An Unexpected Infection in Loss-of-Function Mutations in STAT3: Malignant Alveolar Echinococcosis in Liver
-
Sule Haskologlu
,
Figen Dogu
,
Gulnur Gollu Bahadır
,
Setenay Akyuzluer
,
Ergin Ciftci
,
Demet Altun
,
Sevgi Keles
,
Meltem Kologlu
,
Aydan Ikinciogullari
Abstract
Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) gene causes autosomal dominant hyper immunoglobulin E syndrome (AD-HIES or Job’s Syndrome), a rare and complex primary immunodeficiency (PID) syndrome characterized by increased levels of IgE (>2000 IU/mL), eosinophilia, recurrent staphylococcal skin abscesses, eczema, recurrent pneumonia, skeletal and connective tissue abnormalities. Although bacterial and fungal infections are common in AD-HIES, susceptibility to parasitic infections has not been reported. Alveolar echinococcosis (AE), a zoonosis caused by the growth of the Echinococcus multilocularis (EM) metacestode, mimics slow-growing liver cancer. The mortality rate of AE is very high when it is diagnosed late or under-treated. Here, we report a 14-year-old boy with AE infections of the liver and the lung resulting in liver failure and diagnosed as STAT3-LOF. To our knowledge, the association between these two conditions has not been reported in the literature before.
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3. Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, "cold", staphylococcal abscesses. Lancet. 1966;1(7445):1013-15.
4. Freeman AF, Holland SM.Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30.
5. Grimbacher B, Holland SM. Gallin JI, Greenberg F, Hill SC, Malech HL, et al.Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999;340(9):692-02.
6. Levy DE, Darnell JE Jr. STATs: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651-62.
7. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, et al. Impaired Th 17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008;452(7188):773-76.
8. De Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17 producing cells. J Exp Med. 2008;205(7):1543-50.
9. Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, et al. Deficiency of Th 17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med. 2008;205(7):1551-57.
10. Speckmann C, Enders A, Woellner C. Reduced memory B cells in patients with hyper IgE syndrome. Clin Immunol 2008;129(3):448-54.
11. Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, et al. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity. 2011;35(5):806-18.
12. Jenna RE, Bergerson MD, Freeman AF. An Update on Syndromes with a Hyper-IgE Phenotype. Immunol Allergy Clin N Am. 2019;39(1):49-61.
13. Eckert J, Deplazes P. Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbial Rev. 2004;17(1):107-35.
14. Altintaş N. Cystic and alveolar echinococcosis in Turkey. Ann Trop Med Parasitol. 1998;92(6):637-642.
15. Craig P. Echinococcus multilocularis. Curr Opin Infect Dis. 2003;16(5):437-44.
16. Vuitton DA, Gottstein B. Echinococcus multilocularis and its intermediate host: a model of parasite-host interplay. J Biomed Biotechnol. 2010;2010:923193.
17. Zhang W, Wen H, Li J, Lin R, McManus DP. Immunology and Immunodiagnosis of Cystic Echinococcosis: An Update. Clin Dev Immunol. 2012.2012:101895.
18. Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, et al. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev. 2019;32(2):e00075-18.
19. Siracusano A, Delunardo F, Teggi A, Ortona E. Cystic Echinococcosis: Aspects of Immune Response, Immunopathogenesis and Immune Evasion from the Human Host. Endocr Metab Immune Disord Drug Targets. 2012;12(1):16-23.
20. Holland SM, DeLeo FR, Elloumi HZ, Hsu AM, Uzel G, Brodsky N. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357(16):1608-19.
21. Godot V, Harraga S, Podoprigora G, Liance M, Bardonnet K, Vuitton DA. IFN alpha-2a protects mice against a helminth infection of the liver and modulates immune responses. Gastroenterology. 2003;124(5):1441-50.
22. Kern P, Wen H, Sato N, Vuitton DA, Gruener B, Shao Y, Delabrousse E, Kratzer W, Bresson-Hadni, S. WHO classification of alveolar echinococcosis: principles and application. Parasitol Int. 2006;55 Suppl:S283-S287.
23. Baron RW, Tanner CE. The effect of immunosuppression on secondaryEchinococcusmultilocularisinfections in mice. Int J Parasitol. 1976;6(1):37-42.
24. Subauste CS. Primary immunodeficiencies and susceptibility to parasitic infections. Parasite Immunol.2006;28(11):567-75.
25. Koch S, Bresson-Hadni S, Miguet JP, Crumbach JP, Gillet M, Mantion GA, et al. Experience of liver transplantation for incurable alveolar echinococcosis: a 45-case Europeancollaborativereport. Transplantation. 2003;75(6):856-63.
26. Chauchet A, Grenouillet F, Knapp J, Richou C, Delabrousse E, Dentan C, et al. Increased incidence and characteristics of alveolar echinococcosis in patients with immunosuppression-associated conditions. Clin Infect Dis. 2014;59(8):1095-04.
27. Lachenmayer A, Gebbers D, Gottstein B, Candinas D, Beldi G. Elevatedincidence of alveolar echinococcosis in immunocompromised patients. Food Waterborne Parasitol. 2019;16:e00060.
2. Holland SM, De Leo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the Hyper-IgE syndrome. N Engl J Med. 2007;18(357):1608-19.
3. Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, "cold", staphylococcal abscesses. Lancet. 1966;1(7445):1013-15.
4. Freeman AF, Holland SM.Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30.
5. Grimbacher B, Holland SM. Gallin JI, Greenberg F, Hill SC, Malech HL, et al.Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999;340(9):692-02.
6. Levy DE, Darnell JE Jr. STATs: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651-62.
7. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, et al. Impaired Th 17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008;452(7188):773-76.
8. De Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17 producing cells. J Exp Med. 2008;205(7):1543-50.
9. Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B, et al. Deficiency of Th 17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med. 2008;205(7):1551-57.
10. Speckmann C, Enders A, Woellner C. Reduced memory B cells in patients with hyper IgE syndrome. Clin Immunol 2008;129(3):448-54.
11. Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, et al. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity. 2011;35(5):806-18.
12. Jenna RE, Bergerson MD, Freeman AF. An Update on Syndromes with a Hyper-IgE Phenotype. Immunol Allergy Clin N Am. 2019;39(1):49-61.
13. Eckert J, Deplazes P. Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbial Rev. 2004;17(1):107-35.
14. Altintaş N. Cystic and alveolar echinococcosis in Turkey. Ann Trop Med Parasitol. 1998;92(6):637-642.
15. Craig P. Echinococcus multilocularis. Curr Opin Infect Dis. 2003;16(5):437-44.
16. Vuitton DA, Gottstein B. Echinococcus multilocularis and its intermediate host: a model of parasite-host interplay. J Biomed Biotechnol. 2010;2010:923193.
17. Zhang W, Wen H, Li J, Lin R, McManus DP. Immunology and Immunodiagnosis of Cystic Echinococcosis: An Update. Clin Dev Immunol. 2012.2012:101895.
18. Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, et al. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev. 2019;32(2):e00075-18.
19. Siracusano A, Delunardo F, Teggi A, Ortona E. Cystic Echinococcosis: Aspects of Immune Response, Immunopathogenesis and Immune Evasion from the Human Host. Endocr Metab Immune Disord Drug Targets. 2012;12(1):16-23.
20. Holland SM, DeLeo FR, Elloumi HZ, Hsu AM, Uzel G, Brodsky N. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357(16):1608-19.
21. Godot V, Harraga S, Podoprigora G, Liance M, Bardonnet K, Vuitton DA. IFN alpha-2a protects mice against a helminth infection of the liver and modulates immune responses. Gastroenterology. 2003;124(5):1441-50.
22. Kern P, Wen H, Sato N, Vuitton DA, Gruener B, Shao Y, Delabrousse E, Kratzer W, Bresson-Hadni, S. WHO classification of alveolar echinococcosis: principles and application. Parasitol Int. 2006;55 Suppl:S283-S287.
23. Baron RW, Tanner CE. The effect of immunosuppression on secondaryEchinococcusmultilocularisinfections in mice. Int J Parasitol. 1976;6(1):37-42.
24. Subauste CS. Primary immunodeficiencies and susceptibility to parasitic infections. Parasite Immunol.2006;28(11):567-75.
25. Koch S, Bresson-Hadni S, Miguet JP, Crumbach JP, Gillet M, Mantion GA, et al. Experience of liver transplantation for incurable alveolar echinococcosis: a 45-case Europeancollaborativereport. Transplantation. 2003;75(6):856-63.
26. Chauchet A, Grenouillet F, Knapp J, Richou C, Delabrousse E, Dentan C, et al. Increased incidence and characteristics of alveolar echinococcosis in patients with immunosuppression-associated conditions. Clin Infect Dis. 2014;59(8):1095-04.
27. Lachenmayer A, Gebbers D, Gottstein B, Candinas D, Beldi G. Elevatedincidence of alveolar echinococcosis in immunocompromised patients. Food Waterborne Parasitol. 2019;16:e00060.
| Files | ||
| Issue | Vol 19 No 6 (2020) | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/ijaai.v19i6.4936 | |
| PMID | 33463136 | |
| Keywords | ||
| Alveolar echinococcosis Autosomal dominant hyper immunoglobulin E syndrome | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Haskologlu S, Dogu F, Gollu Bahadır G, Akyuzluer S, Ciftci E, Altun D, Keles S, Kologlu M, Ikinciogullari A. An Unexpected Infection in Loss-of-Function Mutations in STAT3: Malignant Alveolar Echinococcosis in Liver. Iran J Allergy Asthma Immunol. 2020;19(6):667-675.
