Chronic granulomatous disease 2018: advances in pathophysiology and clinical management
Abstract
Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and to resolve inflammation. The last few years have witnessed major advances in pathogenesis and clinical management of the disease:
1.
Better understanding of 3 physiologic anti-inflammatory functions of NADPH oxidase-derived reactive oxygen species: Promotion of the clearance of dying host cells, suppression of inflammasomes, and regulation of type I interferon signalling. This insight is opening new avenues for targeted drug interventions.
2.
Advances in reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell transplantation (HSCT) make it a promising and safe procedure even for fragile patients with ongoing severe infection or hyperinflammation.
3.
Encouraging early data of a multicenter trial of gene-replacement therapy using a self-inactivated lentiviral vector.
Combining targeted anti-infectious/anti-inflammatory measures and considering extended indications for curative HSCT are key to improving patient outcome further. Gene therapy will likely become a viable option for disease correction, but long-term assessment is not yet possible.
Statement of novelty: We discuss important advances in pathogenesis and treatment of CGD that will change our approach to clinical management.
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REFERENCES
Åhlin A., Fugeläng J., de Boer M., Ringden O., Fasth A., and Winiarski J. 2013. Chronic granulomatous disease—Haematopoietic stem cell transplantation versus conventional treatment. Acta Paediatr. 102:1087–1094.
Arnadottir G.A., Norddahl G.L., Gudmundsdottir S., Agustsdottir A.B., Sigurdsson S., Jensson B.O., Bjarnadottir K., Theodors F., Benonisdottir S., Ivarsdottir E.V., Oddsson A., Kristjansson R.P., Sulem G., Alexandersson K.F., Juliusdottir T., Gudmundsson K.R., Saemundsdottir J., Jonasdottir A., Jonasdottir A., Sigurdsson A., Manzanillo P., Gudjonsson S.A., Thorisson G.A., Magnusson O.Th., Masson G., Orvar K.B., Holm H., Bjornsson S., Arngrimsson R., Gudbjartsson D.F., Thorsteinsdottir U., Jonsdottir I., Haraldsson A., Sulem P., and Stefansson K. 2018. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes CGD. Nat. Commun. 9:4447.
Bagaitkar J., Huang J., Zeng M.Y., Pech N.K., Monlish D.A., Perez-Zapata L.J., Miralda I., Schuettpelz L.G., and Dinauer M.C. 2018. NADPH oxidase activation regulates apoptotic neutrophil clearance by murine macrophages. Blood. 131:2367–2378.
Bartelink I.H., Boelens J.J., Bredius R.G., Egberts A.C., Wang C., Bierings M.B., Shaw P.J., Nath C.E., Hempel G., Zwaveling J., Danhof M., and Knibbe C.A. 2012. Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: Towards individualized dosing. Clin. Pharmacokinet. 51:331–345.
Bianchi M., Niemiec M.J., Siler U., Urban C.F., and Reichenbach J. 2011. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J. Allergy Clin. Immunol. 127:1243–1252.e7.
Cole T., Pearce M.S., Cant A.J., Cale C.M., Goldblatt D., and Gennery A.R. 2013. Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation. J. Allergy Clin. Immunol. 132:1150–1155.
Conti F., Lugo-Reyes S.O., Blancas Galicia L., He J., Aksu G., Borges de Oliveira E. Jr., Deswarte C., Hubeau M., Karaca N., de Suremain M., Guérin A., Baba L.A., Prando C., Guerrero G.G., Emiroglu M., Öz F.N., Yamazaki Nakashimada M.A., Gonzalez Serrano E., Espinosa S., Barlan I., Pérez N., Regairaz L., Guidos Morales H.E., Bezrodnik L., Di Giovanni D., Dbaibo G., Ailal F., Galicchio M., Oleastro M., Chemli J., Danielian S., Perez L., Ortega M.C., Soto Lavin S., Hertecant J., Anal O., Kechout N., Al-Idrissi E., ElGhazali G., Bondarenko A., Chernyshova L., Ciznar P., Herbigneaux R.M., Diabate A., Ndaga S., Konte B., Czarna A., Migaud M., Pedraza-Sánchez S., Zaidi M.B., Vogt G., Blanche S., Benmustapha I., Mansouri D., Abel L., Boisson-Dupuis S., Mahlaoui N., Bousfiha A.A., Picard C., Barbouche R., Al-Muhsen S., Espinosa-Rosales F.J., Kütükçüler N., Condino-Neto A., Casanova J.L., and Bustamante J. 2016. Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases. J. Allergy Clin. Immunol. 138:241–248.e3.
Dunogué B., Pilmis B., Mahlaoui N., Elie C., Coignard-Biehler H., Amazzough K., Noël N., Salvator H., Catherinot E., Couderc L.J., Sokol H., Lanternier F., Fouyssac F., Bardet J., Bustamante J., Gougerot-Pocidalo M.A., Barlogis V., Masseau A., Durieu I., Lecuit M., Suarez F., Fischer A., Blanche S., Hermine O., and Lortholary O. 2017. Chronic granulomatous disease in patients reaching adulthood: A nationwide study in France. Clin. Infect. Dis. 64:767–775.
Fernandez-Boyanapalli R.F., Falcone E.L., Zerbe C.S., Marciano B.E., Frasch S.C., Henson P.M., Holland S.M., and Bratton D.L. 2015a. Impaired efferocytosis in human chronic granulomatous disease is reversed by pioglitazone treatment. J. Allergy Clin. Immunol. 136:1399–1401.e3.
Fernandez-Boyanapalli R.F., Frasch S.C., Thomas S.M., Malcolm K.C., Nicks M., Harbeck R.J., Jakubzick C.V., Nemenoff R., Henson P.M., Holland S.M., and Bratton D.L. 2015b. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease. J. Allergy Clin. Immunol. 135:517–527.e12.
Freeman A.F., Marciano B.E., Anderson V.L., Uzel G., Costas C., and Holland S.M. 2011. Corticosteroids in the treatment of severe nocardia pneumonia in chronic granulomatous disease. Pediatr. Infect. Dis. J. 30:806–808.
Fuchs T.A., Abed U., Goosmann C., Hurwitz R., Schulze I., Wahn V., Weinrauch Y., Brinkmann V., and Zychlinsky A. 2007. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol. 176:231–241.
Gallin J.I., Alling D.W., Malech H.L., Wesley R., Koziol D., Marciano B., Eisenstein E.M., Turner M.L., DeCarlo E.S., Starling J.M., and Holland S.M. 2003. Itraconazole to prevent fungal infections in chronic granulomatous disease. N. Engl. J. Med. 348:2416–2422.
Güngör T., Teira P., Slatter M., Stussi G., Stepensky P., Moshous D., Vermont C., Ahmad I., Shaw P.J., Telles da Cunha J.M., Schlegel P.G., Hough R., Fasth A., Kentouche K., Gruhn B., Fernandes J.F., Lachance S., Bredius R., Resnick I.B., Belohradsky B.H., Gennery A., Fischer A., Gaspar H.B., Schanz U., Seger R., Rentsch K., Veys P., Haddad E., Albert M.H., Hassan M., and Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. 2014. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: A prospective multicentre study. Lancet. 383:436–448.
Hahn K.J., Ho N., Yockey L., Kreuzberg S., Daub J., Rump A., Marciano B.E., Quezado M., Malech H.L., Holland S.M., Heller T., and Zerbe C.S. 2015. Treatment with anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Am. J. Gastroenterol. 110:938–939.
Heckmann B.L., Boada-Romero E., Cunha L.D., Magne J., and Green D.R. 2017. LC3-associated phagocytosis and inflammation. J. Mol. Biol. 429:3561–3576.
Henriet S.S.V., Verweij P.E., and Warris A. 2012. Aspergillus nidulans and chronic granulomatous disease: A unique host–pathogen interaction. J. Infect. Dis. 206:1128–1137.
Holmdahl R., Sareila O., Olsson L.M., Bäckdahl L., and Wing K. 2016. Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. Immunol. Rev. 269:228–247.
Hussain N., Feld J.J., Kleiner D.E., Hoofnagle J.H., Garcia-Eulate R., Ahlawat S., Koziel D.E., Anderson V., Hilligoss D., Choyke P., Gallin J.I., Liang T.J., Malech H.L., Holland S.M., and Heller T. 2007. Hepatic abnormalities in patients with chronic granulomatous disease. Hepatology. 45:675–683.
Jung H.H., Danek A., and Frey B.M. 2007. McLeod syndrome: A neurohaematological disorder. Vox Sang. 93:112–121.
Keller M.D., Notarangelo L.D., and Malech H.L. 2018. Future of care for patients with chronic granulomatous disease: Gene therapy and targeted molecular medicine. J. Pediatric Infect. Dis. Soc. 7(Suppl 1):S40–S44.
Kuhns D.B., Alvord W.G., Heller T., Feld J.J., Pike K.M., Marciano B.E., Uzel G., DeRavin S.S., Priel D.A., Soule B.P., Zarember K.A., Malech H.L., Holland S.M., and Gallin J.I. 2010. Residual NADPH oxidase and survival in chronic granulomatous disease. N. Engl. J. Med. 363:2600–2610.
Lee, P.P., and Lau, Y.L. 2017. Endemic infections in chronic granulomatous disease. In Chronic granulomatous disease: Genetics, biology and clinical management. Edited by R.A. Seger, D. Roos, B.H. Segal, and T.W. Kuijpers. New York, NY, USA: Nova Biomedical Press. pp. 125–162.
Lee P.P., Chan K.W., Jiang L., Chen T., Li C., Lee T.L., Mak P.H., Fok S.F., Yang X., and Lau Y.L. 2008. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: A review of 17 patients living in a region endemic for tuberculosis. Pediatr. Infect. Dis. J. 27:224–230.
Leiding, J.W., and Holland, S.M. 2016. Chronic granulomatous disease. In GeneReviews® [Internet]. Edited by M.P. Adam, H.H. Ardinger, R.A. Pagon, S.E. Wallace, L.J.H. Bean, K. Stephens, and A. Amemiya. Seattle, WA, USA: University of Washington.
Luznik L., Jones R.J., and Fuchs E.J. 2010. High-dose cyclophosphamide for graft-versus-host disease prevention. Curr. Opin. Hematol. 17:493–499.
Magnani A. and Mahlaoui N. 2016. Managing inflammatory manifestations in patients with chronic granulomatous disease. Pediatr. Drugs. 18:335–345.
Maltesen H.R., Nielsen C.H., Dalbøge C.S., and Baslund B. 2010. Methylprednisolone prevents tumour necrosis factor-α-dependent multinucleated giant cell formation. Rheumatology. 49:2037–2042.
Marciano B.E., Rosenzweig S.D., Kleiner D.E., Anderson V.L., Darnell D.N., Anaya-O’Brien S., Hilligoss D.M., Malech H.L., Gallin J.I., and Holland S.M. 2004. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 114:462–468.
Marciano B.E., Zerbe C.S., Falcone E.L., Ding L., DeRavin S.S., Daub J., Kreuzburg S., Yockey L., Hunsberger S., Foruraghi L., Barnhart L.A., Matharu K., Anderson V., Darnell D.N., Frein C., Fink D.L., Lau K.P., Long Priel D.A., Gallin J.I., Malech H.L., Uzel G., Freeman A.F., Kuhns D.B., Rosenzweig S.D., and Holland S.M. 2018. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J. Allergy Clin. Immunol. 141:365–371.
Margolis D.M., Melnick D.A., Alling D.W., and Gallin J.I. 1990. Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease. J. Infect. Dis. 162:723–726.
Martín A., Marques L., Soler-Palacín P., Caragol I., Hernandez M., Figueras C., and Español T. 2009. Visceral leishmaniasis associated hemophagocytic syndrome in patients with chronic granulomatous disease. Pediatr. Infect. Dis. 28:753–754.
Martire B., Rondelli R., Soresina A., Pignata C., Broccoletti T., Finocchi A., Rossi P., Gattorno M., Rabusin M., Azzari C., Dellepiane R.M., Pietrogrande M.C., Trizzino A., Di Bartolomeo P., Martino S., Carpino L., Cossu F., Locatelli F., Maccario R., Pierani P., Putti M.C., Stabile A., Notarangelo L.D., Ugazio A.G., Plebani A., De Mattia D., and IPINET. 2008. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: An Italian multicenter study. Clin. Immunol. 126:155–164.
Maschan M., Blagov S, Shelikhova L., Shekhovtsova Z., Balashov D., Starichkova J., Kurnikova E., Boyakova E., Muzalevskii Y., Kazachenok A., Trakhtman P., Osipova E., Khripkova N., Zhogov V., Novichkova G., and Maschan A. 2018. Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: Results of a pilot trial. Bone Marrow Transplant. 53:264–273.
Matsura T. 2014. Oxidized phosphatidylserine: Production and bioactivities. Yonago Acta Med. 57:119–127.
Migliavacca M., Assanelli A., Ferrua F., Cicalese M.P., Biffi A., Frittoli M., Silvani P., Chidini G., Calderini E., Mandelli A., Camporesi A., Milani R., Farinelli G., Nicoletti R., Ciceri F., Aiuti A., and Bernardo M.E. 2016. Pioglitazone as a novel therapeutic approach in chronic granulomatous disease. J. Allergy Clin. Immunol. 137:1913–1915.e2.
Morillo-Gutierrez B., Beier R., Rao K., Burroughs L., Schulz A., Ewins A.M., Gibson B., Sedlacek P., Krol L., Strahm B., Zaidman I., Kalwak K., Talano J.A., Woolfrey A., Fraser C., Meyts I., Müller I., Wachowiak J., Bernardo M.E., Veys P., Sykora K.W., Gennery A.R., and Slatter M. 2016. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter experience. Blood. 128:440–448.
Nakazawa Y., Kawai T., Arai K., Tamura E., Uchiyama T., and Onodera M. 2017. Fecal calprotectin rise in chronic granulomatous disease-associated colitis. J. Clin. Immunol. 37:741–743.
Noel N., Mahlaoui N., Blanche S., Suarez F., Coignard-Biehler H., Durieu I., Godeberge P., Sokol H, Catherinot E., Poiree S., Chapdelaine H., Dunogue B., Bodemer C., Lecuit M., Fischer A., Lortholary O., and Hermine O. 2013. Efficacy and safety of thalidomide in patients with inflammatory manifestations of chronic granulomatous disease: A retrospective case series. J. Allergy Clin. Immunol. 132:997–1000.e4.
Parta M., Hilligoss D., Kelly C., Kwatemaa N., Theobald N., Malech H., and Kang E.M. 2015. Haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with chronic granulomatous disease and active infection: A first report. J. Clin. Immunol. 35:675–680.
Reeves E.P., Lu H., Jacobs H.L., Messina C.G., Bolsover S., Gabella G., Potma E.O., Warley A., Roes J., and Segal A.W. 2002. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature. 416:291–297.
Regueiro-García A., Fariña-Nogueira S., Porto-Arceo J.Á., and Couselo-Sánchez J.M. 2018. Haploidentical stem cell transplantation in a boy with chronic granulomatous disease. Allergol. Immunopathol. 46:385–388.
Roos, D., Tool, A.T.J., van Leeuwen, K., and de Boer, M. 2017. Biochemical and genetic diagnosis of chronic granulomatous disease. In Chronic granulomatous disease: Genetics, biology and clinical management. Edited by R.A. Seger, D. Roos, B.H. Segal, and T.W. Kuijpers. New York, NY, USA: Nova Biomedical Press. pp. 231–300.
Sanford A.N., Suriano A.R., Herche D., Dietzmann K., and Sullivan K.E. 2006. Abnormal apoptosis in chronic granulomatous disease and autoantibody production characteristic of lupus. Rheumatology. 45:178–181.
Santilli G., Almarza E., Brendel C., Choi U., Beilin C., Blundell M.P., Haria S., Parsley K.L., Kinnon C., Malech H.L., Bueren J.A., Grez M., and Thrasher A.J. 2011. Biochemical correction of X-CGD by a novel chimeric promoter regulating high levels of transgene expression in myeloid cells. Mol. Ther. 19:122–132.
Seger R.A. 2010. Hematopoietic stem cell transplantation for chronic granulomatous disease. Immunol. Allergy Clin. North Am. 30:195–208.
Seger, R.A., Roos, D., Segal, B.H., and Kuijpers, T.W. (Editors). 2017. Chronic granulomatous disease: Genetics, biology, clinical management [Internet]. New York, NY, USA: Nova Publishers.
Shah R.M., Elfeky R., Nademi Z., Qasim W., Amrolia P., Chiesa R., Rao K., Lucchini G., Silva J.M.F., Worth A., Barge D., Ryan D., Conn J., Cant A.J., Skinner R., Abd Hamid I.J., Flood T., Abinun M., Hambleton S., Gennery A.R., Veys P., and Slatter M. 2018. T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. J. Allergy Clin. Immunol. 141:1417–1426.e1.
Siddiqui S., Anderson V.L., Hilligoss D.M., Abinun M., Kuijpers T.W., Masur H., Witebsky F.G., Shea Y.R., Gallin J.I., Malech H.L., and Holland S.M. 2007. Fulminant mulch pneumonitis: An emergency presentation of chronic granulomatous disease. Clin. Infect. Dis. 45:673–681.
Sirinavin S., Techasaensiri C., Benjaponpitak S., Pornkul R., and Vorachit M. 2005. Invasive Chromobacterium violaceum infection in children: Case report and review. Pediatr. Infect. Dis. J. 24:559–561.
Sollberger G., Tilley D.O., and Zychlinsky A. 2018. Neutrophil extracellular traps: The biology of chromatin externalization. Dev. Cell. 44:542–553.
Stein S., Ott M.G., Schultze-Strasser S., Jauch A., Burwinkel B., Kinner A., Schmidt M., Krämer A., Schwäble J., Glimm H., Koehl U., Preiss C., Ball C., Martin H., Göhring G., Schwarzwaelder K., Hofmann W.K., Karakaya K., Tchatchou S., Yang R., Reinecke P., Kühlcke K., Schlegelberger B., Thrasher A.J., Hoelzer D., Seger R., von Kalle C., and Grez M. 2010. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat. Med. 16:198–204.
Straughan D.M., McLoughlin K.C., Mullinax J.E., Marciano B.E., Freeman A.F., Anderson V.L., Uzel G., Azoury S.C., Sorber R., Quadri H.S., Malech H.L., DeRavin S.S., Kamal N., Koh C., Zerbe C.S., Kuhns DB, Gallin J.I., Heller T., Holland S.M., and Rudloff U. 2018. The changing paradigm of management of liver abscesses in chronic granulomatous disease. Clin. Infect. Dis. 66:1427–1434.
The International Chronic Granulomatous Disease Cooperative Study Group. 1991. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N. Engl. J. Med. 324:509–516.
Thomas D.C. 2017. The phagocyte respiratory burst: Historical perspectives and recent advances. Immunol. Lett. 192:88–96.
Thomas D.C., Clare S., Sowerby J.M., Pardo M., Juss J.K., Goulding D.A., van der Weyden L., Storisteanu D., Prakash A., Espéli M., Flint S., Lee J.C., Hoenderdos K., Kane L., Harcourt K., Mukhopadhyay S., Umrania Y., Antrobus R., Nathan J.A., Adams D.J., Bateman A., Choudhary J.S., Lyons P.A., Condliffe A.M., Chilvers E.R., Dougan G., and Smith K.G. 2017. Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity. J. Exp. Med. 214:1111–1128.
Thomas D.C., Charbonnier L.M., Schejtman A., Aldhekri H., Coomber E.L., Dufficy E.R., Beenken A.E., Lee J.C., Clare S., Speak A.O., Thrasher A.J., Santilli G., Al-Mousa H., Alkuraya F.S., Chatila T.A., and Smith K.G.C. 2019. EROS/CYBC1 mutations: Decreased NADPH oxidase function and chronic granulomatous disease. J. Allergy Clin. Immunol. 143:782–785.
Thomsen I.P., Smith M.A., Holland S.M., and Creech C.B. 2016. A comprehensive approach to the management of children and adults with chronic granulomatous disease. J. Allergy Clin. Immunol. Pract. 4:1082–1088.
Thrasher, A. 2018. Gene therapy for X-linked chronic granulomatous disease. In 18th Biennial Meeting of the European Society for Immunodeficiencies, Lisbon, Portugal, 24–27 October. Abstract ESID 8-0108.
Uzel G., Orange J.S., Poliak N., Marciano B.E., Heller T., and Holland S.M. 2010. Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis. Clin. Infect. Dis. 51:1429–1434.
van de Geer A., Nieto-Patlán A., Kuhns D.B., Tool A.T., Arias A.A., Bouaziz M., de Boer M., Franco J.L., Gazendam R.P., van Hamme J.L., van Houdt M., van Leeuwen K., Verkuijlen P.J., van den Berg T.K., Alzate J.F., Arango-Franco C.A., Batura V., Bernasconi A.R., Boardman B., Booth C., Burns S.O., Cabarcas F., Bensussan N.C., Charbit-Henrion F., Corveleyn A., Deswarte C., Azcoiti M.E., Foell D., Gallin J.I., Garcés C., Guedes M., Hinze C.H., Holland S.M., Hughes S.M., Ibañez P., Malech H.L., Meyts I., Moncada-Velez M., Moriya K., Neves E., Oleastro M., Perez L., Rattina V., Oleaga-Quintas C., Warner N., Muise A.M., López J.S., Trindade E., Vasconcelos J., Vermeire S., Wittkowski H., Worth A., Abel L., Dinauer M.C., Arkwright P.D., Roos D., Casanova J.L., Kuijpers T.W., and Bustamante J. 2018. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J. Clin. Invest. 128:3957–3975.
van den Berg J.M., van Koppen E., Åhlin A., Belohradsky B.H., Bernatowska E., Corbeel L., Español T., Fischer A., Kurenko-Deptuch M., Mouy R., Petropoulou T., Roesler J., Seger R., Stasia M.J., Valerius N.H., Weening R.S., Wolach B., Roos D., and Kuijpers T.W. 2009. Chronic granulomatous disease: The European experience. PLoS ONE. 4:e5234.
Winkelstein J.A., Marino M.C., Johnston R.B. Jr., Boyle J., Curnutte J., Gallin J.I., Malech H.L., Holland S.M., Ochs H., Quie P., Buckley R.H., Foster C.B., Chanock S.J., and Dickler H. 2000. Chronic granulomatous disease: Report on a national registry of 368 patients. Medicine. 79:155–169.
Wolach B., Gavrieli R., de Boer M., van Leeuwen K., Berger-Achituv S., Stauber T., Ben Ari J., Rottem M., Schlesinger Y., Grisaru-Soen G., Abuzaitoun O., Marcus N., Zion Garty B., Broides A., Levy J., Stepansky P., Etzioni A., Somech R., and Roos D. 2017. Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients. Am. J. Hematol. 92:28–36.
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LymphoSign Journal
Volume 6 • Number 1 • March 2019
Pages: 1 - 16
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Received: 31 August 2018
Accepted: 15 October 2018
Accepted manuscript online: 28 January 2019
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Reinhard A.Seger. 2019. Chronic granulomatous disease 2018: advances in pathophysiology and clinical management. LymphoSign Journal.
6(1): 1-16. https://doi.org/10.14785/lymphosign-2018-0012
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