бородавки

WHIM-синдром: обзор литературы и описание двух собственных клинических наблюдений в одной семье

РЕДКИЕ ГЕМАТОЛОГИЧЕСКИЕ ЗАБОЛЕВАНИЯ И СИНДРОМЫ , , , ,

М.В. Марченко, Ю.Н. Кузнецов, А.В. Лапина, И.А. Михайлова, Т.А. Быкова, Т.С. Щеголева, В.В. Байков, А.Д. Кулагин

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Мария Викторовна Марченко, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; тел.: +7(812)338-62-65; e-mail: mv_bogomolova@mail.ru

Для цитирования: Марченко М.В., Кузнецов Ю.Н., Лапина А.В. и др. WHIM-синдром: обзор литературы и описание двух собственных клинических наблюдений в одной семье. Клиническая онкогематология. 2023;16(1):14–26.

DOI: 10.21320/2500-2139-2023-16-1-14-26

РЕФЕРАТ

WHIM-синдром (бородавки, гипогаммаглобулинемия, инфекции и миелокатексис) — редкое генетическое заболевание, связанное с активирующими герминальными мутациями в гене, кодирующем хемокиновый рецептор CXCR4. WHIM-синдром проявляется нейтропенией, лимфопенией, инфекциями и дегенеративными изменениями зрелых нейтрофилов с миелоидной гиперплазией костного мозга (миелокатексисом). У некоторых пациентов выявляются гипогаммаглобулинемия, персистирующие бородавки на коже, в области наружных половых органов, встречаются и другие локализации, а также наблюдаются врожденные пороки сердца. В настоящей работе проведен всесторонний анализ генетических основ, патофизиологии, клинической манифестации, диагностики и возможностей лечения WHIM-синдрома. Приводится описание двух собственных клинических наблюдений в одной семье.

Ключевые слова: WHIM-синдром, CXCR4, бородавки, гипогаммаглобулинемия, инфекции, миелокатексис.

Получено: 30 августа 2022 г.

Принято в печать: 2 декабря 2022 г.

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Статистика Plumx русский

ЛИТЕРАТУРА

  1. Wetzler M, Talpaz M, Kleinerman ES, et al. A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. Am J Med. 1990;89(5):663–72. doi: 10.1016/0002-9343(90)90187-i.
  2. Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet. 2003;34(1):70–4. doi: 10.1038/ng1149.
  3. Zuelzer WW. “Myelokathexis” – a new form of chronic granulocytopenia. Report of a case. N Engl J Med. 1964;270:699–704. doi: 10.1056/NEJM196404022701402.
  4. Krill CE, Smith HD, Mauer AM. Chronic idiopathic granulocytopenia. N Engl J Med. 1964;270:973–9. doi: 10.1056/NEJM196405072701902.
  5. Beaussant Cohen S, Fenneteau O, Plouvier E, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet J Rare Dis. 2012;7:71. doi: 10.1186/1750-1172-7-71.
  6. Heusinkveld LE, Majumdar S, Gao JL, et al. WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure. J Clin Immunol. 2019;39(6):532–56. doi: 10.1007/s10875-019-00665-w.
  7. McDermott DH, Murphy PM. WHIM syndrome: Immunopathogenesis, treatment and cure strategies. Immunol Rev. 2019;287(1):91–102. doi: 10.1111/imr.12719. PMID: 30565238.
  8. Bleul CC, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature. 1996;382(6594):829–33. doi: 10.1038/382829a0.
  9. Pozzobon T, Goldoni G, Viola A, Molon B. CXCR4 signaling in health and disease. Immunol Lett. 2016;177:6–15. doi: 10.1016/j.imlet.2016.06.006.
  10. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272(5263):872–7. doi: 10.1126/science.272.5263.872.
  11. Dar A, Goichberg P, Shinder V, et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat Immunol. 2005;6(10):1038–46. doi: 10.1038/ni1251.
  12. Kawai T, Choi U, Whiting-Theobald NL, et al. Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol. 2005;33(4):460–8. doi: 10.1016/j.exphem.2005.01.001.
  13. Balabanian K, Lagane B, Pablos JL, et al. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood. 2005;105(6):2449–57. doi: 10.1182/blood-2004-06-2289.
  14. Gulino AV, Moratto D, Sozzani S, et al. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood. 2004;104(2):444–52. doi: 10.1182/blood-2003-10-3532.
  15. Aprikyan AA, Liles WC, Park JR, et al. Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors. Blood. 2000;95(1):320–7. doi: 10.1182/blood.V95.1.320.
  16. McDermott DH, Liu Q, Velez D, et al. A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood. 2014;123(15):2308–16. doi: 10.1182/blood-2013-09-527226.
  17. Balabanian K, Brotin E, Biajoux V, et al. Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice. Blood. 2012;119(24):5722–30. doi: 10.1182/blood-2012-01-403378.
  18. Mentzer WC Jr, Johnston RB Jr, Baehner RL, Nathan DG. An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol. 1977;36(3):313–22. doi: 10.1111/j.1365-2141.1977.tb00654.x.
  19. Badolato R, Donadieu J. How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. Blood. 2017;130(23):2491–8. doi: 10.1182/blood-2017-02-708552.
  20. McGuire PJ, Cunningham-Rundles C, Ochs H, Diaz GA. Oligoclonality, impaired class switch and B-cell memory responses in WHIM syndrome. Clin Immunol. 2010;135(3):412–21. doi: 10.1016/j.clim.2010.02.006.
  21. Handisurya A, Schellenbacher C, Reininger B, et al. A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome. Vaccine. 2010;28(30):4837–41. doi: 10.1016/j.vaccine.2010.04.057.
  22. Roselli G, Martini E, Lougaris V, et al. CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency. Front Immunol. 2017;8:1068. doi: 10.3389/fimmu.2017.01068.
  23. Dotta L, Notarangelo LD, Moratto D, et al. Long-Term Outcome of WHIM Syndrome in 18 Patients: High Risk of Lung Disease and HPV-Related Malignancies. J Allergy Clin Immunol Pract. 2019;7(5):1568–77. doi: 10.1016/j.jaip.2019.01.045.
  24. Chow KY, Brotin Е, Ben Khalifa Y, et al. A pivotal role for CXCL12 signaling in HPV-mediated transformation of keratinocytes: clues to understanding HPV-pathogenesis in WHIM syndrome. Cell Host Microbe. 2010;8(6):523–33. doi: 10.1016/j.chom.2010.11.006.
  25. Meuris F, Carthagena L, Jaracz-Ros A, et al. The CXCL12/CXCR4 Signaling Pathway: A New Susceptibility Factor in Human Papillomavirus Pathogenesis. PLoS Pathog. 2016;12(12):e1006039. doi: 10.1371/journal.ppat.1006039.
  26. McDermott DH, Gao JL, Liu Q, et al. Chromothriptic cure of WHIM syndrome. Cell. 2015;160(4):686–99. doi: 10.1016/j.cell.2015.01.014.
  27. Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. 2011;144(1):27–40. doi: 10.1016/j.cell.2010.11.055.
  28. Мамаев Н.Н., Гиндина Т.Л., Бойченко Э.Г. Хромотрипсис в онкологии: обзор литературы и собственное наблюдение. Клиническая онкогематология. 2017;10(2):191–205. doi: 10.21320/2500-2139-2017-10-2-191-205.
    [Mamaev NN, Gindina TL, Boichenko EG. Chromothripsis in Oncology: Literature Review and Case Report. Clinical oncohematology. 2017;10(2):191–205. doi: 10.21320/2500-2139-2017-10-2-191-205. (In Russ)]
  29. Auer PL, Teumer A, Schick U, et al. Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits. Nat Genet. 2014;46(6):629–34. doi: 10.1038/ng.2962.
  30. Hunter ZR, Xu L, Yang G, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. 2014;123(11):1637–46. doi: 10.1182/blood-2013-09-525808.
  31. Dale DC, Dick E, Kelley M, et al Family studies of warts, hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome. Curr Opin Hematol. 2020;27(1):11–7. doi: 10.1097/MOH.0000000000000554.
  32. Latger-Cannard V, Bensoussan D, Bordigoni P. The WHIM syndrome shows a peculiar dysgranulopoiesis: myelokathexis. Br J Haematol. 2006;132(6):669. doi: 10.1111/j.1365-2141.2005.05908.x.
  33. Kim HK, De La Luz Sierra M, Williams CK, et al. G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells. Blood. 2006;108(3):812–20. doi: 10.1182/blood-2005-10-4162.
  34. Деордиева Е.А., Швец О.А., Лаберко А.Л. и др. Характеристика группы пациентов с WHIM-синдромом. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020;19(4):68–75. doi: 10.24287/1726-1708-2020-19-4suppl-68-75.
    [Deordieva EA, Shvets OA, Laberko AL, et al. Characteristics of a group of patients with WHIM syndrome. Pediatric Hematology/Oncology and Immunopathology. 2020;19(4):68–75. doi: 10.24287/1726-1708-2020-19-4suppl-68-75. (In Russ)]
  35. McDermott DH, Pastrana DV, Calvo KR, et al. Plerixafor for the Treatment of WHIM Syndrome. N Engl J Med. 2019;380(2):163–70. doi: 10.1056/NEJMoa1808575.
  36. Dale DC, Firkin F, Bolyard AA, et al. Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Blood. 2020;136(26):2994–3003. doi: 10.1182/blood.2020007197.
  37. Dale DC, Alsina L, Azar A, et al. Global Phase 3, Randomized, Placebo-Controlled Trial with Open-Label Extension Evaluating the Oral CXCR4 Antagonist Mavorixafor in Patients with WHIM Syndrome (4WHIM): Trial Design and Enrollment. Blood. 2021;138(Suppl 1):4310. doi: 10.1182/blood-2021-153346.
  38. Handisurya A, Schellenbacher C, Reininger B, et al. A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome. Vaccine. 2010;28(30):4837–41. doi: 10.1016/j.vaccine.2010.04.057.
  39. Laberko A, Deordieva E, Krivan G, et al. Multicenter Experience of Hematopoietic Stem Cell Transplantation in WHIM Syndrome. J Clin Immunol. 2022;42(1):171-182 doi: 10.1007/s10875-021-01155-8.
  40. Tarzi MD, Jenner M, Hattotuwa K, et al. Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome. J Allergy Clin Immunol. 2005;116(5):1101–5. doi: 10.1016/j.jaci.2005.08.040.
  41. Badolato R, Dotta L, Tassone L, et al. Tetralogy of Fallot is an uncommon manifestation of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. J Pediatr. 2012;161(4):763–5. doi: 10.1016/j.jpeds.2012.05.058.
  42. McDermott DH, De Ravin SS, Jun HS, et al. Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis. Blood. 2010;116(15):2793–802. doi: 10.1182/blood-2010-01-265942.
  43. Leiding JW, Holland SM. Warts and all: human papillomavirus in primary immunodeficiencies. J Allergy Clin Immunol. 2012;130(5):1030–48. doi: 10.1016/j.jaci.2012.07.049.
  44. Mansour S, Josephs KS, Ostergaard P, et al. Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts. J Med Genet. 2021:jmedgenet-2021–107820. doi: 10.1136/jmedgenet-2021-107820.