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Journal of Clinical Immunology

, Volume 38, Issue 4, pp 471–474 | Cite as

Novel LRBA Mutation and Possible Germinal Mosaicism in a Slavic Family

  • Svetlana O. SharapovaEmail author
  • Emma Haapaniemi
  • Inga S. Sakovich
  • Jessica Rojas
  • Laura Gámez-Díaz
  • Yuliya E. Mareika
  • Irina E. Guryanova
  • Alexandr A. Migas
  • Taisiya M. Mikhaleuskaya
  • Bodo Grimbacher
  • Olga V. Aleinikova
Letter to Editor

To the Editor,

Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency was first described in 2012 [1]. Currently, the data more than 100 patients around the world has been published, presenting with a broad range of clinical, immunologic, and genetic manifestations [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22]. This immunodeficiency can manifest as common variable immunodeficiency (CVID), autoimmune lymphoproliferative-like syndrome (ALPS)-like, immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX)-like, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)-like, isolated diabetes mellitus, arthritis, and combined immunodeficiency (CID) with multiple autoimmune diseases [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22].

Here, we report the clinical, genetic, and immunological data from two siblings in a Belarusian family with a homozygous, truncating LRBAmutation...

Keywords

LRBA homozygous mutation multiple autoimmunity germline mosaicism Slavic family 

Notes

Acknowledgments

We sincerely thank all our patients and their family members for their trust, cooperation, and consent to perform genetic and functional assays and the referring doctors for their help. We are also grateful to doctor Polina Stepensky and Professor Markus Seidel for the consultation on our Pt2.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

10875_2018_515_MOESM1_ESM.docx (119 kb)
ESM 1 (DOCX 119 kb)

References

  1. 1.
    Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90:986–1001.Google Scholar
  2. 2.
    Burns SO, Zenner HL, Plagnol V, Curtis J, Mok K, Eisenhut M, et al. LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. J Allergy Clin Immunol. 2012;130(6):1428–32.Google Scholar
  3. 3.
    Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, et al. Clinical, immunological, molecular analyses and outcomes of Iranian patients with LRBA deficiency: a longitudinal study. Pediatr Allergy Immunol. 2017;28(5):478–84.Google Scholar
  4. 4.
    Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of phenotypes associated with mutations in LRBA. J Clin Immunol. 2016;36(1):33–45.Google Scholar
  5. 5.
    Seidel MG, Böhm K, Dogu F, Worth A, Thrasher A, Florkin B, et al. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2017;141:770–775.e1.  https://doi.org/10.1016/j.jaci.2017.04.023.
  6. 6.
    Kostel Bal S, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple presentations of LRBA deficiency: a single-center experience. J Clin Immunol. 2017;37:790–800.  https://doi.org/10.1007/s10875-017-0446-y.
  7. 7.
    Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223–30.Google Scholar
  8. 8.
    Charbonnier LM, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, et al. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol. 2015;135(1):217–27.Google Scholar
  9. 9.
    Johnson MB, De Franco E, Lango Allen H, Al Senani A, Elbarbary N, Siklar Z, et al. Recessively inherited LRBA mutations cause autoimmunity presenting as neonatal diabetes. Diabetes. 2017;66(8):2316–22.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015;349(6246):436–40.CrossRefPubMedGoogle Scholar
  11. 11.
    Schreiner F, Plamper M, Dueker G, Schoenberger S, Gámez-Díaz L, Grimbacher B, et al. Infancy-onset T1DM, short stature, and severe immunodysregulation in two siblings with a homozygous LRBA mutation. J Clin Endocrinol Metab. 2016;101(3):898–904.Google Scholar
  12. 12.
    Bratanič N, Kovač J, Pohar K, Trebušak Podkrajšek K, Ihan A, Battelino T, et al. Multifocal gastric adenocarcinoma in a patient with LRBA deficiency. Orphanet J Rare Dis. 2017;12(1):131.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Al Sukaiti N, Abdel Rahman K, Al Shekaili J, Al Oraimi S, Al Sinani A, Al Rahbi N, et al. Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation. Clin Transl Immunology. 2017;6(5):e144.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Alroqi FJ, Charbonnier LM, Baris S, Kiykim A, Chou J, Platt CD, et al. Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation. J Allergy Clin Immunol. 2017;141:1050–1059.e10.  https://doi.org/10.1016/j.jaci.2017.05.022.
  15. 15.
    Sari S, Dogu F, Hwa V, Haskologlu S, Dauber A, Rosenfeld R, et al. A successful HSCT in a girl with novel LRBA mutation with refractory celiac disease. J Clin Immunol. 2016;36(1):8–11.Google Scholar
  16. 16.
    Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol. 2012;130(2):481–8.Google Scholar
  17. 17.
    Bakhtiar S, Ruemmele F, Charbit-Henrion F, Lévy E, Rieux-Laucat F, Cerf-Bensussan N, et al. Atypical manifestation of LPS-responsive beige-like anchor deficiency syndrome as an autoimmune endocrine disorder without enteropathy and immunodeficiency. Front Pediatr. 2016;4:98.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Seidel MG, Hirschmugl T, Gamez-Diaz L, Schwinger W, Serwas N, Deutschmann A, et al. Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency. J Allergy Clin Immunol. 2015;135(5):1384–90.Google Scholar
  19. 19.
    Tesi B, Priftakis P, Lindgren F, Chiang SC, Kartalis N, Löfstedt A, et al. Successful hematopoietic stem cell transplantation in a patient with LPS-responsive beige-like anchor (LRBA) gene mutation. J Clin Immunol. 2016;36(5):480–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Levy E, Stolzenberg MC, Bruneau J, Breton S, Neven B, Sauvion S, et al. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis. Clin Immunol. 2016;168:88–93.CrossRefPubMedGoogle Scholar
  21. 21.
    Revel-Vilk S, Fischer U, Keller B, Nabhani S, Gámez-Díaz L, Rensing-Ehl A, et al. Autoimmune lymphoproliferative syndrome-like disease in patients with LRBA mutation. Clin Immunol. 2015;159(1):84–92.Google Scholar
  22. 22.
    Besnard C, Levy E, Aladjidi N, Stolzenberg MC, Magerus-Chatinet A, Alibeu O, et al. Pediatric-onset Evans syndrome: heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations. Clin Immunol. 2018;188:52–7.Google Scholar
  23. 23.
    Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, et al. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet. 2015;47(7):692–5.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Anazi S, Al-Sabban E, Alkuraya FS. Gonadal mosaicism as a rare cause of autosomal recessive inheritance. Clin Genet. 2014;85(3):278–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110d result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15:88–97.CrossRefPubMedGoogle Scholar
  26. 26.
    Segundo GRS, Takano OA, Moraes LSL, Nadaf MISV, Fernandes SJ, Ochs HD, et al. Paternal gonadal mosaicism as cause of a puzzling inheritance pattern of activated PI3-kinase delta syndrome. Ann Allergy Asthma Immunol. 2017;119(6):564–6.Google Scholar
  27. 27.
    Maglione PJ, Overbey JR, Cunningham-Rundles C. Progression of common variable immunodeficiency interstitial lung disease accompanies distinct pulmonary and laboratory findings. J Allergy Clin Immunol Pract. 2015;3(6):941–50.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Haapaniemi EM, Kaustio M, Rajala HL, van Adrichem AJ, Kainulainen L, Glumoff V, et al. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood. 2015;125(4):639–48.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Svetlana O. Sharapova
    • 1
    Email author
  • Emma Haapaniemi
    • 2
    • 3
  • Inga S. Sakovich
    • 1
  • Jessica Rojas
    • 4
  • Laura Gámez-Díaz
    • 4
  • Yuliya E. Mareika
    • 1
  • Irina E. Guryanova
    • 1
  • Alexandr A. Migas
    • 1
  • Taisiya M. Mikhaleuskaya
    • 1
  • Bodo Grimbacher
    • 4
  • Olga V. Aleinikova
    • 1
  1. 1.Research Department, Immunology Laboratory, Belarusian Research Center for Pediatric Oncology, Hematology and ImmunologyBorovlianiBelarus
  2. 2.Department of Hematology and Regenerative Medicine, Karolinska InstitutetHuddingeSweden
  3. 3.Genome-Scale Biology ProgramUniversity of HelsinkiHelsinkiFinland
  4. 4.Center for Chronic Immunodeficiency, Medical CenterUniversity of FreiburgFreiburg im BreisgauGermany

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