1751. Human Papillomavirus Infection in GATA2 Haploinsufficiency and Treatment with Interferon Alpha
Session: Poster Abstract Session: Viral Infections; Pathogenesis and Epidemiology
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: GATA2 deficiency is a haploinsufficient disease occurring as autosomal dominant or sporadic and is characterized by monocytopenia, B and NK lymphopenia, and NK cell dysfunction, often resulting in opportunistic infections.  Human Papillomavirus (HPV) is the most common infection in GATA2 deficiency, leading to local or disseminated warts in some cases, or invasive carcinoma in others. 

Methods: Retrospective review of all GATA2 patients seen at the NIH 1992-2013. In vitro natural killer (NK) killing of K562 target cells before and after IFNa therapy.

Results: 57 GATA2 deficient patients; 65% had infection with HPV; 53% had severe or recurrent warts, of these 39% had warts involving both upper and lower extremities and 32% had genital warts. HPV infection was typically refractory to cauterization, cryotherapy, and topical therapy. 35% (20 male and female patients) developed HPV-related dysplasia or invasive squamous cell cancers. 4% had head and neck squamous cell cancers.  Reduced NK activity and viral infections suggested problems with interferon alpha (IFNa) activity. In vitro studies on one patient who was subsequently treated with IFNa showed marked improvement in NK cytotoxicity from 8% to 13% and up to 20% with IL-2. This was without any other immune augmentation.  The marked clearing of HPV lesions after bone marrow transplantation suggests immune dysfunction as the underlying correctable defect. Interferonα2b at dose of 1 million units three times weekly was used for refractory warts in 5 patients.  We saw dramatic improvement in the appearance and number of warts.  Interferon alpha was tolerated well without significant toxicities. 

Conclusion: GATA2 haploinsufficiency is associated with high rates of HPV infection, probably reflecting impaired NK activity. Severe cases responded to IFNa therapy. GATA2 deficiency should be considered in those with severe refractory warts, and IFNa may be helpful adjuvant therapy.

Christa Zerbe, MD, MS1, Jennifer Cuellar-Rodriguez, MD1, Lauren Sanchez, MA2, Michael Spinner, BA1, Preet Bagi, MD3, Theo Heller, MD4, Dennis Hickstein, MD5, Amy Hsu, BA1, Emily Mace, PhD6, Pamela Stratton, MD7, Jordan Orange, MD, PhD8 and Steven Holland, MD1, (1)National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD, (2)David Geffen School of Medicine at UCLA, Los Angeles, CA, (3)National Institute of Diabetes and Digestive and Kidney Disorders, The National Institutes of Health, Bethesda, MD, (4)National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, MD, (5)The National Cancer Institute, The National Institutes of Health, Bethesda, MD, (6)Center for Human Immunobiology, Baylor College of Medicine and Texas Chidren's Hospital, Houston, TX, (7)The National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, MD, (8)Director, Center for Human Immunobiology, Baylor College of Medicine/Texas Children's Hospital, Houston, TX

Disclosures:

C. Zerbe, None

J. Cuellar-Rodriguez, None

L. Sanchez, None

M. Spinner, None

P. Bagi, None

T. Heller, None

D. Hickstein, None

A. Hsu, None

E. Mace, None

P. Stratton, None

J. Orange, None

S. Holland, None

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