Yazar "Erol Çipe, Funda" seçeneğine göre listele
Listeleniyor 1 - 12 / 12
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe Biallelic form of a known CD3E mutation in a patient with severe combined immunodeficiency(Springer/Plenum Publishers, 2020) Erman, Baran; Fırtına, Sinem; Fışgın, Tunç; Bozkurt, Ceyhun; Erol Çipe, FundaT cell receptor (TCR) complex consists of ?? or ?? TCR chains in combination with four CD3 subunits, CD3?, CD3?, CD3?, and CD? [1]. This complex is required for thymocyte development and the initiation of T cell-mediated adaptive immune responses. Although TCR chains bind antigenic peptides presented by MHC molecules, the CD3 subunits provide transduction of signals into the cytosol for the activation and differentiation of T lymphocytes [2]. CD3 deficiencies can cause a rare form of severe combined immunodeficiency (SCID). Although CD3?, CD3?, and CD? mutations usually result in a T- B+ +NK+ SCID phenotype, CD3? deficiency leads to a milder phenotype with autoimmunity [3]. Only 2% of patients with SCID have TCR defects [3]. The T cell antigen receptor epsilon subunit (CD3E) gene is located at 11q23.3 and has been associated with autosomal recessive SCID [4]. Only a few mutations of the CD3E gene have been identified so far [4–8]. Here, we identified the biallelic form of a known CD3E mutation in a patient with a severe T- B+ NK+ phenotypeÖğe Could the COVID-19 infection have a better prognosis than expected in pediatric hematology oncology and bone marrow transplant patients?(AVES, 2021) Öner, Özlem Başoğlu; Aksoy, Başak Adaklı; Yaman, Ayhan; Sütçü, Murat; Erol Çipe, Funda; Atça, Ali Önder; Bozkurt, Ceyhun; Fışgın, TunçCoronavirus disease 2019 (COVID-19) is a pandemic that spread rapidly worldwide (1). So far, very few reports concerning the impact of COVID-19 among patients with pediatric hematologic-oncologic diseases are available (2). We aimed to describe the clinical features, prevalence, treatments, and outcomes in the COVID-19 patient population.Öğe Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency(2020) Ghosh, Sujal; Bal, Sevgi Köstel; Edwards, Emily S J; Pillay, Bethany; Jimenez-Heredia, Raúl; Rao, Geetha; Erol Çipe, Funda; Salzer, Elisabeth; Zoghi, Samaneh; Abolhassani, Hassan; Momen, Tooba; Gostick, Emma; Price, David A; Zhang, Yu; Oler, Andrew J; Gonzaga-Jauregui, Claudia; Erman, Baran; Metin, Ayşe; İlhan, İnci; Haskoloğlu, Şule; İslamoğlu, Candan; Baskın, Kübra; Ceylaner, Serdar; Yılmaz, Ebru; Ünal, Ekrem; Karakukcu, Musa; Berghuis, Dagmar; Cole, Theresa; Gupta, Aditya Kumar; Hauck, Fabian; Hoepelman, Andy; Barış, Safa; Karakoç Aydıner, Elif; Özen, Ahmet; Kager, Leo; Holzinger, Dirk; Paulussen, Michael; Krüger, Renate; Meisel, Roland; Oommen, Prasad Thomas; Morris, Emma C; Neven, Benedicte; Worth, Austen J J; Montfrans, Joris M van; Fraaij, Pieter; Choo, Sharon; Doğu, Figen; Davies, E Graham; Burns, Siobhan; Dueckers, Gregor; Becker, Ruy Perez; Bernuth, Horst von; Latour, Sylvain; Faraci, Maura; Gattorno, Marco; Su, Helen; Pan-Hammarström, Qiang; Hammarström, Lennart; Lenardo, Michael J; Ma, Cindy S; Niehues, Tim; Aghamohammadi, Asghar; Rezaei, Nima; Ikinciogullari, Aydan; Tangye, Stuart G; Lankester, Arjan C; Boztuğ, KaanBiallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity characterized predominantly by EBV-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and malignancy. A comprehensive understanding of the natural history, immune characteristics and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected clinical information of 49 patients from 29 families (CD27 n=33, CD70 n=16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority (90%) of patients were EBV+ at diagnosis, but only ~30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one (43%) patients developed autoinflammatory features including uveitis, arthritis and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.Öğe Genetic screening of the patients with primary immunodeficiency by whole-exome sequencing(New Rochelle, 2020) Erman, Baran; Erol Çipe, FundaBackground: Primary immunodeficiencies (PIDs) are a heterogeneous group of congenital disorders characterized by susceptibility to recurrent infections, allergy, malignancies and autoimmunity. The identification of disease-causing genetic defects is critically important for treatment options. In last decade, next-generation sequencing (NGS)-based methods has enabled the rapid genetic screening and the discovery of new genetic defects in PIDs. In this study, we investigated causative mutations in patients with PID by NGS. Methods: We applied whole-exome sequencing in 8 PID patients. Detected mutations by NGS were validated by Sanger sequencing. Results: We made a genetic diagnosis in 5 of 8 (63%) patients, including 3 novel disease-causing variants. The identified mutations were found in RAG1, RAG2, JAK3, RFXANK, and CYBA genes. Conclusions: Our results show that whole-exome sequencing can facilitate the genetic diagnosis of the patients with PID.Öğe ILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patients(Wiley, 2020) Eken, Ahmet; Cansever, Murat; Okuş, Fatma Zehra; Erdem, Şerife; Nain, Ercan; Azizoğlu, Zehra Büşra; Haliloğlu, Yeşim; Karakukcu, Musa; Özcan, Alper; Devecioğlu, Ömer; Aksu, Güzide; Arıkan Ayyıldız, Zeynep; Topal, Erdem; Karakoç Aydıner, Elif; Kıykım, Ayça; Metin, Ayşe; Erol Çipe, Funda; Kaya, Ayşenur; Artaç, Hasibe; Reisli, İsmail; Güner, Şükrü N.; Uygun, Vedat; Tezcan Karasu, Gülsün; Dönmez Altuntaş, Hamiyet; Canatan, Halit; Oukka, Mohamed; Özen, Ahmet; Chatila, Talal A.; Keleş, Sevgi; Barış, Safa; Ünal, Ekrem; Patıroğlu, TürkanBackgroundDedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. MethodsPeripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays. ResultsDOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls. ConclusionDOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections.Öğe Invasive saprochaete capitata Infection in a patient with autosomal recessive CARD9 deficiency and a review of the literature(Springer/Plenum Publishers, 2020) Erman, Baran; Fırtına, Sinem; Aksoy, Başak Adaklı; Aydoğdu, Selime; Genç, Gonca Erköse; Doğan, Öner; Bozkurt, Ceyhun; Fışgın, Tunç; Erol Çipe, FundaPurpose Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct. Methods The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents. Results S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing. Conclusions This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.Öğe Lymphoma predisposing gene in an extended family: CD70 signaling defect(Springer/Plenum Publishers, 2020) Khodzhaev, Khusan; Bay, Sema Buyukkapu; Kebudi, Rejin; Altındirek, Didem; Kaya, Ayşenur; Erbilgin, Yücel; Ng, Özden Hatırnaz; Kıykım, Ayça; Erol Çipe, Funda; Şen Zengin, Feride; Fırtına, Sinem; Ng, Yuk Yin; Aksoy, Başak Adaklı; Sayitoğlu, MügeGenome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missenseCD70variation was detected (NM_001252.5:c332C>T) in concordance withCD70phenotype and familial segregation was confirmed.CD70variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missenseCD70variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.Öğe Novel frameshift autosomal recessive loss-of-function mutation in SMARCD2 encoding a chromatin remodeling factor mediates granulopoiesis(2021) Yücel, Esra Özek; Karakuş, İbrahim Serhat; Krolo, Ana; Kıykım, Ayça; Heredia, Raul Jimenez; Tamay, Zeynep; Erol Çipe, Funda; Karakoç Aydıner, Elif; Özen, Ahmet; Karaman, Serap; Boztuğ, Kaan; Barış, SafaPurpose: Recently, a new form of congenital neutropenia that is caused by germline biallelic loss-of-function mutations in the SMARCD2 gene was described in four patients. Given the rarity of the condition, the clinical spectrum of the disease has remained elusive. We here report a new patient with a novel frameshift mutation and compare our patient with the previously reported SMARCD2-mutant patients, aiming to provide a more comprehensive understanding of the natural course of the disease. Methods: Clinical and laboratory findings of all reported patients were reviewed. Next-generation sequencing was performed to identify the causative genetic defect. Data on the hematopoietic stem cell transplantation including stem cell sources, conditioning regimen, engraftment, graft-versus-host disease, and infections were also collected. Results: An 11-year-old female patient had a variety of infections including sepsis, deep tissue abscesses, otitis, pneumonia, gingivitis, and diarrhea since infancy. A novel homozygous mutation in SMARCD2 (c.93delG, p.Ala32Argfs*80) was detected. Bone marrow examination showed hypocellularity and decreased neutrophils with diminished granules and myeloid dysplasia, but no blast excess as in previously reported patients. The neutropenia was non-responsive even to higher doses of granulocyte colony-stimulating factor (G-CSF); therefore, the patient was transplanted at 10 years of age from a HLA-A allele–mismatched unrelated donor using a reduced toxicity conditioning regimen and recovered successfully. Compared with the previous four cases, our patient showed longer survival before transplantation without blastic transformation. Conclusion: Distinctive myeloid features and long-term follow-up including therapy options are presented for the newly described case of SMARCD2 deficiency. This disorder is apparent at infancy and requires early transplantation due to the unrelenting disease course despite conventional therapy.Öğe Primary immunodeficiencies: HSCT experiences of a single center in Turkey(WILEY, 2021) Erol Çipe, Funda; Adaklı Aksoy, Başak; Aydoğdu, Selime; Dikme, Gürcan; Kıykım, Ayca; Aydoğmus, Çiğdem; Yücel, Esra; Bozkurt, Ceyhun; Fışgın, TunçBackground Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases. Methods 58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID. Results Of the 58 patients, 38 were male and 20 were female. Median age at transplantation was 12 months (range: 2.5-172 months). Combined immunodeficiencies consisted 67.2% of patients. Mean follow-up time was 27 months (6 months-5 years). Median neutrophil, lymphocyte, and thrombocyte engraftment days were similar in comparison of both donor type and stem cell source. The most common complication was acute GvHD in 15 (25.8%) patients. In total, five patients (31%) belonging to the SCID group and 10 patients (23.8%) belonging to the non-SCID group died. Our total mortality rate was 15 (25.8%) in all patients. Conclusions We would like to present our HSCT experiences as a pediatric immunology transplantation center. Existing severe infections before transplantation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports.Öğe A set of clinical and laboratory markers differentiates hyper-IgE syndrome from severe atopic dermatitis(Elsevier Inc., 2021) Kasap, Nurhan; Çelik, Velat; Işık, Sakine; Cennetoğlu, Pakize; Kıykım, Ayça; Bilgiç Eltan, Sevgi; Nain, Ercan; Oğulur, İsmail; Başer, Dilek; Akkelle, Emre; Çeliksoy, Mehmet Halil; Kocamış, Burcu; Erol Çipe, Funda; Yücelten, Ayşe Deniz; Karakoç Aydıner, Elif; Özen, Ahmet; Barış, SafaHyper-IgE syndrome (HIES) patients may share many features observed in severe atopic dermatitis (SAD), making a diagnostic dilemma for physicians. Determining clinical and laboratory markers that distinguish both disorders could provide early diagnosis and treatment. We analyzed patients (DOCK8 deficiency:14, STAT3-HIES:10, SAD:10) with early-onset SAD. Recurrent upper respiratory tract infection and pneumonia were significantly frequent in HIES than SAD patients. Characteristic facial appearance, retained primary teeth, skin abscess, newborn rash, and pneumatocele were more predictable for STAT3-HIES, while mucocutaneous candidiasis and Herpes infection were common in DOCK8 deficiency, which were unusual in SAD group. DOCK8-deficient patients had lower CD3+ and CD4+T cells with a senescent phenotype that unique for this form of HIES. Both DOCK8 deficiency and STAT3-HIES patients exhibited reduced switched memory B cells compared to the SAD patients. These clinical and laboratory markers are helpful to differentiate HIES from SAD patients.Öğe Single-center study of 72 patients with severe combined immunodeficiency: clinical and laboratory features and outcomes(Springer, 2021) Bayram, Özlem; Haskolo?lu, Şule; Bayrakoğlu, Deniz; Bal, Sevgi Köstel; İslamoğlu, Candan; Erol Çipe, Funda; Kendirli, Tanıl; Kurşun, NazmiyeAbstract: Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life. Purpose and Methods: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997–2017). Results: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T ? B ? NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997–2006) to 85% (2007–2017) during the last 10 years. Conclusions: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study.Öğe Stem cell transplantation for high-risk acute lymphoblastic leukemia in a developing country: a single-center experience(WILEY, 2020) Bozkurt, Ceyhun; Aksoy, B.; Aydoğdu, S.; Bozkurt, Süreyya; Erol Çipe, Funda; Öner, O.; Özsoy, S.; Fışgın, T.: Allogeneic stem cell transplantation in patients with a diagnosis of high-risk acute lymphoblastic leukemia results in high rates of survival in developed countries. Our aim with this presentation was to share our center’s experience on this subject. Methods: Hematopoietic stem cell transplantation was performed in a total of 69 patients with a diagnosis of high-risk acute lymphoblastic leukemia between 2015 and 2020 at our center. The demographic and treatment-related information of the patients was retrospectively evaluated.
