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Open Access 10-08-2022 | Neutropenia | Original Article

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Authors: Christoph B. Geier, Maryssa Ellison, Rachel Cruz, Sumit Pawar, Alexander Leiss-Piller, Katarina Zmajkovicova, Shannon M McNulty, Melis Yilmaz, Martin Oman Evans 2nd, Sumai Gordon, Boglarka Ujhazi, Ivana Wiest, Hassan Abolhassani, Asghar Aghamohammadi, Sara Barmettler, Saleh Bhar, Anastasia Bondarenko, Audrey Anna Bolyard, David Buchbinder, Michaela Cada, Mirta Cavieres, James A. Connelly, David C. Dale, Ekaterina Deordieva, Morna J. Dorsey, Simon B. Drysdale, Stephan Ehl, Reem Elfeky, Francesca Fioredda, Frank Firkin, Elizabeth Förster-Waldl, Bob Geng, Vera Goda, Luis Gonzalez-Granado, Eyal Grunebaum, Elzbieta Grzesk, Sarah E. Henrickson, Anna Hilfanova, Mitsuteru Hiwatari, Chihaya Imai, Winnie Ip, Soma Jyonouchi, Hirokazu Kanegane, Yuta Kawahara, Amer M. Khojah, Vy Hong-Diep Kim, Marina Kojić, Sylwia Kołtan, Gergely Krivan, Daman Langguth, Yu-Lung Lau, Daniel Leung, Maurizio Miano, Irina Mersyanova, Talal Mousallem, Mica Muskat, Flavio A. Naoum, Suzie A. Noronha, Monia Ouederni, Shuichi Ozono, G. Wendell Richmond, Inga Sakovich, Ulrich Salzer, Catharina Schuetz, Filiz Odabasi Seeborg, Svetlana O. Sharapova, Katja Sockel, Alla Volokha, Malte von Bonin, Klaus Warnatz, Oliver Wegehaupt, Geoffrey A. Weinberg, Ke-Juin Wong, Austen Worth, Huang Yu, Yulia Zharankova, Xiaodong Zhao, Lisa Devlin, Adriana Badarau, Krisztian Csomos, Marton Keszei, Joao Pereira, Arthur G Taveras, Sarah L. Beaussant-Cohen, Mei-Sing Ong, Anna Shcherbina, Jolan E. Walter

Published in: Journal of Clinical Immunology | Issue 8/2022

Abstract

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

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Auer PL, Teumer A, Schick U, O’Shaughnessy A, Lo KS, Chami N, et al. Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits. Nat Genet [Internet]. 2014;46:629–34 Nature Publishing Group; [cited 2021 Jan 17];Available from: https://pubmed.ncbi.nlm.nih.gov/24777453/.CrossRefPubMed

Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet [Internet]. Nat Genet; 2003 34:70–4 [cited 2020 Oct 13]; Available from: https://pubmed.ncbi.nlm.nih.gov/12692554/

Moscato GMF, Giacobbi E, Anemona L, Di Cesare S, Di Matteo G, Andreoni M, et al. Dysplasia of granulocytes in a patient with HpV disease, recurrent infections, and B Lymphopenia: A novel variant of WHIM syndrome? Front Pediatr [Internet]. Frontiers Media S.A.; 2017 [cited 2021 Jan 20];5. Available from: https://pubmed.ncbi.nlm.nih.gov/28512628/

Kawai T, Malech HL. WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol [Internet]. Curr Opin Hematol. 2009;16:20–6 [cited 2021 Dec 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/19057201/.CrossRefPubMedPubMedCentral

Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM. WHIM syndrome: from pathogenesis towards personalized medicine and cure [Internet]. J. Clin. Immunol. Springer New York LLC; 2019 [cited 2020 Oct 13]. p. 532–56. Available from: https://pubmed.ncbi.nlm.nih.gov/31313072/

Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest [Internet]. J Clin Invest. 2010;120:2423–31 [cited 2021 Jan 17]; Available from: https://pubmed.ncbi.nlm.nih.gov/20516641/.CrossRefPubMedPubMedCentral

McDermott DH, Murphy PM. WHIM syndrome: Immunopathogenesis, treatment and cure strategies [Internet]. Immunol. Rev. Blackwell Publishing Ltd; 2019 [cited 2020 Oct 13]. p. 91–102. Available from: https://pubmed.ncbi.nlm.nih.gov/30565238/

ZUELZER WW. “Myelokathexis”--a new form of chronic granulocytopenia. Report of a case. N Engl J Med [Internet]. N Engl J Med. 1964;270:699–704 [cited 2020 Oct 13]; Available from: https://pubmed.ncbi.nlm.nih.gov/14101065/.CrossRefPubMed

Latger-Cannard V, Bensoussan D, Bordigoni P. The WHIM syndrome shows a peculiar dysgranulopoiesis: Myelokathexis. Br J Haematol [Internet]. Br J Haematol; 2006 [cited 2021 Jan 17];132:669. Available from: https://pubmed.ncbi.nlm.nih.gov/16487166/

10.

Dotta L, Notarangelo LD, Moratto D, Kumar R, Porta F, Soresina A, 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 [Internet]. American Academy of Allergy, Asthma and Immunology. 2019;7:1568–77 [cited 2020 Oct 18]; Available from: https://pubmed.ncbi.nlm.nih.gov/30716504/.

11.

Badolato R, Dotta L, Tassone L, Amendola G, Porta F, Locatelli F, et al. Tetralogy of fallot is an uncommon manifestation of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. J Pediatr [Internet]. J Pediatr. 2012;161:763–5 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/22748845/.CrossRefPubMedPubMedCentral

12.

Milanesi S, Locati M, Borroni EM. Aberrant CXCR4 signaling at crossroad of WHIM syndrome and Waldenstrom’s macroglobulinemia [Internet]. Int J Mol Sci. MDPI AG; 2020 [cited 2020 Oct 27]. p. 1–15. Available from: https://pubmed.ncbi.nlm.nih.gov/32784523/

13.

Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res. Academic Press Inc.; 2014. p. 31–82.

14.

Dale DC, Dick E, Kelley M, Makaryan V, Connelly J, Bolyard AA. Family studies of warts, hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome [Internet]. Curr. Opin. Hematol. Lippincott Williams and Wilkins; 2020 [cited 2021 Jan 6]. p. 11–7. Available from: https://pubmed.ncbi.nlm.nih.gov/31652152/

15.

Majumdar S, Murphy PM. Adaptive immunodeficiency in WHIM syndrome [Internet]. Int. J. Mol. Sci. MDPI AG; 2019 [cited 2020 Oct 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/30577453/

16.

Beaussant Cohen S, Fenneteau O, Plouvier E, Rohrlich PS, Daltroff G, Plantier I, 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 [Internet]. Orphanet J Rare Dis; 2012 [cited 2020 Oct 18];7. Available from: https://pubmed.ncbi.nlm.nih.gov/23009155/

17.

Badolato R, Donadieu J, Dotta L, Beaussant Cohen S. How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome [Internet]. Blood. American Society of Hematology; 2017 [cited 2020 Oct 27]. p. 2491–8. Available from: https://pubmed.ncbi.nlm.nih.gov/29066537/

18.

Silva LM, Brenchley L, Moutsopoulos NM. Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis [Internet]. Immunol. Rev. Blackwell Publishing Ltd; 2019 [cited 2021 Jan 17]. p. 226–35. Available from: https://pubmed.ncbi.nlm.nih.gov/30565245/

19.

Dale DC, Firkin FC, Bolyard AA, Kelley M, Makaryan V, Gorelick KJ, et al. Results of a phase 2 trial of an oral CXCR4 antagonist mavorixafor for treatment of WHIM syndrome. Blood [Internet]. American Society of Hematology; 2020 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/32870250/

20.

McDermott DH, Pastrana DV, Calvo KR, Pittaluga S, Velez D, Cho E, et al. Plerixafor for the treatment of WHIM syndrome. N Engl J Med [Internet]. New England Journal of Medicine (NEJM/MMS). 2019;380:163–70 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/30625055/.CrossRef

21.

Naoum FA. A report of WHIM syndrome (Myelokathexis) - clinical features and bone marrow morphology [Internet]. Rev. Bras. Hematol. Hemoter. Rev Bras Hematol Hemoter; 2011 [cited 2020 Oct 27]. p. 393–4. Available from: https://pubmed.ncbi.nlm.nih.gov/23049346/

22.

Mentzer WC, Johnston RB, Baehner RL, Nathan DG. An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol [Internet]. Br J Haematol. 1977;36:313–22 [cited 2020 Oct 13]; Available from: https://pubmed.ncbi.nlm.nih.gov/889707/.CrossRefPubMed

23.

O’regan S, Newman AJ, Graham RC. ‘Myelokathexis’: neutropenia with narrow hyperplasia. Am J Dis Child [Internet]. Am J Dis Child. 1977;131:655–8 [cited 2020 Oct 18]; Available from: https://pubmed.ncbi.nlm.nih.gov/868817/.CrossRefPubMed

24.

Prince AER, Berkman BE. When does an illness begin: genetic discrimination and disease manifestation. J Law Med Ethics [Internet]. NIH Public Access; 2012 [cited 2021 Jul 19];40:655. Available from: /pmc/articles/PMC4142506/

25.

Kawahara Y, Oh Y, Kato T, Zaha K, Morimoto A. Transient marked increase of γδ T cells in WHIM syndrome after successful HSCT [Internet]. J. Clin. Immunol. Springer New York LLC; 2018 [cited 2020 Oct 26]. p. 553–5. Available from: https://link.springer.com/article/10.1007/s10875-018-0529-4

26.

Evans MO, McDermott DH, Murphy PM, Petersen MM. Abnormal newborn screen in a WHIM syndrome infant [Internet]. J. Clin. Immunol. Springer New York LLC; 2019 [cited 2020 Oct 26]. p. 839–41. Available from: https://pubmed.ncbi.nlm.nih.gov/31493092/

27.

Aghamohammadi A, Abolhassani H, Puchalka J, Greif-Kohistani N, Zoghi S, Klein C, et al. Preference of genetic diagnosis of CXCR4 mutation compared with clinical diagnosis of WHIM syndrome [Internet]. J. Clin. Immunol. Springer New York LLC; 2017 [cited 2020 Oct 27]. p. 282–6. Available from: https://pubmed.ncbi.nlm.nih.gov/28353164/

28.

Kriván G, Erdos M, Kállay K, Benyó G, Tóth Á, Sinkó J, et al. Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome [Internet]. Eur J Haematol Eur J Haematol; 2010 [cited 2020 Oct 26]. p. 274–5. Available from: https://pubmed.ncbi.nlm.nih.gov/19878273/

29.

Handisurya A, Schellenbacher C, Reininger B, Koszik F, Vyhnanek P, Heitger A, et al. A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome. Vaccine [Internet]. Vaccine. 2010;28:4837–41 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/20472031/.CrossRefPubMedPubMedCentral

30.

Mellouli F, Mustapha IB, Khaled MB, Besbes H, Ouederni M, Mekki N, et al. Report of the Tunisian Registry of Primary Immunodeficiencies: 25-years of experience (1988–2012). J Clin Immunol [Internet]. 2015;35:745–53 Springer New York LLC; [cited 2021 Jan 21]; Available from: https://pubmed.ncbi.nlm.nih.gov/26464197/.CrossRefPubMed

31.

Evans MO, Petersen MM, Khojah A, Jyonouchi SC, Edwardson GS, Khan YW, et al. TREC screening for WHIM syndrome. J Clin Immunol [Internet]. Springer; 2021 [cited 2021 Jan 17]; Available from: https://pubmed.ncbi.nlm.nih.gov/33415666/

32.

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood [Internet]. American Society of. Hematology. 2009;113:2386–93 [cited 2021 Sep 24]; Available from: http://ashpublications.org/blood/article-pdf/113/11/2386/1479268/zh801109002386.pdf.

33.

Hill QA, Hill A, Berentsen S. Defining autoimmune hemolytic anemia: a systematic review of the terminology used for diagnosis and treatment. Blood Adv [Internet]. The American Society of. Hematology. 2019;3:1897 [cited 2021 Sep 24]; Available from: /pmc/articles/PMC6595261/.

34.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med [Internet]. Genet Med. 2015;17:405–24 [cited 2021 Dec 8]; Available from: https://pubmed.ncbi.nlm.nih.gov/25741868/.CrossRefPubMedPubMedCentral

35.

Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG, et al. Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion. Hum Mutat [Internet]. Hum Mutat. 2018;39:1517–24 [cited 2021 Dec 8]; Available from: https://pubmed.ncbi.nlm.nih.gov/30192042/.CrossRefPubMedPubMedCentral

36.

Brnich SE, Abou Tayoun AN, Couch FJ, Cutting GR, Greenblatt MS, Heinen CD, et al. Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework. Genome Med [Internet]. Genome Med; 2019 [cited 2021 Dec 8];12. Available from: https://pubmed.ncbi.nlm.nih.gov/31892348/

37.

Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet [Internet]. Nat Genet. 2014;46:310–5 [cited 2021 Sep 7]; Available from: https://pubmed.ncbi.nlm.nih.gov/24487276/.CrossRefPubMedPubMedCentral

38.

Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher MCADD. predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res [Internet]. Nucleic Acids Res. 2019;47:D886–94 [cited 2021 Sep 7]; Available from: https://pubmed.ncbi.nlm.nih.gov/30371827/.CrossRefPubMed

39.

Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature [Internet]. Nature. 2020;581:434–43 [cited 2021 Dec 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/32461654/.CrossRefPubMedPubMedCentral

40.

Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, et al. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood [Internet]. Blood. 2005;105:2449–57 [cited 2021 Dec 8]; Available from: https://pubmed.ncbi.nlm.nih.gov/15536153/.CrossRefPubMed

41.

Mcdermott DH, Lopez J, Deng F, Liu Q, Ojode T, Chen H, et al. AMD3100 is a potent antagonist at CXCR4(R334X), a hyperfunctional mutant chemokine receptor and cause of WHIM syndrome. J Cell Mol Med [Internet]. J Cell Mol Med. 2011;15:2071–81 [cited 2021 Dec 8]; Available from: https://pubmed.ncbi.nlm.nih.gov/21070597/.CrossRefPubMedPubMedCentral

42.

Liu Q, Chen H, Ojode T, Gao X, Anaya-O’Brien S, Turner NA, et al. WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4. Blood [Internet]. The American Society of. Hematology. 2012;120:181 [cited 2021 Dec 8]; Available from: /pmc/articles/PMC3390956/.

43.

Laberko A, Deordieva E, Krivan G, Goda V, Bhar S, Kawahara Y, et al. Multicenter experience of hematopoietic stem cell transplantation in WHIM syndrome. J Clin Immunol [Internet]. J Clin Immunol; 2021 [cited 2021 Dec 8]; Available from: https://pubmed.ncbi.nlm.nih.gov/34697698/

44.

Tiggelaar SM, Lin MJ, Viscidi RP, Ji J, Smith JS. Age-specific human papillomavirus antibody and deoxyribonucleic acid prevalence: a global review [Internet]. J. Adolesc. Heal. NIH Public Access; 2012 [cited 2020 Oct 30]. p. 110–31. Available from: /pmc/articles/PMC3572199/?report=abstract

45.

Hord JD, Whitlock JA, Gay JC, Lukens JN. Clinical features of myelokathexis and treatment with hematopoietic cytokines: a case report of two patients and review of the literature. J Pediatr Hematol Oncol [Internet]. J Pediatr Hematol Oncol. 1997;19:443–8 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/9329467/.CrossRefPubMed

46.

Tassone L, Notarangelo LDLD, Bonomi V, Savoldi G, Sensi A, Soresina A, et al. Clinical and genetic diagnosis of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome in 10 patients [Internet]. J Allergy Clin Immunol Mosby Inc.; 2009 [cited 2020 Oct 20]. Available from: https://pubmed.ncbi.nlm.nih.gov/19321197/

47.

Evans MO, Petersen MM, Khojah A, Jyonouchi S, Edwardson GS, Kahn YW, et al. A report of 6 WHIM syndrome patients born after implementation of TREC screening. J Clin Immunol. 2020; Available from: https://pubmed.ncbi.nlm.nih.gov/33415666/

48.

Mueller W, Schütz D, Nagel F, Schulz S, Stumm R. Hierarchical organization of multi-site phosphorylation at the CXCR4 C terminus. PLoS One [Internet]. PLoS One; 2013 [cited 2021 Dec 8];8. Available from: https://pubmed.ncbi.nlm.nih.gov/23734232/

49.

Walter JE, Ayala IA, Milojevic D. Autoimmunity as a continuum in primary immunodeficiency [Internet]. Curr. Opin. Pediatr. Lippincott Williams and Wilkins; 2019 [cited 2020 Oct 29]. p. 851–62. Available from: https://pubmed.ncbi.nlm.nih.gov/31693597/

50.

Thalhammer J, Kindle G, Nieters A, Rusch S, Seppänen MRJ, Fischer A, et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. J Allergy Clin Immunol [Internet]. J Allergy Clin Immunol. 2021;148:1332–1341.e5 [cited 2022 Jan 10]; Available from: https://pubmed.ncbi.nlm.nih.gov/33895260/.CrossRefPubMed

51.

Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Adoue D, et al. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140:1388–1393.e8 Mosby Inc.CrossRefPubMed

52.

Kallikourdis M, Trovato AE, Anselmi F, Sarukhan A, Roselli G, Tassone L, et al. The CXCR4 mutations in WHIM syndrome impair the stability of the T-cell immunologic synapse. Blood [Internet]. Blood. 2013;122:666–73 [cited 2020 Oct 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/23794067/.CrossRefPubMedPubMedCentral

53.

Mc Guire PJ, Cunningham-Rundles C, Ochs H, Diaz GA. Oligoclonality, impaired class switch and B-cell memory responses in WHIM syndrome. Clin Immunol [Internet]. Clin Immunol. 2010;135:412–21 [cited 2020 Oct 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/20226738/.CrossRefPubMedPubMedCentral

54.

Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR. WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet [Internet]. 2000;91:368–76 [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/10767001/.CrossRefPubMed

55.

Beck TC, Gomes AC, Cyster JG. Pereira JP. CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. J Exp Med [Internet]. 2014;211:2567–81 Rockefeller University Press; [cited 2020 Oct 26];Available from: https://pubmed.ncbi.nlm.nih.gov/25403444/.CrossRefPubMed

56.

Cassani B, Poliani PL, Marrella V, Schena F, Sauer AV, Ravanini M, et al. Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome. J Exp Med [Internet]. J Exp Med. 2010;207:1525–40 [cited 2020 Jul 30]; Available from: https://pubmed.ncbi.nlm.nih.gov/20547828/.CrossRefPubMedPubMedCentral

57.

Walter JE, Rucci F, Patrizi L, Recher M, Regenass S, Paganini T, et al. Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency. J Exp Med [Internet]. J Exp Med. 2010;207:1541–54 [cited 2020 Jul 30]; Available from: https://pubmed.ncbi.nlm.nih.gov/20547827/.CrossRefPubMedPubMedCentral

58.

Launay O, Paul S, Servettaz A, Roguet G, Rozenberg F, Lucht F, et al. Control of humoral immunity and auto-immunity by the CXCR4/CXCL12 axis in lupus patients following influenza vaccine [Internet]. Vaccine. Vaccine; 2013 [cited 2020 Oct 22]. p. 3492–501. Available from: https://pubmed.ncbi.nlm.nih.gov/23764537/

59.

Kurosawa M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Sprent J, et al. NF-κB2 controls the migratory activity of memory T cells by regulating expression of CXCR4 in a mouse model of Sjögren’s syndrome. Arthritis Rheumatol [Internet]. 2017;69:2193–202 John Wiley and Sons Inc.; [cited 2020 Oct 27]; Available from: https://pubmed.ncbi.nlm.nih.gov/28804991/.CrossRefPubMed

Title: Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients
Authors: Christoph B. Geier
Maryssa Ellison
Rachel Cruz
Sumit Pawar
Alexander Leiss-Piller
Katarina Zmajkovicova
Shannon M McNulty
Melis Yilmaz
Martin Oman Evans 2nd
Sumai Gordon
Boglarka Ujhazi
Ivana Wiest
Hassan Abolhassani
Asghar Aghamohammadi
Sara Barmettler
Saleh Bhar
Anastasia Bondarenko
Audrey Anna Bolyard
David Buchbinder
Michaela Cada
Mirta Cavieres
James A. Connelly
David C. Dale
Ekaterina Deordieva
Morna J. Dorsey
Simon B. Drysdale
Stephan Ehl
Reem Elfeky
Francesca Fioredda
Frank Firkin
Elizabeth Förster-Waldl
Bob Geng
Vera Goda
Luis Gonzalez-Granado
Eyal Grunebaum
Elzbieta Grzesk
Sarah E. Henrickson
Anna Hilfanova
Mitsuteru Hiwatari
Chihaya Imai
Winnie Ip
Soma Jyonouchi
Hirokazu Kanegane
Yuta Kawahara
Amer M. Khojah
Vy Hong-Diep Kim
Marina Kojić
Sylwia Kołtan
Gergely Krivan
Daman Langguth
Yu-Lung Lau
Daniel Leung
Maurizio Miano
Irina Mersyanova
Talal Mousallem
Mica Muskat
Flavio A. Naoum
Suzie A. Noronha
Monia Ouederni
Shuichi Ozono
G. Wendell Richmond
Inga Sakovich
Ulrich Salzer
Catharina Schuetz
Filiz Odabasi Seeborg
Svetlana O. Sharapova
Katja Sockel
Alla Volokha
Malte von Bonin
Klaus Warnatz
Oliver Wegehaupt
Geoffrey A. Weinberg
Ke-Juin Wong
Austen Worth
Huang Yu
Yulia Zharankova
Xiaodong Zhao
Lisa Devlin
Adriana Badarau
Krisztian Csomos
Marton Keszei
Joao Pereira
Arthur G Taveras
Sarah L. Beaussant-Cohen
Mei-Sing Ong
Anna Shcherbina
Jolan E. Walter
Publication date: 10-08-2022
Publisher: Springer US
Keywords: Neutropenia
Lymphopenia
Wart
Published in: Journal of Clinical Immunology / Issue 8/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01312-7

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