The functionality of immune cells in DOCK8 deficient patients after haematopoietic stem cell transplant — ASN Events
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  2. Poster Session Three
  3. The functionality of immune cells in DOCK8 deficient patients after haematopoietic stem cell transplant

The functionality of immune cells in DOCK8 deficient patients after haematopoietic stem cell transplant (#351)

Bethany A Pillay 1 2 , Danielle T Avery 1 , Jane Peake 3 , Joanne M Smart 4 , Therese Cole 4 , Sharon Choo 4 , Damien Chen 5 , Paul Gray 6 , Melanie Wong 6 , Gulbu Uzel 7 , Alexandra Freeman 7 , Helen C Su 8 , Stuart G Tangye 1 2 , Cindy S Ma 1 2
  1. The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
  3. Lady Cilanto Children’s Hospital, Brisbane, QLD, Australia
  4. Royal Children’s Hosptial, Melbourne, VIC, Australia
  5. Women and Children’s Hospital, Adelaide, SA, Australia
  6. Sydney Children’s Hospital Network, Sydney, NSW, Australia
  7. Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA
  8. Laboratory of Host Diseases, NIAID, NIH, Bethesda, MD, USA

DOCK8 is a guanine nucleotide exchange factor, associated with cell activation and differentiation, which is highly expressed in lymphocytes. Bi-allelic inactivating mutations in DOCK8 cause one of the autosomal recessive forms of hyper IgE syndrome (HIES). DOCK8-deficient patients experience such symptoms as recurrent and severe viral, bacterial and fungal infections, atopic disease including eczema and allergies, especially to food allergens, and impaired humoral responses.
Our previous work has established numerous lymphocyte defects in DOCK8-deficient individuals. This includes decreased proliferation but chronic activation and exhaustion of CD8+ T cells (Randall et al, 2011) and decreased proportions of CD4+ T cells which are impaired in generating Th17 cells but are skewed towards Th2 function (Tangye et al, 2017). Due to the often life threatening nature of the recurrent infections, haematopoietic stem cell transplant (HSCT) has become the standard of care for DOCK8 deficient patients. While reports have detailed the clinical outcomes following HSCT regarding any persisting symptoms, the functionality of immune cells post-transplant within these patients has not been addressed.
To gain a better understanding of cellular function underlying these clinical outcomes we have analysed DOCK8-deficient patients six to twenty three months post-HSCT. Examination of ex vivo as well as in vitro lymphocyte function was undertaken, including investigation of pre-transplant defects to establish if these had been corrected. Chimerism in various cellular subsets was also assessed. Our results provide insight into the efficacy of HSCT to correct cellular defects in DOCK8 patients as well as the correlation between post-transplant clinical outcomes and cellular function in these patients.

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