Browsing by Author "Kasap, Nurhan"

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Abatacept as a long-term targeted therapy for LRBA deficiency
(Elsevier, 2019-12) Kiykim, Ayça; Ogulur, İsmail; Dursun, Esra; Dogruel, Dilek; Karaca, Neslihan Edeer; Cogurlu, Mujde Tuba; Bilir, Ozlem Arman; Cansever, Murat; Kapakli, Hasan; Baser, Dilek; Kasap, Nurhan; Kutlug, Seyhan; Altintas, Derya Ufuk; Al-Shaibi, Ahmad; Agrebi, Nourhen; Kara, Manolya; Guven, Ayla; Somer, Ayper; Aydogmus, Cigdem; Ayaz, Nuray Aktay; Metin, Ayse; Aydogan, Metin; Uncuoglu, Aysen; Patiroglu, Turkan; Yildiran, Alisan; Guner, Sukru Nail; Keles, Sevgi; Reisli, Ismail; Aksu, Guzide; Kutukculer, Necil; Yilmaz, Mustafa; Karakoc-Aydiner, Elif; Lo, Bernice; Ozan, Ahmet; Chatila, Talal A.; Barıs, Safa; Çekiç, Şükrü; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Dahili Bilimler/Çocuk Sağlığı ve Hastalıkları; Uludağ Üniversitesi/Tıp Fakültesi/Dahili Bilimler/Çocuk Sağlığı ve Hastalıkları; 0000-0002-9574-1842; 0000-0001-8571-2581; L-1933-2017; 57094682600; 7102365439
BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 +/- 7.9 years, and the follow-up period was 3.4 +/- 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.
COVID-19 olan çocuklarda immunoglobulin seviyeleri ve hastane başvuruları üzerine etkisi
(Bursa Uludağ Üniversitesi, 2023-11-28) Kasap, Nurhan; İncealtın, Onur
Koronavirüs hastalığı-2019 (COVID-19) salgını tüm dünyada bir sağlık krizine dönüşmüştür. Çocukların da erişkinler kadar Şiddetli Akut Solunum Sendromu Coronavirüs 2 (SARS-CoV-2) ile enfekte olabildikleri belirlenmiştir. Bu çalışmada, COVID-19 saptanan çocuklarda bakılan immunoglobulin seviyelerini ve hastane başvurularındaki etkisini araştırmayı amaçladık. Ocak 2020 ve Aralık 2022 tarihleri arasında hastaneye başvuran COVID-19 saptanan, immunoglobulin seviyeleri bakılan 138 çocuk hastanın; demografik özellikleri, klinik belirtileri ve laboratuvar sonuçları retrospektif olarak tıbbi kayıtlardan elde edilerek analiz edildi. Olguların %53’ü kız, %47’si erkekti ve yaş ortancaları 9 yıl (0,6–17,8) idi. En sık başvuru semptomları ateş (%52), öksürük (%45) ve gastrointestinal belirtilerdi (%9). IgG %34.5’inde, IgA %14’ünde ve IgM %21.6’sında düşük seviyelerde bulundu. Düşük IgG bulunan hastalarda; IgA, IgM ve IgE seviyelerinde de azalma olduğu saptandı (p<0.001). Düşük IgG olanlarda hemoglobin, total kolesterol ve LDL seviyelerininde de düşüklük görüldü (p=0.015, p=0.036 ve p=0.006, sırasıyla). IgM düşüklüğü olan grupta, normal olan gruba kıyasla hastane yatış gereksinimi daha fazlaydı (p=0.045). Yatış durumu ile cinsiyet, IgG, IgA ve IgE arasında anlamlı ilişki yoktu (p>0,05). Düşük IgA ve IgM seviyeleri olanlarda anlamlı oranda çocuk yoğun bakım ihtiyacı oldugu saptandı (p=0.049, p=0.011, sırasıyla). Uzayan yatış durumu (>15 gün) ile cinsiyet, IgG, IgA, IgM ve IgE arasında istatistiksel olarak anlamlı ilişki yoktu (p>0,05). Hipogammaglobulinemi olan COVID-19 tanılı çocuk hastalarda, genel popülasyona göre mortalite ve yoğun bakım yatış oranlarının daha yüksek olduğu bilinmektedir. Bulgularımız, COVID-19 ile başvuran, hastane yatış gereksinimi olan çocuk hastaların rutin değerlendirmesinde immunoglobulin seviyelerinin değerlendirilmesinin önemini vurgulamaktadır.
Increased radiosensitivity and impaired DNA repair in patients with STAT3-LOF and ZNF341 deficiency, potentially contributing to malignant transformations
(Oxford Univ Press, 2022-05-02) Çekiç, Şükrü; Hüriyet, Hüzeyfe; Hortoğlu, Melika; Kasap, Nurhan; Özen, Ahmet; Karakoç-Aydıner, Elif; Metin, Ayşe; Ocakoğlu, Gökhan; Demiröz Abakay, Candan; Temel, Şehime G.; Özemri Sağ, Şebnem; Barış, Safa; Çavaş, Tolga; Şebnem Kılıç, Sara; ÇEKİÇ, ŞÜKRÜ; Hüriyet, Hüzeyfe; BEKTAŞ HORTOĞLU, MELİKA; OCAKOĞLU, GÖKHAN; DEMİRÖZ ABAKAY, CANDAN; TEMEL, ŞEHİME GÜLSÜN; ÖZEMRİ SAĞ, ŞEBNEM; ÇAVAŞ, TOLGA; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü/Hücre Kültürü ve Genetik Toksikoloji Laboratuvarı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Translasyonel Tıp Anabilim Dalı.; 0000-0002-9574-1842 ; 0000-0002-5617-8313 ; 0000-0001-5380-5898 ; 0000-0003-1620-1918 ; L-1933-2017; CVI-9578-2022; JBJ-7521-2023; HLG-6346-2023; AAH-3855-2021; AAG-8385-2021; AAH-8355-2021; AAH-3508-2021; IMT-6140-2023
STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. The tail length (TL) (mu m), percentage of DNA in the tail (TDNA%), and olive tail moment (OTM) (arbitrary units) were evaluated at the same time for baseline (spontaneous), initial (immediately after 2 Gy irradiation), and recovery (2 h after irradiation) periods by using a computerized image-analysis system, estimating DNA damage. Except for a patient with ZNF341 deficiency who developed nasal cell primitive neuroendocrine tumor and papillary thyroid cancer during the follow-up, there was no cancer in both groups. During the recovery period of irradiation, TL, TDNA%, and OTM values of healthy controls decreased rapidly toward the baseline, while these values of patients with STAT3-LOF and ZNF341 deficiency continued to increase, implying impaired DNA repair mechanisms. Increased radiosensitivity and impaired DNA repair were demonstrated in patients diagnosed with STAT3-LOF and ZNF341 deficiency, potentially explaining the susceptibility to malignant transformation.This study demonstrates for the first time that patients with STAT3-LOF and ZNF341 deficiency had increased radiation sensitivity and DNA repair defects compared with healthy controls. Our results highlight the need for close monitoring of these patients for the development of malignancy.