Clinical, immunological features and follow up of 20 patients with dedicator of cytokinesis 8 (DOCK8) deficiency

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Abstract
Biallelic mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a progressive combined immunodeficiency (CID) characterized by susceptibility to severe viral skin infections, atopic diseases, recurrent respiratory infections, and malignancy. Hematopoietic stem cell transplantation (HSCT) is only curative treatment for the disease. However, there is limited information about long‐term outcome of HSCT and its effect to protect against cancer development in DOCK8‐deficient patients. In this study, we retrospectively evaluated clinical and immunologic characteristics of 20 DOCK8‐deficient patients and outcome of 11 patients who underwent HSCT. We aimed to report the experience of our center and the result of the largest transplantation series of DOCK8 deficiency in our country. Median follow‐up time is 71 months (min‐max: 16‐172) in all patients and 48 months (min‐max: 5‐84) in transplanted patients. Atopic dermatitis (18/20), recurrent respiratory tract infections (17/20), and food allergy (14/20) were the most frequent clinical manifestations. Failure to thrive (13/20), liver problems (12/20), bronchiectasis (11/20), chronic diarrhea (10/21), and autism spectrum disorders (3/20) were remarkable findings in our series. Elevated IgE level (20/20) and eosinophilia (17/20), low IgM level (15/20), and decreased CD3+ T (10/20) and CD4+ T (11/20) cell count were prominent laboratory findings. HSCT was performed in 11 patients. All patients achieved adequate engraftment and showed improvement in their clinical and immunologic findings. Atopic dermatitis and food allergies improved in all patients, and their dietary restriction was stopped except one patient who was transplanted recently. The frequency of infections was decreased. The overall survival is 91% in HSCT‐received patients and 80% in all. HSCT at the earliest possible period with most suitable donor‐ and patient‐specific appropriate conditioning regimen and GvHD prophylaxis is lifesaving for DOCK8 deficiency cases.

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