nach oben

Erschienen in:

11.06.2019 | Original Article

Respiratory Complications in Patients with Hyper IgM Syndrome

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome.

Methods

A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans.

Results

Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%).

Conclusions

Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

Nur mit Berechtigung zugänglich

Conley ME, Larche M, Bonagura VR, Lawton AR 3rd, Buckley RH, Fu SM, et al. Hyper IgM syndrome associated with defective CD40-mediated B cell activation. J Clin Invest. 1994;94(4):1404–9. https://doi.org/10.1172/jci117476.CrossRefPubMedPubMedCentral

Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101–21.PubMed

Qamar N, Fuleihan RL. The hyper IgM syndromes. Clin Rev Allergy Immunol. 2014;46(2):120–30. https://doi.org/10.1007/s12016-013-8378-7.CrossRefPubMed

Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine. 2003;82(6):373–84. https://doi.org/10.1097/01.md.0000100046.06009.b0.CrossRefPubMed

Durandy A, Kracker S. Immunoglobulin class-switch recombination deficiencies. Arthritis Res Ther. 2012;14(4):218. https://doi.org/10.1186/ar3904.CrossRefPubMedPubMedCentral

Aghamohammadi A, Parvaneh N, Rezaei N, Moazzami K, Kashef S, Abolhassani H, et al. Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations. J Clin Immunol. 2009;29(6):769–76. https://doi.org/10.1007/s10875-009-9315-7.CrossRefPubMed

Hirbod-Mobarakeh A, Aghamohammadi A, Rezaei N. Immunoglobulin class switch recombination deficiency type 1 or CD40 ligand deficiency: from bedside to bench and back again. Expert Rev Clin Immunol. 2014;10(1):91–105.CrossRef

Abolhassani H, Parvaneh N, Rezaei N, Hammarstrom L, Aghamohammadi A. Genetic defects in B-cell development and their clinical consequences. J Investig Allergol Clin Immunol. 2014;24(1):6–22 quiz 2 p following.PubMed

Peron S, Metin A, Gardes P, Alyanakian MA, Sheridan E, Kratz CP, et al. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. J Exp Med. 2008;205(11):2465–72. https://doi.org/10.1084/jem.20080789.CrossRefPubMedPubMedCentral

10.

Leven EA, Maffucci P, Ochs HD, Scholl PR, Buckley RH, Fuleihan RL, et al. Hyper IgM Syndrome: a report from the USIDNET Registry. J Clin Immunol. 2016;36(5):490–501. https://doi.org/10.1007/s10875-016-0291-4.CrossRefPubMedPubMedCentral

11.

Noordzij JG, Wulffraat NM, Haraldsson A, Meyts I, van't Veer LJ, Hogervorst FB, et al. Ataxia-telangiectasia patients presenting with hyper-IgM syndrome. Arch Dis Child. 2009;94(6):448–9. https://doi.org/10.1136/adc.2008.149351.CrossRefPubMed

12.

Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International union of immunological societies: 2017 primary mmunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128. https://doi.org/10.1007/s10875-017-0464-9.CrossRefPubMed

13.

Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, et al. Clinical spectrum of X-linked hyper-IgM syndrome. J Pediatr. 1997;131(1 Pt 1):47–54.CrossRef

14.

Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2). Cell. 2000;102(5):565–75.CrossRef

15.

Minegishi Y, Lavoie A, Cunningham-Rundles C, Bedard PM, Hebert J, Cote L, et al. Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome. Clin Immunol (Orlando, Fla). 2000;97(3):203–10. https://doi.org/10.1006/clim.2000.4956.CrossRef

16.

Azizi G, Abolhassani H, Rezaei N, Aghamohammadi A, Asgardoon MH, Rahnavard J, et al. The use of immunoglobulin therapy in primary immunodeficiency diseases. Endocr Metab Immune Disord Drug Targets. 2016;24(77293):EPUB-77293.

17.

de la Morena MT. Clinical phenotypes of hyper-IgM syndromes. J Allergy Clin Immunol Pract. 2016;4(6):1023–36. https://doi.org/10.1016/j.jaip.2016.09.013.CrossRefPubMed

18.

Dosanjh A. Chronic pediatric pulmonary disease and primary humoral antibody based immune disease. Respir Med. 2011;105(4):511–4. https://doi.org/10.1016/j.rmed.2010.11.013.CrossRefPubMed

19.

Abolhassani H, Akbari F, Mirminachi B, Bazregari S, Hedayat E, Rezaei N, et al. Morbidity and mortality of Iranian patients with hyper IgM syndrome: a clinical analysis. Iran J Immunol. 2014;11(2):123–33.PubMed

20.

de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, et al. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. J Allergy Clin Immunol. 2017;139(4):1282–92.CrossRef

21.

Abolhassani H, Aghamohammadi A, Fang M, Rezaei N, Jiang C, Liu X, et al. Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency. Genet Med. 2018. https://doi.org/10.1038/s41436-018-0012-x.

22.

Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, et al. Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency. J Allergy Clin Immunol. 2018;141(4):1450–8. https://doi.org/10.1016/j.jaci.2017.06.049.CrossRefPubMed

23.

Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, et al. Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry. J Clin Immunol. 2014;34(4):478–90. https://doi.org/10.1007/s10875-014-0001-z.CrossRefPubMed

24.

Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth Update on the Iranian national registry of primary immunodeficiencies: integration of molecular diagnosis. J Clin Immunol. 2018;38(7):816–32. https://doi.org/10.1007/s10875-018-0556-1.CrossRefPubMed

25.

Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16(3):128–40.CrossRef

26.

Bhalla M, Turcios N, Aponte V, Jenkins M, Leitman BS, McCauley DI, et al. Cystic fibrosis: scoring system with thin-section CT. Radiology. 1991;179(3):783–8.CrossRef

27.

Grenier P, Cordeau MP, Beigelman C. High-resolution computed tomography of the airways. J Thorac Imaging. 1993;8(3):213–29.CrossRef

28.

Hansell DM, Wells AU, Rubens MB, Cole PJ. Bronchiectasis: functional significance of areas of decreased attenuation at expiratory CT. Radiology. 1994;193(2):369–74. https://doi.org/10.1148/radiology.193.2.7972745.CrossRefPubMed

29.

Gharagozlou M, Ebrahimi FA, Farhoudi A, Aghamohammadi A, Bemanian MH, Chavoshzadeh Z, et al. Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan. Monaldi Arch Chest Dis. 2006;65(2):69–74.PubMed

30.

Rusconi F, Panisi C, Dellepiane RM, Cardinale F, Chini L, Martire B, et al. Pulmonary and sinus diseases in primary humoral immunodeficiencies with chronic productive cough. Arch Dis Child. 2003;88(12):1101–5.CrossRef

31.

van Zeggeren L, van de Ven AA, Terheggen-Lagro SW, Mets OM, Beek FJ, van Montfrans JM, et al. High-resolution computed tomography and pulmonary function in children with common variable immunodeficiency. Eur Respir J. 2011;38(6):1437–43. https://doi.org/10.1183/09031936.00173410.CrossRefPubMed

32.

Serra G, Milito C, Mitrevski M, Granata G, Martini H, Pesce AM, et al. Lung MRI as a possible alternative to CT scan for patients with primary immune deficiencies and increased radiosensitivity. Chest. 2011;140(6):1581–9. https://doi.org/10.1378/chest.10-3147.CrossRefPubMed

33.

van de Ven AA, van Montfrans JM, Terheggen-Lagro SW, Beek FJ, Hoytema van Konijnenburg DP, Kessels OA, et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest. 2010;138(2):371–9. https://doi.org/10.1378/chest.09-2398.CrossRefPubMed

34.

Pereira FF, Ibiapina Cda C, Alvim CG, Camargos PA, Figueiredo R, Pedrosa JF. Correlation between Bhalla score and spirometry in children and adolescents with cystic fibrosis. Rev Assoc Med Bras (1992). 2014;60(3):216–21.CrossRef

35.

Standardization of spirometry--1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987;136(5):1285–98. https://doi.org/10.1164/ajrccm/136.5.1285.

36.

Polgar G, Promadhat V. Pulmonary function testing in children : techniques and standards. Philadelphia: Saunders; 1971.

37.

Cabral-Marques O, Klaver S, Schimke LF, Ascendino EH, Khan TA, Pereira PV, et al. First report of the hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes. J Clin Immunol. 2014;34(2):146–56. https://doi.org/10.1007/s10875-013-9980-4.CrossRefPubMed

38.

Lougaris V, Badolato R, Ferrari S, Plebani A. Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features. Immunol Rev. 2005;203:48–66. https://doi.org/10.1111/j.0105-2896.2005.00229.x.CrossRefPubMed

39.

Lopes AJ, Camilo GB, de Menezes SL, Guimaraes FS. Impact of different etiologies of bronchiectasis on the pulmonary function tests. Clin Med Res. 2015;13(1):12–9. https://doi.org/10.3121/cmr.2014.1236.CrossRefPubMedPubMedCentral

40.

Feydy A, Sibilia J, De Kerviler E, Zagdanski AM, Chevret S, Fermand JP, et al. Chest high resolution CT in adults with primary humoral immunodeficiency. Br J Radiol. 1996;69(828):1108–16. https://doi.org/10.1259/0007-1285-69-828-1108.CrossRefPubMed

41.

Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr. 2014;2:77. https://doi.org/10.3389/fped.2014.00077.CrossRefPubMedPubMedCentral

42.

de Miranda NF, Bjorkman A, Pan-Hammarstrom Q. DNA repair: the link between primary immunodeficiency and cancer. Ann N Y Acad Sci. 2011;1246:50–63. https://doi.org/10.1111/j.1749-6632.2011.06322.x.CrossRefPubMed

43.

Yazdani R, Abolhassani H, Asgardoon M, Shaghaghi M, Modaresi M, Azizi G, et al. Infectious and noninfectious pulmonary complications in patients with primary immunodeficiency disorders. J Investig Allergol Clin Immunol. 2017;27(4):213–24. https://doi.org/10.18176/jiaci.0166.CrossRefPubMed

44.

Howard V, Greene JM, Pahwa S, Winkelstein JA, Boyle JM, Kocak M, et al. The health status and quality of life of adults with X-linked agammaglobulinemia. Clin Immunol (Orlando, Fla). 2006;118(2-3):201–8. https://doi.org/10.1016/j.clim.2005.11.002.CrossRef

45.

Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7. https://doi.org/10.1182/blood-2011-09-377945.CrossRefPubMedPubMedCentral

46.

Brower KS, Del Vecchio MT, Aronoff SC. The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects. BMC Pediatr. 2014;14:4. https://doi.org/10.1186/s12887-014-0299-y.CrossRefPubMedPubMedCentral

47.

Haidopoulou K, Calder A, Jones A, Jaffe A, Sonnappa S. Bronchiectasis secondary to primary immunodeficiency in children: longitudinal changes in structure and function. Pediatr Pulmonol. 2009;44(7):669–75. https://doi.org/10.1002/ppul.21036.CrossRefPubMed

48.

Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, et al. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007;149(3):410–23. https://doi.org/10.1111/j.1365-2249.2007.03432.x.CrossRefPubMedPubMedCentral

49.

Quartier P, Debre M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999;134(5):589–96.CrossRef

50.

Tarzi MD, Grigoriadou S, Carr SB, Kuitert LM, Longhurst HJ. Clinical immunology review series: an approach to the management of pulmonary disease in primary antibody deficiency. Clin Exp Immunol. 2009;155(2):147–55. https://doi.org/10.1111/j.1365-2249.2008.03851.x.CrossRefPubMedPubMedCentral

51.

Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W. Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001;2(3):223–8. https://doi.org/10.1038/85277.CrossRefPubMed

52.

Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, et al. Comparison of common monogenic defects in a large predominantly antibody deficiency cohort. J Allergy Clin Immunol Pract. 2018. https://doi.org/10.1016/j.jaip.2018.09.004.

Titel: Respiratory Complications in Patients with Hyper IgM Syndrome
Publikationsdatum: 11.06.2019
Erschienen in: Journal of Clinical Immunology / Ausgabe 6/2019
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-019-00650-3

Kompaktes Leitlinien-Wissen Innere Medizin

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

IG-Nobelpreis 2024: Von analer Atmung und hemisphärischen Haarwirbeln

13.09.2024 Panorama Nachrichten

Der Ig-Nobelpreis feiert Forschung, die erst zum Lachen und dann zum Nachdenken einlädt. Arbeiten mit Medizinbezug konnten in diesem Jahr vier der zehn Preise abräumen. Dabei war von unauffindbaren Hundertjährigen bis zur enteralen Beatmung einiges geboten, was dem Leitgedanken des Preises gerecht wird.

Schwere Aortenstenose: „Klappenersatz sollte unabhängig von Symptomen erfolgen“

12.09.2024 Aortenklappenstenose Nachrichten

Soll Menschen mit schwerer Aortenstenose und normaler linksventrikulärer Ejektionsfraktion auch dann zum Klappenersatz geraten werden, wenn sie nachweislich symptomfrei sind? Die AVATAR-Studie und die jetzt publizierten Langzeitdaten sprechen klar dafür.

Hitze lässt kardiale und pulmonale Mortalität steigen

12.09.2024 Hitzebelastung Nachrichten

Mit steigenden Temperaturen nehmen Todesfälle durch Herz- und Lungenerkrankungen zu, das belegt eine Querschnittstudie aus Deutschland. Die Daten legen offen, welche Personengruppen besonders gefährdet sind.

Kombination Doxorubicin-Trabectedin erhöht die Chancen

12.09.2024 Weichteilsarkome Nachrichten

Doxorubicin ist ein Standardmedikament in der Behandlung von Patientinnen und Patienten mit Leiomyosarkomen. In einer Studie hat eine französische Forschungsgruppe geprüft, ob die Zugabe von Trabectedin die Überlebenschancen verbessert.

EKG Essentials: EKG befunden mit System

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Jetzt 10 CME-Punkte sammeln

Update Innere Medizin

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

Newsletter bestellen

Live-Webinar "Das Impf-Update für Ihre Praxis – RSV, Pneumokokken, Grippe und Covid"

Springer Medizin

Respiratory Complications in Patients with Hyper IgM Syndrome

Abstract

Purpose

Methods

Results

Conclusions

Kompaktes Leitlinien-Wissen Innere Medizin

Neu im Fachgebiet Innere Medizin

IG-Nobelpreis 2024: Von analer Atmung und hemisphärischen Haarwirbeln

Schwere Aortenstenose: „Klappenersatz sollte unabhängig von Symptomen erfolgen“

Hitze lässt kardiale und pulmonale Mortalität steigen

Kombination Doxorubicin-Trabectedin erhöht die Chancen

EKG Essentials: EKG befunden mit System

Update Innere Medizin

Live-Webinar "Das Impf-Update für Ihre Praxis – RSV, Pneumokokken, Grippe und Covid"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2019

RNASEH2B Related Adult-Onset Interferonopathy

Cellular Defects in CVID Patients with Chronic Lung Disease in the USIDNET Registry

Prof. Dr. Beatriz Tavares Costa-Carvalho Obituary

Myriad Faces of Chronic Granulomatous Disease: All in an Indian Family with Novel CYBB Defect

WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure

Chronic Mucocutaneous Candidiasis in an Adolescent Boy Due to a Novel Mutation in TRAF3IP2

Kompaktes Leitlinien-Wissen Innere Medizin

IG-Nobelpreis 2024: Von analer Atmung und hemisphärischen Haarwirbeln

Schwere Aortenstenose: „Klappenersatz sollte unabhängig von Symptomen erfolgen“

Hitze lässt kardiale und pulmonale Mortalität steigen

Kombination Doxorubicin-Trabectedin erhöht die Chancen

EKG Essentials: EKG befunden mit System

Update Innere Medizin