1887

Abstract

Introduction. LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems.

Case Presentation. Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement. The patients partially responded to immunosuppressive therapies. A homozygous c.2496C>A, p.Cys832Ter (p.C832*) mutation in the LRBA gene causing a premature stop codon was detected. After molecular diagnosis, abatacept, as a target-specific molecule, was used with promising results.

Conclusion. LRBA deficiency is a recently defined defect, with variable presentations in different patients; a single, definitive treatment option is thus not yet available.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2018-10-15
2024-03-29
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References

  1. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol 2018; 38:96–128 [View Article][PubMed]
    [Google Scholar]
  2. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012; 90:986–1001 [View Article][PubMed]
    [Google Scholar]
  3. Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS 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; 130:481–488 [View Article][PubMed]
    [Google Scholar]
  4. Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P et al. Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: a longitudinal study. Pediatr Allergy Immunol 2017; 28:478–484 [View Article][PubMed]
    [Google Scholar]
  5. Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol 2016; 137:223–230 [View Article][PubMed]
    [Google Scholar]
  6. Kostel Bal S, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C et al. Multiple presentations of lrba deficiency: a single-center experience. J Clin Immunol 2017; 37:790–800 [View Article][PubMed]
    [Google Scholar]
  7. Sansom DM. IMMUNOLOGY. Moving CTLA-4 from the trash to recycling. Science 2015; 349:377–378 [View Article][PubMed]
    [Google Scholar]
  8. Lo B, Zhang K, Lu W, Zheng L, Zhang Q et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015; 349:436–440 [View Article][PubMed]
    [Google Scholar]
  9. Lo B, Abdel-Motal UM. Lessons from CTLA-4 deficiency and checkpoint inhibition. Curr Opin Immunol 2017; 49:14–19 [View Article][PubMed]
    [Google Scholar]
  10. Barzaghi F, Passerini L, Bacchetta R. Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front Immunol 2012; 3:211 [View Article][PubMed]
    [Google Scholar]
  11. Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 2000; 106:R75–R81 [View Article][PubMed]
    [Google Scholar]
  12. Zama D, Cocchi I, Masetti R, Specchia F, Alvisi P et al. Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (IPEX) with intractable diarrhea. Ital J Pediatr 2014; 40:68 [View Article][PubMed]
    [Google Scholar]
  13. Sheikine Y, Woda CB, Lee PY, Chatila TA, Keles S et al. Renal involvement in the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder. Pediatr Nephrol 2015; 30:1197–1202 [View Article][PubMed]
    [Google Scholar]
  14. Barzaghi F, Passerini L, Gambineri E, Ciullini Mannurita S, Cornu T et al. Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome. J Autoimmun 2012; 38:49–58 [View Article][PubMed]
    [Google Scholar]
  15. Verbsky JW, Chatila TA. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders: an evolving web of heritable autoimmune diseases. Curr Opin Pediatr 2013; 25:708–714 [View Article][PubMed]
    [Google Scholar]
  16. Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 2006; 116:1713–1722 [View Article][PubMed]
    [Google Scholar]
  17. D'Hennezel E, Ben-Shoshan M, Ochs HD, Torgerson TR, Russell LJ et al. FOXP3 forkhead domain mutation and regulatory T cells in the IPEX syndrome. N Engl J Med 2009; 361:1710–1713 [View Article][PubMed]
    [Google Scholar]
  18. Moes N, Rieux-Laucat F, Begue B, Verdier J, Neven B et al. Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathy. Gastroenterology 2010; 139:770–778 [View Article][PubMed]
    [Google Scholar]
  19. Charbonnier LM, Janssen E, Chou J, Ohsumi TK, Keles S 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; 135:217–227 [View Article][PubMed]
    [Google Scholar]
  20. Saifi M, Wysocki CA. Autoimmune disease in primary immunodeficiency: at the crossroads of anti-infective immunity and self-tolerance. Immunol Allergy Clin North Am 2015; 35:731–752 [View Article][PubMed]
    [Google Scholar]
  21. Park JH, Levinson AI. Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol 2010; 134:97–103 [View Article][PubMed]
    [Google Scholar]
  22. Rao N, Mackinnon AC, Routes JM. Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency-histologic and immunohistochemical analyses of 16 cases. Hum Pathol 2015; 46:1306–1314 [View Article][PubMed]
    [Google Scholar]
  23. Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S et al. British lung foundation/united kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 2017; 5:938–945 [View Article][PubMed]
    [Google Scholar]
  24. Seidel MG, Böhm K, Dogu F, Worth A, Thrasher A et al. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol 2018; 141:770–775 [View Article][PubMed]
    [Google Scholar]
  25. Aksu G, Genel F, Koturoğlu G, Kurugöl Z, Kütükçüler N. Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr 2006; 48:19–24[PubMed]
    [Google Scholar]
  26. Azarsiz E, Karaca NE, Aksu G, Kutukculer N. Reference values for B-cell surface markers and co-receptors associated with primary immune deficiencies in healthy Turkish children. Int J Immunopathol Pharmacol 2017; 30:194–200 [View Article][PubMed]
    [Google Scholar]
  27. Martins TB, Bandhauer ME, Bunker AM, Roberts WL, Hill HR. New childhood and adult reference intervals for total IgE. J Allergy Clin Immunol 2014; 133:589–591 [View Article][PubMed]
    [Google Scholar]
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