Imaging of STAT3 deficiency infectious complications
Abstract
Background: Hyper IgE syndrome (HIES) is a primary immunodeficiency with sporadic, autosomal dominant (STAT3 mutation) and autosomal recessive (DOCK8 and TYK2 mutations) inheritance patterns. HIES is characterized by recurrent Staphylococcus infections including lung infections, skin and visceral abcesses, pulmonary pneumatoceles, mucocutaneous candidiasis, and eczematous rash with associated elevated IgE. Patients with STAT3 mutations have additional features including connective tissue, skeletal, dental, and vascular abnormalities.
Methods: This case series highlights the clinical presentation, radiographic findings, and immunologic investigations of 4 siblings with HIES caused by STAT3 mutation.
Results: Our patients presented with infections including Staphylococcus aureus visceral abscesses, skin lesions, pneumonia with associated pneumatocele, and minimal signs of inflammation such as fever. Additional characteristic features included eczematous rash, scoliosis, fractures, and delayed shedding of primary teeth. Immune investigations were essentially unremarkable apart from elevated IgE and eosinophil counts. Detailed imaging identified infectious processes and associated noninfectious features of STAT3 mutations.
Conclusion: Patients presenting with recurrent Staphylococcal cutaneous and visceral infections, pneumatoceles, candidiasis, and eczematous rash with associated elevated IgE should be investigated for STAT3 mutations. This case series highlights the important role of radiographic imaging to identify infectious processes as well as noninfectious associated features in patients with STAT3 mutations.
Statement of novelty: Detailed images of morbidity associated with a STAT3 deficiency.
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REFERENCES
Al-Herz W., Bousfiha A., Casanova J.L., et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency Front. Immunol. 2011 2 54
Avery D.T., Deenick E.K., Ma C.S., et al. B cell intrinsic signaling through IL21 receptor and STAT3 is required for establishing long lived antibody responses in human J. Exp. Med. 2010 207 1 155 -171
Chularojanamontri L., Wimoolchart S., Tuchinda P., Kulthanan K., and Kiewjoy N. Role of omalizumab in a patient with hyper-IgE syndrome and review dermatologic manifestations Asian Pac. J. Allergy. Immunol. 2009 27 4 233 -236
Commins S., Steinke J., and Borish L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, IL-29 J. Allergy. Clin. Immunol. 2008 121 5 1108 -1111
Engelhardt K.R., McGhee S., Winkler S., et al. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal recessive for of hyper-IgE syndrome J. Allergy. Clin. Immunol. 2009 124 6 1289 -1302
Freeman A.F., Avila E.M., Shaw P.A., et al. Coronary artery abnormalities in hyper IgE syndrome J. Clin. Immunol. 2011 31 3 338 -345
Freeman A.F., Collura-Burke C.J., Patronas N.J., et al. Brain abnormalities in patients with hyperimmunoglobulin E syndrome Pediatrics. 2007a 119 5 e1121 -e1125
Freeman A.F., Davis J., Anderson V.L., et al. Pneumocystis jiroveci infection in patients with hyper-immunoglobulin E syndrome Pediatrics. 2006 118 4 e1271 -e1275
Freeman A.F., Kleiner D.E., Nadiminti H., et al. Causes of death in hyper IgE syndrome J. Allergy. Clin. Immunol. 2007b 119 5 1234 -1240
Garty B.Z., Ben-Baruch A., Rolinsky A., Woellner C., Grimbacher B., and Marcus N. Pneumocystis jiroveci pneumonia in a baby with hyper-IgE syndrome Eur. J. Pediatr. 2010 169 1 35 -37
Grimbacher B., Holland S.M., Gallin J.I., et al. Hyper IgE syndrome with recurrent infections - an autosomal dominant multisystem disorder N. Engl. J. Med. 1999a 340 9 692 -702
Grimbacher B., Schäffer A.A., Holland S.M., et al. Genetic linkage of hyper IgE syndrome to chromosome 4 Am. J. Hum. Genet. 1999 65 3 735 -744
Heimall J., Freeman A., and Holland S.M. Pathogenesis of hyper IgE syndrome Clin. Rev. Allergy. Immunol. 2010 38 1 32 -38
Hill H.R. and Quie P.G. Raised serum-IgE levels and defective neutrophil chemotaxis in three children with eczema and recurrent bacterial infections Lancet. 1974 1 183 -187
Hoger P.H., Boltshauser E., and Hitzig W.H. Craniosynostosis in hyper-IgE syndrome Eur. J. of Pediatrics. 1985 144 4 414 -417
Holland S.M., DeLeo F.R., Elloumi H.Z., et al. STAT3 mutations in the hyper-IgE syndrome N. Engl. J. Med. 2007 357 16 1608 -1619
Hutto J.O., Bryan C.S., Greene F.L., White C.J., and Gallin J.I. Cryptococcosis of the colon resembling Crohn's disease in a patient with hyperimmunoglobulinemia E - recuurent infection (Job's) syndrome Gastroenterology. 1988 94 3 808 -812
Jacobs D.H., Macher A.M., Handler R., Bennett J.E., Collen M.J., and Gallin J.I. Esophageal cryptococcosis in a patient with the hyperimmunoglobulin E recurrent infection (Job's) syndrome Gastroenterology. 1984 87 1 201 -203
King C.L., Gallin J.I., Malech H.L., Abramson S.L., and Nutman T.B. Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma Proc. Natl. Acad. Sci. USA. 1989 86 24 10085 -10089
Leonard G.D., Posadas E., Herrmann P.C., et al. Non-Hodgkin's lymphoma in Job's syndrome: a case report and literature review Leuk. Lympoma. 2004 45 12 2521 -2525
Melia E., Freeman A.F., Shea Y.R., Hsu A.P., Holland S.M., and Olivier K.N. Pulmonary nontuberculous mycobacterial infections in hyper-IgE syndrome J. Allergy. Clin. Immunol. 2009 124 3 617 -618
Milner J.D., Brenchley J.M., Laurence A., et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome Nature. 2008 10;452 7188 773 -776
Minegishi Y., Saito M., Morio T., Watanabe K., et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity Immunity. 2006 25 5 745 -755
Minegishi Y., Saito M., Tsuchiya S., et al. Dominant negative mutations in the DNA binding domain of STAT3 cause hyper IgE syndrome Nature. 2007 448 1058 -1062
Olaiwan A., Chandesris M.O., Fraitag S., et al. Cutaneous findings in sporadic and familial autosomal dominant hyper-IgE syndrome: a retrospective, single-center study of 21 patients diagnosed using molecular analysis J. Am. Acad. Dermatol. 2011 65 6 1167 -1172
Ozaki K., Spolski R., Feng C.G., et al. A critical role for IL21 in regulating immunoglobulin production Science. 2002 298 1630 -1634
Renner E.D., Puck J.M., Holland, et al. Autosomal recessive hypergammaglobulin E syndrome: a distinct disease entity J. Pediatr. 2004 144 1 93 -99
Siegel A.M., Heimall J., Freeman A.F., 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 -818
Speckmann C., Enders A., Woellner C., et al. Reduced memory B cells in patients with hyper IgE syndrome Clin. Immunol. 2008 129 3 448 -454
Vihn C.D., Sugui J.A., Hsu A.P., Freeman A.P., and Holland S.M. Invasive fungal disease in autosomal dominant hyper IgE syndrome J. Allergy. Clin. Immunol. 2010 125 6 1389 -1390
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Published In
LymphoSign Journal
Volume 01 • Number 01 • September 2014
Pages: 44 - 54
History
Received: 19 June 2014
Accepted: 27 June 2014
Version of record online: 20 August 2014
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HaynesAlison and MansonDavid. 2014. Imaging of STAT3 deficiency infectious complications. LymphoSign Journal.
01(01): 44-54. https://doi.org/10.14785/lpsn-2014-0005
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