Browsing by Author "Kara, Manolya"

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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.
Primary antibody deficiencies in Turkey: Molecular and clinical aspects
(Humana Press, 2021-09-30) Fırtına, Sinem; Ng, Yuk Yin; Ng, Özden H.; Kıykım, Ayça; Özek, Esra Yücel; Kara, Manolya; Aydıner, Elif; Nepesov, Serdar; Camcıoğlu, Yıldız; Sayar, Esra H.; Güngören, Ezgi Yalçın; Reisli, İsmail; Torun, Selda H.; Haskoloğlu, Şüle; Çoğurlu, Tuba; Kaya, Ayşenur; Çekiç, Şükrü; Barış, Safa; Özbek, Uğur; Özen, Ahmet; Sayitoğlu, Müge; ÇEKİÇ, ŞÜKRÜ; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; 0000-0002-9574-1842; L-1933-2017
Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.
Primary antibody deficiencies in Turkey: Molecular and clinical aspects (oct, 10.1007/s12026-021-09242-z, 2021)
(Springer, 2021-10-19) Fırtına, Sinem; Ng, Yuk Yin; Ng, Ozden H.; Kiykim, Ayca; Ozek, Esra Yucel; Kara, Manolya; Aydiner, Elif; Nepesov, Serdar; Camcioglu, Yildiz; Sayar, Esra H.; Gungoren, Ezgi Yalcin; Reisli, Ismail; Torun, Selda H.; Haskologlu, Sule; Cogurlu, Tuba; Kaya, Aysenur; Baris, Safa; Ozbek, Ugur; Ozen, Ahmet; Sayitoglu, Muge; Çekiç, Şükrü; ÇEKİÇ, ŞÜKRÜ; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-9574-1842; L-1933-2017
The original published version of this article contained a mistake in one of the afliations. The correct afliation of author Manolya Kara (7) should read: Istinye University Faculty of Medicine, VM MedicalPark Pendik Hospital, Pediatric Infectious Diseases Clinic, Istanbul, Turkey The original article has been corrected.