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Öğe ALLOGENEIC BONE MARROW TRANSPLANTATION IN THREE CASES WITH DOCK 8 DEFICIENCY(Wiley, 2018) Patiroglu, Turkan; Cansever, Murat; Ozcan, Alper; Ucan, Gulsah; Keles, Sevgi; Unal, Ekrem; Talal, Chatila[Abstract Not Availabe]Öğe Atopy and allergic diseases in immunoglobulin A deficiency(Bilimsel Tip Yayinevi, 2012) Artac, Hasibe; Keles, Sevgi; Karagol, Cuneyt; Gokturk, Bahar; Reisli, IsmailObjective: Immunoglobulin (Ig) A deficiency is a common immune system disorder which causes morbidity especially in preschool children. The aim of this study is to evaluate atopy and allergic diseases of cases with IgA deficiency, determinate clinical results before and after four years of age. Materials and Methods: The data records of 295 children with IgA deficiency (272 partial, 23 selective IgA deficiency) between November 2001 and 2007 were examined retrospectively. Results: The mean age at the diagnosis was 64.3 +/- 43 (4-204) months, the mean age at the beginning of infection was 29.5 +/- 36 (1-168) months. There were 121 patients under the age of four years at the diagnosis time. The clinical presentations were recurrent bronchitis (40%), tonsillitis/pharyngitis (33%), sinusitis (6%), pneumonia (4%), acute otitis media (2%), acute gastroenteritis (0.3%) and neck abscess (0.3%), respectively. Eosinophilia was present in 25% of patients, increased IgE levels was present in 38% of patients, and they were correlated with each other. Atopy was detected in 31% of patients by spesific IgE and/or skinprick test positivity. Allergic disease prevalance was found as % 78 (60% asthma, 15% allergic rhinitis, 8% atopic dermatitis, 6% urticaria, 0.7% allergic conjunctivitis). During the clinical follow-up IgA levels reached to normal levels at 17 +/- 14 months ranged between 3 and 60 months. Three patients with selective IgA deficiency had bronchiectasia. Conclusion: We found that allergic diseases were increased in these patients. Serum IgA level should be tested not only for recurrent infections but also for patients with allergic symptoms.Öğe Clinical features and risk factors in children with acute asthma attack(Bilimsel Tip Yayinevi, 2012) Karagol, Cuneyt; Ertoy Karagol, Hacer Ilbilge; Keles, Sevgi; Artafc, Hasibe; Reisli, IsmailObjective: Asthma is one of the most common chronic diseases in childhood and has a high prevalence, morbidity and mortality. Acute asthma attacks are the most significant factor in the determination of the mortality and morbidity of asthma. The aim of this study was to evaluate the risk factors, clinical characteristics and the response of treatment of asthma attacks in children. Patients and Methods: Between January 2008 and January 2009, the clinical characteristics and laboratory findings of 40 children with asthma attack were evaluated. Results: Of 40 children consisting of the study group, 23 were boys and 17 were girls. Mean age was found to be 7.8 +/- 1.9 years. While the most significant risk factors causing attacks were determined as infections and exposure to cigarette smoking, coughing was found as the most frequent symptom during attacks. The severity of the asthma attacks as follows: mild attacks in 20 (50%), moderate attacks in 18 (45%) and severe attacks in 2 (5%) of the patients, respectively. According to the severity of the attacks and response to the treatment, systemic steroid therapy was required in the treatment of 16 (40%) patients while 24 patients improved only with oxigen and short-acting bronchodilator. After the treatment in the emergency unit, 34 (85%) patients were discharged to home and 4 (10%) were hospitalized in the department of pediatrics and 2 (5%) into the intensive care unit. Conclusion: The determination of the risk factors of acute exacerbation is very important to reduce the frequency and the severity of the asthma attacks. We think that the education of the family is necessary to prevent the children with asthma from exposure to smoking and infections.Öğe Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity, Primordial Dwarfism, and Neurological Abnormalities(Wiley-Blackwell, 2013) Jspeert, Hanna I.; Warris, Adilia; van der Flier, Michiel; Reisli, Ismail; Keles, Sevgi; Chishimba, Sandra; van Dongen, Jacques J. M.DNA double-strand break repair via non-homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme radiosensitivity, severe dysmaturity, corpus callosum agenesis, polysyndactily, dysmorphic appearance, and erythema, which are suggestive of a new type of NHEJ deficiency. We identified two heterozygous mutations in LIG4. The p.S205LfsX29 mutation results in lack of the nuclear localization signal and appears to be a null mutation. The second mutation p.K635RfsX10 lacks the C-terminal region responsible for XRCC4 binding and LIG4 stability and activity, and therefore this mutant might be a null mutation as well or have very low residual activity. This is remarkable since Lig4 knockout mice are embryonic lethal and so far in humans no complete LIG4 deficiencies have been described. This case broadens the clinical spectrum of LIG4 deficiencies. Published 2013 Wiley Periodicals, Inc.Öğe Clinical, immunological features and follow up of 20 patients with dedicator of cytokinesis 8 (DOCK8) deficiency(Wiley, 2020) Haskologlu, Sule; Bal, Sevgi Kostel; Islamoglu, Candan; Aytekin, Caner; Guner, Sukru; Sevinc, Selin; Keles, SevgiBiallelic 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.Öğe Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1(Mosby-Elsevier, 2020) Cui, Ye; Keles, Sevgi; Charbonnier, Louis-Marie; Jule, Amelie M.; Henderson, Lauren; Celik, Seyma Celikbilek; Reisli, IsmailBackground: Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored. Objective: We sought to establish the role of DNA polymerase M catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred. Methods: We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase delta (Pol delta) complex, and T- and B-cell antigen receptor repertoire analysis. Results: We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Pol delta complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation disrupts the intramolecular interaction between the POLD1 CysB motif and the catalytic domain and also between POLD1 and the Pol delta subunit POLD2. The patients exhibited decreased numbers of naive CD4 and especially CD8 T cells in favor of effector memory subpopulations. This skewing was associated with oligoclonality and restricted T-cell receptor beta-chain V-J pairing in CD8(+) but not CD4(+) T cells, suggesting that POLDR1060C differentially affects peripheral CD8(+) T-cell expansion and possibly thymic selection. Conclusion: These results identify gene defects in POLD1 as a novel cause of T-cell immunodeficiency.Öğe Combined Immunodeficiency due to DOCK8 Deficiency: A Tribute to Prof. Isil Berat Barlan, M.D.(Turkish Soc Immunology, 2015) Keles, Sevgi; Chatila, TalalThe hyper IgE syndrome (HIES) is an immunodeficiency characterized by recurrent infections, eczema, and elevated serum IgE concentrations. An autosomal dominant form (AD-HIES) is caused by mutations in the transcription factor STAT3 gene. An autosomal recessive form (AR-HIES) was described in 2004, and is particularly over-represented in Turkish population with HIES. Subsequent studies led to the discovery of the gene encoding the Dedicator of Cytokinesis 8 (DOCK8) as the target of mutations in the overwhelming majority of patients with AR-HIES. This review retraces the steps leading to the discovery of DOCK8 deficiency and the critical role played in the process by Prof. Isil Berat Barlan, M.D., as well as detailing our current knowledge of this disorder and future directions in its investigation and therapy.Öğe Dedicator of cytokinesis 8 regulates signal transducer and activator of transcription 3 activation and promotes TH17 cell differentiation(Mosby-Elsevier, 2016) Keles, Sevgi; Charbonnier, Louis Marie; Kabaleeswaran, Venkataraman; Reisli, Ismail; Genel, Ferah; Gulez, Nesrin; Al-Herz, WaleedBackground: The autosomal recessive hyper-IgE syndrome (HIES) caused by dedicator of cytokinesis 8 (DOCK8) deficiency shares clinical features with autosomal dominant HIES because of signal transducer and activator of transcription 3 (STAT3) mutations, including recurrent infections and mucocutaneous candidiasis, which are suggestive of T(H)17 cell dysfunction. The mechanisms underlying this phenotypic overlap are unclear. Objective: We sought to elucidate common mechanisms operating in the different forms of HIES. Methods: We analyzed the differentiation of CD4(+) T-H cell subsets in control and DOCK8-deficient subjects. We also examined the role of DOCK8 in regulating STAT3 activation in T cells. T-H cell differentiation was analyzed by ELISA, flow cytometry, and real-time PCR measurements of cytokines and T-H cell transcription factors. The interaction of DOCK8 and STAT3 signaling pathways was examined by using flow cytometry, immunofluorescence, coimmunoprecipitation, and gene expression analysis. Results: There was a profound block in the differentiation of DOCK8-deficient naive CD4(+) T cells into T(H)17 cells. A missense mutation that disrupts DOCK8 guanine nucleotide exchange factor (GEF) activity while sparing protein expression also impaired T(H)17 cell differentiation. DOCK8 constitutively associated with STAT3 independent of GEF activity, whereas it regulated STAT3 phosphorylation in a GEF activity-dependent manner. DOCK8 also promoted STAT3 translocation to the nucleus and induction of STAT3-dependent gene expression. Conclusion: DOCK8 interacts with STAT3 and regulates its activation and the outcome of STAT3-dependent TH17 differentiation. These findings might explain the phenotypic overlap between DOCK8 deficiency and autosomal dominant HIES.Öğe DO CUT-OFF VALUES OF IgE AND EOSINOPHIL LEVELS HELP DISCRIMINATE HYPERIGE SYNDROME FROM ATOPIC DISEASES?(Springer/Plenum Publishers, 2016) Karakoc-Aydiner, Elif; Kiykim, Ayca; Yuce, Ezgi G.; Baris, Ezgi; Nain, Ercan; Keles, Sevgi; Akturk, Hacer[Abstract Not Availabe]Öğe DOCK8 and STAT3 dependent inhibition of IgE isotype switching by TLR9 ligation in human B cells(Academic Press Inc Elsevier Science, 2017) Massaad, Michel J.; Cangemi, Brittney; Al-Herz, Waleed; LeFranc, Gerard; Freeman, Alexandra; Baxi, Sachin; Keles, Sevgi[Abstract Not Availabe]Öğe DOCK8 Deficiency Presenting as an IPEX-Like Disorder(Springer/Plenum Publishers, 2017) Alroqi, Fayhan J.; Charbonnier, Louis-Marie; Keles, Sevgi; Ghandour, Fatima; Mouawad, Pierre; Sabouneh, Rami; Mohammed, ReemThe dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (T-reg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C > T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G -> A). T-reg cell function was severely compromised by both DOCK8 mutations. DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.Öğe DOCK8 deficiency: Insights into pathophysiology, clinical features and management(Academic Press Inc Elsevier Science, 2017) Biggs, Catherine M.; Keles, Sevgi; Chatila, Talal A.Dedicator of cytokinesis 8 (DOCKS) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoslceleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3. DOCK8 deficiency impairs immune cell migration, function and survival, and it impacts both innate and adaptive immune responses. Clinically, DOCKS deficiency is characterized by allergic inflammation as well as susceptibility towards infections, autoimmunity and malignancy. This review details the pathophysiology, clinical features and management of DOCKS deficiency. It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the emerging spectrum of PIDs resulting from DOCK protein family abnormalities. (C) 2017 Elsevier Inc. All rights reserved.Öğe Efficacy of intravenous immunoglobulin treatment in immunocompromised children with H1N1 influenza: a clinical observation(Wiley-Blackwell, 2016) Gokturk, Bahar; Pekcan, Sevgi; Guner, Sukru Nail; Artac, Hasibe; Keles, Sevgi; Kirac, Mine; Reisli, IsmailBackground and AimsThe appropriate treatment of pandemic H1N1 influenza which was first identified in April 2009 in Mexico is insufficient especially for immunocompromised patients. We aimed to evaluate the features and prognostic factors of the children with H1N1, especially immunocompromised ones, and whether intravenous immunoglobulin G (IVIG) replacement could aid for a better outcome. MethodsTwenty-one hospitalized children with laboratory-confirmed H1N1 were evaluated retrospectively. Data were extracted from files and electronic medical records. ResultsThe median age was 37 (1-216) months; 62% of them were under 5years of age and 71.4% had one or more underlying disorders. Main symptoms were high fever, cough, fatigue and vomiting. Lower respiratory tract manifestations were seen in 66.6% of children. Mortality rate was 4.7%. The patient who died had the lowest lymphocyte (100/mm(3)), thrombocyte (21000/mm(3)) and highest blood urea nitrogen (87mg/dL) levels. Fifty-eight percent of evaluated patients had one of the primary immunodeficiency disorders. Surprisingly, none of the six patients with primary immunodeficiency who are on regular IVIG replacement needed intensive care unit and died. Although median durations of cough, fever and hospitalization were lower, they did not change statistically according to get IVIG replacement regularly (P=0.47, 0.97, 0.09, respectively). ConclusionOur study is important while it is the first one that shows the course of primary immunodeficient children with H1N1 infection who were on regular IVIG replacement. A trial of high-dose IVIG may be a useful adjunctive therapy in severe H1N1 influenza, particularly in the immunocompromised patients.Öğe Evaluation of Clinical and Immunological Characteristics of Children with Common Variable Immunodeficiency(Hindawi Ltd, 2018) Alkan, Gulsum; Keles, Sevgi; Reisli, IsmailBackground. Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder (PID) that typically presents with hypogammaglobulinemia and impaired antibody production. Objectives. This study aimed to promote the awareness of CVID, whose clinical spectrum is quite broad. Methods. The demographic, clinical, and laboratory characteristics of 12 children (seven males and five females) with CVID were analyzed retrospectively. The patients were diagnosed using the diagnostic criteria of the European Society for Primary Immunodeficiencies. Results. The median disease onset age was 7.2 +/- 4.1 years, and the mean diagnosis age was 11.6 +/- 3.7 years. The diagnosis delay was 4.3 +/- 2.6 years, and the parental consanguinity rate was 75%. Most patients presented with recurrent infections, including upper respiratory tract infections (n = 8), lower respiratory tract infections (n = 9), and gastroenteritis (n = 5). In addition, growth retardation (n = 9) and bronchiectasis (n = 5) were common comorbidities. Two patients presented with autoimmune thrombocytopenia and anemia, and one patient exhibited lung empyema. All the patients had immunoglobulin G deficiencies. Conclusion. CVID is a heterogeneous disease, so the diagnosis is frequently delayed. In the CVID patients with pulmonary complications, relationships were seen with the diagnosis delay, symptom onset age, and lung infection prevalence. Overall, the early diagnosis and treatment of PIDs can preclude life-threatening complications.Öğe Evaluation of immunological abnormalities in patients with rare syndromes(Termedia Publishing House Ltd, 2022) Gul, Yahya; Kapakli, Hasan; Aytekin, Selma Erol; Guner, Sukru Nail; Keles, Sevgi; Zamani, Ayse Gul; Yildirim, Mahmut SelmanIntroduction: Recurrent infections are important problems in syndromic patients. This study aimed to evaluate immunological abnormalities in patients who presented with recurrent infections and were diagnosed with rare syndromes. Material and methods: This retrospective analysis included 14 patients with complaints of recurrent infections, all of whom were diagnosed with a rare syndrome. Results: The study group consisted of patients with Aicardi syndrome, Brugada syndrome, Phelan-McDermid syndrome, trichothiodystrophy, LEOPARD syndrome, Prader-Willi syndrome, Seckel syndrome, trisomy 18 (Edwards' syndrome), Wiedemann-Steiner syndrome, West syndrome, Williams syndrome, 47,XYY syndrome, 16p13 deletion syndrome, and 13q1.3 deletion syndrome. Seven patients (50%) were girls and seven (50%) were boys (mean age, 56.7 +/- 32.9 months; median [range] age: 45.5 [27-153] months). There were high rates of consanguinity (50%), cesarean section delivery (71%), and hospitalization in the intensive care unit (78.5%). No patients had a family history of immunodeficiency. On admission, all patients exhibited humoral and/or cellular immune system abnormalities. During the follow-up period, all T-cell abnormalities were improved after immunoglobulin replacement therapy (IGRT), while B-cell abnormalities persisted. These findings suggested that the patients predominantly had antibody deficiencies associated with mild T- cell abnormalities because of recurrent infections. The rates of infections and hospitalizations were significantly reduced after IGRT (p < 0.001); the rate of intensive care unit admission also significantly decreased (from 78.5% to 21.4%). Two of the three oxygen-dependent patients exhibited improvement therein. IGRT was discontinued in two patients with significant clinical improvement during follow-up. Conclusions: An immunological evaluation should be considered in pediatric patients with rare syndromes and recurrent infections. IGRT may help to improve the prognoses of these patients.Öğe Evaluation of the 10 Warning Signs in Primary and Secondary Immunodeficient Patients(Frontiers Media Sa, 2022) Eldeniz, Fadime Ceyda; Gul, Yahya; Yorulmaz, Alaaddin; Guner, Sukru Nail; Keles, Sevgi; Reisli, IsmailObjectivesTen warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID were also sufficient for the diagnosis of SID, and explored the possibility of additional signs. MethodsThis prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each Yes answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. ResultsThe JMF scores of the PID (3.36 +/- 1.65) and SID (3.72 +/- 1.12) groups were significantly higher than the scores of the control group (0.34 +/- 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. ConclusionsThe JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.Öğe The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency(Mosby-Elsevier, 2015) Engelhardt, Karin R.; Gertz, Michael E.; Keles, Sevgi; Schaeffer, Alejandro A.; Sigmund, Elena C.; Glocker, Cristina; Saghafi, ShivaBackground: Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management. Objectives: We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings. Methods: Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations. Results: DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/mu L (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations. Conclusions: DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.Öğe F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in human subjects(Mosby-Elsevier, 2019) Calzoni, Enrica; Platt, Craig D.; Keles, Sevgi; Kuehn, Hye Sun; Beaussant-Cohen, Sarah; Zhang, Yu; Pazmandi, Julia[Abstract Not Availabe]Öğe F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in humans(Springer/Plenum Publishers, 2019) Calzoni, Enrica; Platt, Craig D.; Keles, Sevgi; Kuehn, Hye Sun; Zhang, Yu; Pazmandi, Julia; Lanzi, Gaetana[Abstract Not Availabe]Öğe Hematopoietic stem cell transplantation from unrelated donors in children with DOCK8 deficiency(Wiley, 2017) Uygun, Dilara Fatma K.; Uygun, Vedat; Reisli, Ismail; Keles, Sevgi; Ozen, Ahmet; Yilmaz, Mustafa; Sayar, Esra H.DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile.
