Still’s disease in a patient with common variable immunodeficiency: NFKB1 defect

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Сommon variable immunodeficiency is the most prevalent form of inborn errors of immunity, however, genetic cause may be identified in less than a third of the cases. Pathogenic variants in the subunit 1 of nuclear factor κB are thought to be one of the most frequent monogenic causes of common variable immunodeficiency. Besides the humoral immunodeficiency, NFKB1 defect is characterized by a wide range of autoimmune, autoinflammatory and hematological features. To date, there are no standardized guidelines for immunosuppressive or anti-inflammatory therapy in patients with NFKB1 deficiency.

We report on a 62 year old woman with common variable immunodeficiency due to heterozygous mutation in the NFKB1 gene, complicated by a systemic form of Still’s disease. Since initiation of the anti-cytokine therapy with the interleukin 6 antagonist olokizumab, resolution of constitutional symptoms has been achieved. Over the 1.5-years follow-up there has been an improvement on lymphadenopathy and joint syndrome according to computed tomography scan and ultrasound.

Variety of manifestations of immune disregulation in complex of symptoms of NFKB1 defect forces a neccessity of awareness of the specialists and requires a multidisciplinary approach to selection of an optimal tactic to patient treatment.

About the authors

Anna A. Roppelt

Moscow City Clinical Hospital 52

Author for correspondence.
Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-5132-1267
SPIN-code: 7249-4423

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Еkaterina A. Nikitaeva

I.M. Sechenov First Moscow State Medical University (Sechenovskiy University)

Email: katenikitaev@gmail.com
ORCID iD: 0009-0005-3090-8487
SPIN-code: 7214-7243
Russian Federation, Moscow

Gerelma V. Andrenova

Moscow City Clinical Hospital 52

Email: andrenovagv@gmail.com
ORCID iD: 0000-0001-7053-3900
SPIN-code: 2891-1650
Russian Federation, Moscow

Ulyana A. Markina

Moscow City Clinical Hospital 52

Email: itcher.md@bk.ru
ORCID iD: 0000-0002-6646-4233
SPIN-code: 6424-0012

MD

Russian Federation, Moscow

Tatyana S. Kruglova

Moscow City Clinical Hospital 52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-4949-9178
SPIN-code: 2884-5000

Cand. Sci. (Medicine)

Russian Federation, Moscow

Elena A. Baryakh

Moscow City Clinical Hospital 52

Email: ebaryakh@gmail.com
ORCID iD: 0000-0001-6880-9269
SPIN-code: 5280-7513

Dr. Sci. (Medicine)

Russian Federation, Moscow

Zinaida Yu. Mutovina

Moscow City Clinical Hospital 52; Central State Medical Academy

Email: zmutovina@mail.ru
ORCID iD: 0000-0001-5809-6015
SPIN-code: 3943-7930

Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow

Rinat R. Mudarisov

Moscow City Clinical Hospital 52

Email: MudarisovRR1@zdrav.mos.ru
ORCID iD: 0000-0001-8890-4669
SPIN-code: 4550-8145

Cand. Sci. (Medicine)

Russian Federation, Moscow

Alexander V. Karaulov

I.M. Sechenov First Moscow State Medical University (Sechenovskiy University); Life Improvement by Future Technologies (LIFT) Center

Email: drkaraulov@mail.ru
ORCID iD: 0000-0002-1930-5424
SPIN-code: 4122-5565

MD, Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow

Maryana A. Lysenko

Moscow City Clinical Hospital 52; The Russian National Research Medical University named after N.I. Pirogov

Email: gkb52@zdrav.mos.ru
ORCID iD: 0000-0001-6010-7975
SPIN-code: 3887-6250

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; Moscow

Darya S. Fomina

Moscow City Clinical Hospital 52; I.M. Sechenov First Moscow State Medical University (Sechenovskiy University); Astana Medical University

Email: daria_fomina@mail.ru
ORCID iD: 0000-0002-5083-6637
SPIN-code: 3023-4538

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow; Astana, Kazakhstan

References

  1. Odnoletkova I, Kindle G, Quinti I, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201. doi: 10.1186/s13023-018-0941-0 EDN: TVJSCJ
  2. Maffucci P, Filion CA, Boisson B, et al. Genetic diagnosis using whole exome sequencing in common variable immunodeficiency. Front Immunol. 2016;7:220. doi: 10.3389/fimmu.2016.00220
  3. Rojas-Restrepo J, Caballero-Oteyza A, Huebscher K, et al. Establishing the molecular diagnoses in a cohort of 291 patients with predominantly antibody deficiency by targeted next-generation sequencing: experience from a monocentric study. Front Immunol. 2021;12:786516. doi: 10.3389/fimmu.2021.786516 EDN: CBEGQR
  4. Tuijnenburg P, Lango Allen H, Burns SO, et al. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans. J Allergy Clin Immunol. 2018;142(4):1285–1296. doi: 10.1016/j.jaci.2018.01.039 EDN: VGFACK
  5. Cunningham-Rundles C, Casanova JL, Boisson B. Genetics and clinical phenotypes in common variable immunodeficiency. Front Genet. 2024;14:1272912. doi: 10.3389/fgene.2023.1272912 EDN: RLQTCL
  6. Ramirez NJ, Posadas-Cantera S, Caballero-Oteyza A, et al. There is no gene for CVID — novel monogenetic causes for primary antibody deficiency. Curr Opin Immunol. 2021;72:176–185. doi: 10.1016/j.coi.2021.05.010 EDN: PCNXCS
  7. Guo Q, Jin Y, Chen X, et al. NF-κB in biology and targeted therapy: new insights and translational implications. Signal Transduct Target Ther. 2024;9(1):53. doi: 10.1038/s41392-024-01757-9 EDN: DWDQMY
  8. Hayden MS, Ghosh S. NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 2012;26(3):203–234. doi: 10.1101/gad.183434.111
  9. Hoeger B, Serwas NK, Boztug K. Human NF-κB1 haploinsufficiency and Epstein–Barr virus-induced disease-molecular mechanisms and consequences. Front Immunol. 2018;8:1978. doi: 10.3389/fimmu.2017.01978
  10. Klemann C, Camacho-Ordonez N, Yang L, et al. Clinical and immunological phenotype of patients with primary immunodeficiency due to damaging mutations in NFKB2. Front Immunol. 2019;10:297. doi: 10.3389/fimmu.2019.00297 EDN: EFTNBP
  11. Chen K, Coonrod EM, Kumánovics A, et al. Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet. 2013;93(5):812–824. doi: 10.1016/j.ajhg.2013.09.009
  12. Lorenzini T, Fliegauf M, Klammer N, et al. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations. J Allergy Clin Immunol. 2021;148(5):1345. doi: 10.1016/j.jaci.2021.09.001 EDN: WYDHAN
  13. Schröder C, Sogkas G, Fliegauf M, et al. Late-onset antibody deficiency due to monoallelic alterations in NFKB1. Front Immunol. 2019;10:2618. doi: 10.3389/fimmu.2019.02618
  14. Kaustio M, Haapaniemi E, Göös H, et al. Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. J Allergy Clin Immunol. 2021;148(6):1603. doi: 10.1016/j.jaci.2021.09.012
  15. Kilic B, Ozturk A, Karup S, et al. Efficacy and safety of biologic drugs in Still’s disease: a systematic review and network meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2025;64(1):22–31. doi: 10.1093/rheumatology/keae295 EDN: SMVEGA
  16. Fliegauf M, Grimbacher B. Nuclear factor κB mutations in human subjects: the devil is in the details. J Allergy Clin Immunol. 2018;142(4):1062–1065. doi: 10.1016/j.jaci.2018.06.050
  17. Tuovinen EA, Kuismin O, Soikkonen L, et al. Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae. Clin Immunol. 2023;246:109181. doi: 10.1016/j.clim.2022.109181 EDN: HTQNRD
  18. Fliegauf M, Bryant VL, Frede N, et al. Haploinsufficiency of the NF-κB1 Subunit p50 in common variable immunodeficiency. Am J Hum Genet. 2015;97(3):389–403. doi: 10.1016/j.ajhg.2015.07.008 EDN: VFSZHD

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 ABV-press

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).