
