Skip to main content
Erschienen in: Journal of Clinical Immunology 3/2019

27.03.2019 | Original Article

Report of a Chinese Cohort with Leukocyte Adhesion Deficiency-I and Four Novel Mutations

verfasst von: Bijun Sun, Qiuyu Chen, Xiaolong Dong, Danru Liu, Jia Hou, Wenjie Wang, Wenjing Ying, Xiaoying Hui, Qinhua Zhou, Haili Yao, Jinqiao Sun, Xiaochuan Wang

Erschienen in: Journal of Clinical Immunology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We aimed to report the characteristics of leukocyte adhesion deficiency-I (LAD-I) and four novel mutations in the ITGB2 gene in a Chinese cohort.

Methods

Seven patients with LAD-I were reported in our study. Clinical manifestations and immunological phenotypes were reviewed. The expression of CD18 was detected by flow cytometry. Next-generation sequencing (NGS) and Sanger sequencing were performed to identify gene mutations.

Results

The mean onset age of all the patients was 1.3 months. Recurrent bacterial infections of the skin and lungs were the most common symptoms. Most patients (6/7) had delayed cord separation. The number of white blood cells (WBC) was increased significantly, except that two patients had a mild increase in the number of WBC during infection-free periods. The expression of CD18 was very low in all patients. Homozygous or compound heterozygous mutations in the ITGB2 gene were identified in each patient. Four mutations were novel, including c.1794dupC (p.N599Qfs*93), c.1788C>A (p.C596X), c.841-849del9, and c.741+1delG. Two patients had large deletions of the ITGB2 gene. Five patients were cured by hematopoietic stem cell transplantation (HSCT).

Conclusions

This study reported the clinical and molecular characteristics of a Chinese patient cohort. It is helpful in understanding the current status of the disease in China.
Literatur
1.
Zurück zum Zitat Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20(1):16–25.PubMedPubMedCentral Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20(1):16–25.PubMedPubMedCentral
2.
Zurück zum Zitat Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007;601:51–60.CrossRefPubMed Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007;601:51–60.CrossRefPubMed
3.
Zurück zum Zitat Movahedi M, Entezari N, Pourpak Z, Mamishi S, Chavoshzadeh Z, Gharagozlou M, et al. Clinical and laboratory findings in Iranian patients with leukocyte adhesion deficiency (study of 15 cases). J Clin Immunol. 2007;27(3):302–7.CrossRefPubMed Movahedi M, Entezari N, Pourpak Z, Mamishi S, Chavoshzadeh Z, Gharagozlou M, et al. Clinical and laboratory findings in Iranian patients with leukocyte adhesion deficiency (study of 15 cases). J Clin Immunol. 2007;27(3):302–7.CrossRefPubMed
4.
Zurück zum Zitat Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, et al. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999;103(1):97–106.CrossRefPubMedPubMedCentral Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, et al. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999;103(1):97–106.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat van de Vijver E, Maddalena A, Sanal O, Holland SM, Uzel G, Madkaikar M, et al. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012;48(1):53–61.CrossRefPubMed van de Vijver E, Maddalena A, Sanal O, Holland SM, Uzel G, Madkaikar M, et al. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012;48(1):53–61.CrossRefPubMed
6.
7.
Zurück zum Zitat van de Vijver E, van den Berg TK, Kuijpers TW. Leukocyte adhesion deficiencies. Hematol Oncol Clin North Am. 2013;27(1):101–16.CrossRefPubMed van de Vijver E, van den Berg TK, Kuijpers TW. Leukocyte adhesion deficiencies. Hematol Oncol Clin North Am. 2013;27(1):101–16.CrossRefPubMed
8.
Zurück zum Zitat Madkaikar M, Italia K, Gupta M, Chavan S, Mishra A, Rao M, et al. Molecular characterization of leukocyte adhesion deficiency-I in Indian patients: identification of 9 novel mutations. Blood Cells Mol Dis. 2015;54(3):217–23.CrossRefPubMed Madkaikar M, Italia K, Gupta M, Chavan S, Mishra A, Rao M, et al. Molecular characterization of leukocyte adhesion deficiency-I in Indian patients: identification of 9 novel mutations. Blood Cells Mol Dis. 2015;54(3):217–23.CrossRefPubMed
9.
Zurück zum Zitat Almarza NE, Kasbekar S, Thrasher AJ, Kohn DB, Sevilla J, Nguyen T, et al. Leukocyte adhesion deficiency-I: a comprehensive review of all published cases. J Allergy Clin Immunol Pract. 2018;6(4):1418–20.CrossRef Almarza NE, Kasbekar S, Thrasher AJ, Kohn DB, Sevilla J, Nguyen T, et al. Leukocyte adhesion deficiency-I: a comprehensive review of all published cases. J Allergy Clin Immunol Pract. 2018;6(4):1418–20.CrossRef
10.
Zurück zum Zitat Liu JR, Zhao SY, Jiang ZF. Clinical analysis of a Chinese child with leukocyte adhesion deficiency type 1[J]. Chin J Pediatr. 2013;51(7):531–4. Liu JR, Zhao SY, Jiang ZF. Clinical analysis of a Chinese child with leukocyte adhesion deficiency type 1[J]. Chin J Pediatr. 2013;51(7):531–4.
11.
Zurück zum Zitat Wang T, Jiang LP, Gao H, Zhao XD. Clinical and molecular features of one case of leukocyte adhesion deficiencytype-1 [J]. Immunol J. 2017;33(8):697–702. Wang T, Jiang LP, Gao H, Zhao XD. Clinical and molecular features of one case of leukocyte adhesion deficiencytype-1 [J]. Immunol J. 2017;33(8):697–702.
12.
Zurück zum Zitat Lin Y, Zheng HY, Xian YY, Chang H, Lei K, Wang BT, et al. Novel mutations of ITGB2 induced leukocyte adhesion defect type 1 [J]. Chin J Pediatr. 2018;56(8):617–22. Lin Y, Zheng HY, Xian YY, Chang H, Lei K, Wang BT, et al. Novel mutations of ITGB2 induced leukocyte adhesion defect type 1 [J]. Chin J Pediatr. 2018;56(8):617–22.
13.
Zurück zum Zitat Tsai YC, Lee WI, Huang JL, Hung IJ, Jaing TH, Yao TC, et al. Neutrophil function and molecular analysis in severe leukocyte adhesion deficiency type I without separation delay of the umbilical cord. Pediatr Allergy Immunol. 2008;19(1):25–32.PubMed Tsai YC, Lee WI, Huang JL, Hung IJ, Jaing TH, Yao TC, et al. Neutrophil function and molecular analysis in severe leukocyte adhesion deficiency type I without separation delay of the umbilical cord. Pediatr Allergy Immunol. 2008;19(1):25–32.PubMed
14.
Zurück zum Zitat Wang Y, Wang W, Liu L, Hou J, Ying W, Hui X, et al. Report of a Chinese cohort with activated phosphoinositide 3-kinase delta syndrome. J Clin Immunol. 2018;38(8):854–63.CrossRefPubMed Wang Y, Wang W, Liu L, Hou J, Ying W, Hui X, et al. Report of a Chinese cohort with activated phosphoinositide 3-kinase delta syndrome. J Clin Immunol. 2018;38(8):854–63.CrossRefPubMed
15.
Zurück zum Zitat Wang J, Yu H, Zhang VW, Tian X, Feng Y, Wang G, et al. Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types. Genet Med. 2016;18(5):513–21.CrossRefPubMed Wang J, Yu H, Zhang VW, Tian X, Feng Y, Wang G, et al. Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types. Genet Med. 2016;18(5):513–21.CrossRefPubMed
16.
Zurück zum Zitat Hayward AR, Harvey BA, Leonard J, Greenwood MC, Wood CB, Soothill JF. Delayed separation of the umbilical cord, widespread infections, and defective neutrophil mobility. Lancet. 1979;1(8126):1099–101.CrossRefPubMed Hayward AR, Harvey BA, Leonard J, Greenwood MC, Wood CB, Soothill JF. Delayed separation of the umbilical cord, widespread infections, and defective neutrophil mobility. Lancet. 1979;1(8126):1099–101.CrossRefPubMed
17.
Zurück zum Zitat Springer TA, Thompson WS, Miller LJ, Schmalstieg FC, Anderson DC. Inherited deficiency of the Mac-1, LFA-1, p150, 95 glycoprotein family and its molecular basis. J Exp Med. 1984;160(6):1901–18.CrossRefPubMed Springer TA, Thompson WS, Miller LJ, Schmalstieg FC, Anderson DC. Inherited deficiency of the Mac-1, LFA-1, p150, 95 glycoprotein family and its molecular basis. J Exp Med. 1984;160(6):1901–18.CrossRefPubMed
18.
Zurück zum Zitat Tewari N, Mathur VP, Yadav VS, Chaudhari P. Leukocyte adhesion defect-I: rare primary immune deficiency. Spec Care Dentist. 2017;37(6):309–13.CrossRefPubMed Tewari N, Mathur VP, Yadav VS, Chaudhari P. Leukocyte adhesion defect-I: rare primary immune deficiency. Spec Care Dentist. 2017;37(6):309–13.CrossRefPubMed
19.
Zurück zum Zitat Etzioni A. Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol. 2009;21(5):481–6.CrossRefPubMed Etzioni A. Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol. 2009;21(5):481–6.CrossRefPubMed
20.
Zurück zum Zitat Cox DP, Weathers DR. Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(1):86–90.CrossRefPubMed Cox DP, Weathers DR. Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(1):86–90.CrossRefPubMed
21.
Zurück zum Zitat Majorana A, Notarangelo LD, Savoldi E, Gastaldi G, Lozada-Nur F. Leukocyte adhesion deficiency in a child with severe oral involvement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87(6):691–4.CrossRefPubMed Majorana A, Notarangelo LD, Savoldi E, Gastaldi G, Lozada-Nur F. Leukocyte adhesion deficiency in a child with severe oral involvement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87(6):691–4.CrossRefPubMed
22.
Zurück zum Zitat Teimourian S, De Boer M, Roos D, Isaian A, Bemanian MH, Lashkary S, et al. Genetic analysis of 13 Iranian families with leukocyte adhesion deficiency type 1. J Pediatr Hematol Oncol. 2018. Teimourian S, De Boer M, Roos D, Isaian A, Bemanian MH, Lashkary S, et al. Genetic analysis of 13 Iranian families with leukocyte adhesion deficiency type 1. J Pediatr Hematol Oncol. 2018.
23.
Zurück zum Zitat Deshpande P, Kathirvel K, Alex AA, Korula A, George B, Shaji RV, et al. Leukocyte adhesion deficiency-I: clinical and molecular characterization in an Indian population. Indian J Pediatr. 2016;83(8):799–804.CrossRefPubMed Deshpande P, Kathirvel K, Alex AA, Korula A, George B, Shaji RV, et al. Leukocyte adhesion deficiency-I: clinical and molecular characterization in an Indian population. Indian J Pediatr. 2016;83(8):799–804.CrossRefPubMed
24.
Zurück zum Zitat Madkaikar MR, Gupta M, Rao M, Ghosh K. Prenatal diagnosis of LAD-I on cord blood by flowcytometry. Indian J Pediatr. 2012;79(12):1605–9.CrossRefPubMed Madkaikar MR, Gupta M, Rao M, Ghosh K. Prenatal diagnosis of LAD-I on cord blood by flowcytometry. Indian J Pediatr. 2012;79(12):1605–9.CrossRefPubMed
25.
Zurück zum Zitat Wolach B, Gavrieli R, Wolach O, Stauber T, Abuzaitoun O, Kuperman A, et al. Leucocyte adhesion deficiency-a multicentre national experience. Eur J Clin Investig. 2019;49(2):e13047.CrossRef Wolach B, Gavrieli R, Wolach O, Stauber T, Abuzaitoun O, Kuperman A, et al. Leucocyte adhesion deficiency-a multicentre national experience. Eur J Clin Investig. 2019;49(2):e13047.CrossRef
26.
Zurück zum Zitat Bernard CT, Chan HS, Klein GF, Jabkowski J, Schadenbock-Kranzl G, Zach O, et al. A novel 3’ splice-site mutation and a novel gross deletion in leukocyte adhesion deficiency (LAD)-1. Biochem Biophys Res Commun. 2011;404(4):1099–104.CrossRef Bernard CT, Chan HS, Klein GF, Jabkowski J, Schadenbock-Kranzl G, Zach O, et al. A novel 3’ splice-site mutation and a novel gross deletion in leukocyte adhesion deficiency (LAD)-1. Biochem Biophys Res Commun. 2011;404(4):1099–104.CrossRef
27.
Zurück zum Zitat Fiorini M, Piovani G, Schumacher RF, Magri C, Bertini V, Mazzolari E, et al. ITGB2 mutation combined with deleted ring 21 chromosome in a child with leukocyte adhesion deficiency. J Allergy Clin Immunol. 2009;124(6):1356–8.CrossRefPubMed Fiorini M, Piovani G, Schumacher RF, Magri C, Bertini V, Mazzolari E, et al. ITGB2 mutation combined with deleted ring 21 chromosome in a child with leukocyte adhesion deficiency. J Allergy Clin Immunol. 2009;124(6):1356–8.CrossRefPubMed
28.
Zurück zum Zitat Roos D, Meischl C, de Boer M, Simsek S, Weening RS, Sanal O, et al. Genetic analysis of patients with leukocyte adhesion deficiency: genomic sequencing reveals otherwise undetectable mutations. Exp Hematol. 2002;30(3):252–61.CrossRefPubMed Roos D, Meischl C, de Boer M, Simsek S, Weening RS, Sanal O, et al. Genetic analysis of patients with leukocyte adhesion deficiency: genomic sequencing reveals otherwise undetectable mutations. Exp Hematol. 2002;30(3):252–61.CrossRefPubMed
29.
Zurück zum Zitat Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, et al. Interleukin-12 and Interleukin-23 blockade in leukocyte adhesion deficiency type 1. N Engl J Med. 2017;376(12):1141–6.CrossRefPubMedPubMedCentral Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, et al. Interleukin-12 and Interleukin-23 blockade in leukocyte adhesion deficiency type 1. N Engl J Med. 2017;376(12):1141–6.CrossRefPubMedPubMedCentral
Metadaten
Titel
Report of a Chinese Cohort with Leukocyte Adhesion Deficiency-I and Four Novel Mutations
verfasst von
Bijun Sun
Qiuyu Chen
Xiaolong Dong
Danru Liu
Jia Hou
Wenjie Wang
Wenjing Ying
Xiaoying Hui
Qinhua Zhou
Haili Yao
Jinqiao Sun
Xiaochuan Wang
Publikationsdatum
27.03.2019
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 3/2019
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-019-00617-4

Weitere Artikel der Ausgabe 3/2019

Journal of Clinical Immunology 3/2019 Zur Ausgabe

CME Review

CAPS and NLRP3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.