Successful hematopoietic stem cell transplantation after myeloablative conditioning in three patients with dedicator of cytokinesis 8 deficiency (DOCK8) related Hyper …

B Kuşkonmaz, D Ayvaz, İ Tezcan, A Yüce… - Bone Marrow …, 2018 - nature.com
B Kuşkonmaz, D Ayvaz, İ Tezcan, A Yüce, Ö Sanal, DU Çetinkaya
Bone Marrow Transplantation, 2018nature.com
Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal-recessive form of
hyperimmunoglobulin E syndrome which is a primary immunodeficiency (PID), also
classified in the group of combined immunodeficiencies [1]. DOCK8 is a protein within the
family of Rho-GTPases which is expressed in lymphocytes, affects cell signaling and
reorganization of the cytoskeleton [2]. Clinical features of this disease include recurrent
upper and lower respiratory tract infections, elevated IgE levels, eosinophilia, severe atopic …
Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal-recessive form of hyperimmunoglobulin E syndrome which is a primary immunodeficiency (PID), also classified in the group of combined immunodeficiencies [1]. DOCK8 is a protein within the family of Rho-GTPases which is expressed in lymphocytes, affects cell signaling and reorganization of the cytoskeleton [2]. Clinical features of this disease include recurrent upper and lower respiratory tract infections, elevated IgE levels, eosinophilia, severe atopic dermatitis, asthma, and food allergies. Patients with DOCK8 deficiency have increased incidence of viral cutaneous infection; herpes simplex virus, human papilloma virus, and molluscum contagiosum virus. A high risk of malignancy, which is typically hematologic or epithelial, are reported in 8–17% of patients with DOCK8 deficiency [3]. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT) and experience about HSCT in DOCK8 deficiency is limited [4, 5]. Here we report three cases with DOCK8 deficiency who underwent HSCT after myeloablative conditioning in our center. The patients presented characteristic manifestations of DOCK8 deficiency including eczema (all patients), recurrent sinopulmonary infection (all patients), food allergy (Case 1, 3). In case 1 IgE specific for food allergens were as follows; egg white: 33.4 Ku/L (class 4), milk: 37.6 Ku/L (class 4) and nuts: 22.8 Ku/L (class 4). In case 3 food mix test showed 24.4 Ku/L (class 4). Case 3 also had molluscum contagiosum. Additionally, case 2 had resistant giardiasis, sclerosing cholangitis and colitis and case 3 had sclerosing cholangitis. Cryptosporidium was not isolated in the patients with sclerosing cholangitis. Case 3 also had bronchiectasis before HSCT. All three cases were given monthly intravenous immunoglobulin therapy and trimethoprim-sulfomethaxozole prophylaxis. In addition to the clinical features compatible with DOCK8 deficiency, diagnosis was also confirmed with mutational analysis. The details of the mutations are given in the table as given in Table 2.
The donors were human leukocyte antigen (HLA) identical siblings in all patients. Busulfan based myeloablative conditioning regimen was used (Table 1). Cyclosporine A and short-course methotrexate on days+ 1,+ 3,+ 6 were used as graft versus host disease prophylaxis in all patients (Table 1).
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