Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology

V. Lougaris; A. Soresina; M. Baronio; D. Montin; S. Martino; S. Signa; S. Volpi; M. Zecca; M. Marinoni; L.A. Baselli; R.M. Dellepiane; M. Carrabba; G. Fabio; M.C. Putti; F. Cinetto; C. Lunardi; L. Gazzurelli; A. Benvenuto; P. Bertolini; F. Conti; R. Consolini; S. Ricci; C. Azzari; L. Leonardi; M. Duse; F. Pulvirenti; C. Milito; I. Quinti; C. Cancrini; A. Finocchi; V. Moschese; E. Cirillo; L. Crescenzi; G. Spadaro; C. Marasco; A. Vacca; F. Cardinale; B. Martire; A. Trizzino; M. Licciardello; F. Cossu; G. Di Matteo; R. Badolato; S. Ferrari; S. Giliani; A. Pession; A. Ugazio; C. Pignata; A. Plebani

doi:10.1016/j.jaci.2020.03.001

Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology

V. Lougaris, A. Soresina, M. Baronio, D. Montin, S. Martino, S. Signa, S. Volpi, M. Zecca, M. Marinoni, L.A. Baselli, R.M. Dellepiane, M. Carrabba, G. Fabio, M.C. Putti, F. Cinetto, C. Lunardi, L. Gazzurelli, A. Benvenuto, P. Bertolini, F. ContiR. Consolini, S. Ricci, C. Azzari, L. Leonardi, M. Duse, F. Pulvirenti, C. Milito, I. Quinti, C. Cancrini, A. Finocchi, V. Moschese, E. Cirillo, L. Crescenzi, G. Spadaro, C. Marasco, A. Vacca, F. Cardinale, B. Martire, A. Trizzino, M. Licciardello, F. Cossu, G. Di Matteo, R. Badolato, S. Ferrari, S. Giliani, A. Pession, A. Ugazio, C. Pignata, A. Plebani

Research output: Contribution to journal › Article › peer-review

Abstract

Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective: Our aim was to describe the natural history of XLA. Methods: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients’ laboratory, clinical, and imaging data were recorded on an annual base. Results: Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. Conclusions: This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients’ clinical management and increase awareness among physicians.

Original language	English
Pages (from-to)	429-437
Number of pages	9
Journal	J. Allergy Clin. Immunol.
Volume	146
Issue number	2
DOIs	https://doi.org/10.1016/j.jaci.2020.03.001
Publication status	Published - Aug 2020

Keywords

Bruton tyrosine kinase
chronic lung disease
X-linked agammaglobulinemia

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10.1016/j.jaci.2020.03.001

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082707318&doi=10.1016%2fj.jaci.2020.03.001&partnerID=40&md5=e216ba8210924c9b24ce41841ce54174

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Lougaris, V., Soresina, A., Baronio, M., Montin, D., Martino, S., Signa, S., Volpi, S., Zecca, M., Marinoni, M., Baselli, L. A., Dellepiane, R. M., Carrabba, M., Fabio, G., Putti, M. C., Cinetto, F., Lunardi, C., Gazzurelli, L., Benvenuto, A., Bertolini, P., ... Plebani, A. (2020). Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology. J. Allergy Clin. Immunol., 146(2), 429-437. https://doi.org/10.1016/j.jaci.2020.03.001

Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality : Journal of Allergy and Clinical Immunology. / Lougaris, V.; Soresina, A.; Baronio, M.; Montin, D.; Martino, S.; Signa, S.; Volpi, S.; Zecca, M.; Marinoni, M.; Baselli, L.A.; Dellepiane, R.M.; Carrabba, M.; Fabio, G.; Putti, M.C.; Cinetto, F.; Lunardi, C.; Gazzurelli, L.; Benvenuto, A.; Bertolini, P.; Conti, F.; Consolini, R.; Ricci, S.; Azzari, C.; Leonardi, L.; Duse, M.; Pulvirenti, F.; Milito, C.; Quinti, I.; Cancrini, C.; Finocchi, A.; Moschese, V.; Cirillo, E.; Crescenzi, L.; Spadaro, G.; Marasco, C.; Vacca, A.; Cardinale, F.; Martire, B.; Trizzino, A.; Licciardello, M.; Cossu, F.; Di Matteo, G.; Badolato, R.; Ferrari, S.; Giliani, S.; Pession, A.; Ugazio, A.; Pignata, C.; Plebani, A.

In: J. Allergy Clin. Immunol., Vol. 146, No. 2, 08.2020, p. 429-437.

Research output: Contribution to journal › Article › peer-review

Lougaris, V, Soresina, A, Baronio, M, Montin, D, Martino, S, Signa, S, Volpi, S , Zecca, M, Marinoni, M, Baselli, LA, Dellepiane, RM , Carrabba, M, Fabio, G, Putti, MC, Cinetto, F, Lunardi, C, Gazzurelli, L, Benvenuto, A, Bertolini, P, Conti, F, Consolini, R, Ricci, S, Azzari, C, Leonardi, L, Duse, M, Pulvirenti, F, Milito, C, Quinti, I, Cancrini, C, Finocchi, A, Moschese, V, Cirillo, E, Crescenzi, L, Spadaro, G, Marasco, C, Vacca, A, Cardinale, F, Martire, B, Trizzino, A, Licciardello, M, Cossu, F, Di Matteo, G, Badolato, R, Ferrari, S, Giliani, S, Pession, A, Ugazio, A, Pignata, C & Plebani, A 2020, 'Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology', J. Allergy Clin. Immunol., vol. 146, no. 2, pp. 429-437. https://doi.org/10.1016/j.jaci.2020.03.001

Lougaris, V. ; Soresina, A. ; Baronio, M. ; Montin, D. ; Martino, S. ; Signa, S. ; Volpi, S. ; Zecca, M. ; Marinoni, M. ; Baselli, L.A. ; Dellepiane, R.M. ; Carrabba, M. ; Fabio, G. ; Putti, M.C. ; Cinetto, F. ; Lunardi, C. ; Gazzurelli, L. ; Benvenuto, A. ; Bertolini, P. ; Conti, F. ; Consolini, R. ; Ricci, S. ; Azzari, C. ; Leonardi, L. ; Duse, M. ; Pulvirenti, F. ; Milito, C. ; Quinti, I. ; Cancrini, C. ; Finocchi, A. ; Moschese, V. ; Cirillo, E. ; Crescenzi, L. ; Spadaro, G. ; Marasco, C. ; Vacca, A. ; Cardinale, F. ; Martire, B. ; Trizzino, A. ; Licciardello, M. ; Cossu, F. ; Di Matteo, G. ; Badolato, R. ; Ferrari, S. ; Giliani, S. ; Pession, A. ; Ugazio, A. ; Pignata, C. ; Plebani, A. / Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality : Journal of Allergy and Clinical Immunology. In: J. Allergy Clin. Immunol. 2020 ; Vol. 146, No. 2. pp. 429-437.

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title = "Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology",

abstract = "Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective: Our aim was to describe the natural history of XLA. Methods: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients{\textquoteright} laboratory, clinical, and imaging data were recorded on an annual base. Results: Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. Conclusions: This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients{\textquoteright} clinical management and increase awareness among physicians.",

keywords = "Bruton tyrosine kinase, chronic lung disease, X-linked agammaglobulinemia",

author = "V. Lougaris and A. Soresina and M. Baronio and D. Montin and S. Martino and S. Signa and S. Volpi and M. Zecca and M. Marinoni and L.A. Baselli and R.M. Dellepiane and M. Carrabba and G. Fabio and M.C. Putti and F. Cinetto and C. Lunardi and L. Gazzurelli and A. Benvenuto and P. Bertolini and F. Conti and R. Consolini and S. Ricci and C. Azzari and L. Leonardi and M. Duse and F. Pulvirenti and C. Milito and I. Quinti and C. Cancrini and A. Finocchi and V. Moschese and E. Cirillo and L. Crescenzi and G. Spadaro and C. Marasco and A. Vacca and F. Cardinale and B. Martire and A. Trizzino and M. Licciardello and F. Cossu and {Di Matteo}, G. and R. Badolato and S. Ferrari and S. Giliani and A. Pession and A. Ugazio and C. Pignata and A. Plebani",

note = "Export Date: 10 August 2020 CODEN: JACIB Correspondence Address: Lougaris, V.; Pediatrics Clinic and Institute of Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Pediatrics Clinic and Institute of Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Piazzale Spedali Civili 1, Italy; email: vlougarisbs@yahoo.com",

year = "2020",

month = aug,

doi = "10.1016/j.jaci.2020.03.001",

language = "English",

volume = "146",

pages = "429--437",

journal = "J. Allergy Clin. Immunol.",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "2",

}

TY - JOUR

T1 - Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality

T2 - Journal of Allergy and Clinical Immunology

AU - Lougaris, V.

AU - Soresina, A.

AU - Baronio, M.

AU - Montin, D.

AU - Martino, S.

AU - Signa, S.

AU - Volpi, S.

AU - Zecca, M.

AU - Marinoni, M.

AU - Baselli, L.A.

AU - Dellepiane, R.M.

AU - Carrabba, M.

AU - Fabio, G.

AU - Putti, M.C.

AU - Cinetto, F.

AU - Lunardi, C.

AU - Gazzurelli, L.

AU - Benvenuto, A.

AU - Bertolini, P.

AU - Conti, F.

AU - Consolini, R.

AU - Ricci, S.

AU - Azzari, C.

AU - Leonardi, L.

AU - Duse, M.

AU - Pulvirenti, F.

AU - Milito, C.

AU - Quinti, I.

AU - Cancrini, C.

AU - Finocchi, A.

AU - Moschese, V.

AU - Cirillo, E.

AU - Crescenzi, L.

AU - Spadaro, G.

AU - Marasco, C.

AU - Vacca, A.

AU - Cardinale, F.

AU - Martire, B.

AU - Trizzino, A.

AU - Licciardello, M.

AU - Cossu, F.

AU - Di Matteo, G.

AU - Badolato, R.

AU - Ferrari, S.

AU - Giliani, S.

AU - Pession, A.

AU - Ugazio, A.

AU - Pignata, C.

AU - Plebani, A.

N1 - Export Date: 10 August 2020 CODEN: JACIB Correspondence Address: Lougaris, V.; Pediatrics Clinic and Institute of Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Pediatrics Clinic and Institute of Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Piazzale Spedali Civili 1, Italy; email: vlougarisbs@yahoo.com

PY - 2020/8

Y1 - 2020/8

N2 - Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective: Our aim was to describe the natural history of XLA. Methods: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients’ laboratory, clinical, and imaging data were recorded on an annual base. Results: Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. Conclusions: This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients’ clinical management and increase awareness among physicians.

AB - Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. Objective: Our aim was to describe the natural history of XLA. Methods: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients’ laboratory, clinical, and imaging data were recorded on an annual base. Results: Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. Conclusions: This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients’ clinical management and increase awareness among physicians.

KW - Bruton tyrosine kinase

KW - chronic lung disease

KW - X-linked agammaglobulinemia

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Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality: Journal of Allergy and Clinical Immunology

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Keywords

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