Disseminated HPV Following Stem Cell Transplant (SCT) in NK(-) Severe Combined Immune Deficiency (SCID) and Association with NK Cell Dysfunction

Abstract

T U E S D A Y 823 Disseminated HPV Following Stem Cell Transplant (SCT) in NK(-) Severe Combined Immune Deficiency (SCID) and Association with NK Cell Dysfunction Kapil Saxena, MS2, Sarah K. Nicholas, MD, Pinaki Banerjee, PhD, Filiz Seeborg, MD, MPH, Theresa Wright, MD, Caridad Martinez, MD, Jordan Orange, MD, PhD, FAAAAI, I. Celine Hanson, MD, FAAAAI; Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, Pediatric Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, TX, Allergy and Immunology Service/ Texas Children’s Hospital/Baylor College of Medicine, Houston, TX, Dermatology Service/Texas Children’s Hospital/Baylor College of Medicine, Houston, TX, Center for Cell and Gene Therapy/Texas Children’s Hospital/Baylor College of Medicine, Houston, TX. RATIONALE: Disseminated Human Papillomavirus (HPV) has been reported post SCT in SCID with NK(-) phenotype and the role of NK cell deficiency minimized. We assessed 4 children with post SCT cutaneous HPV infection in order to assess evidence of donor NK cell engraftment and/or NK cell degranulation/functional activity. METHODS: Retrospective chart review of 65 children with SCID who received SCT between 1986 – 2012. RESULTS: Four of sixty-five children with SCT for SCID from 1986 to 2012 were identified with cutaneous disseminated HPV. All had NK (-) phenotype at SCT. Two received related haploidentical SCT and two matched related donor SCT, none with pre-SCT conditioning. Genetic studies confirmed interluekin-2 receptor mutation in three and no detectable mutation in one. Post SCT, all four had 97-100% T cell donor engraftment and only one patient continued to receive exogenous immunoglobulin supplementation for a protein losing enteropathy of unknown etiology. All four were noted to have persistent poor NK cell representation; CD3(-) 16/56(+) cell percents (patient range of 1-3%) and cell numbers (range of 16-60 cells/mm. Absent NK cell function and/or abnormal degranulation of NK cells was noted in all patients. No patient had detectable serum gamma interferon (gIFN) in the face of disseminated HPV. Topical antiviral therapy failed; three patients have been offered gIFN treatment. CONCLUSIONS: Post SCT disseminated HPVwas only noted in patients with NK (-) phenotype SCID including those without IL2 receptor deficiency. These patients all had persistent profound NK cell deficiency.