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Öğe Ailesel Akdeniz ateşi tanılı hastalarda hiperkoagulabilite araştırması(Ege Üniversitesi, 2012) Kavaklı, Kaan; Aksu, Güzide; Karaca, Neslihan; Kütükçüler, NecilEnflamasyonun koagülasyon yanıtıyla yakın ilişkisi bir çok çalışmada gösterilmiştir. Enflamasyon hemostatik mekanizmaları tromboz lehine kaydınr. Doğal antikoagülan mekanizmaların sağlıklı fonksiyonu, enflamatuar yanıtın susturulması için gereklidir. Remisyondaki FMF olgulannda zeminde anlamlı olarak artmış enflamasyon önceki çalışmalarda gösterilmiştir. Bu çalışmada daha önceki çalışmamızda, remisyonda ve kolşisin tedavisi alan FMF olgulannda göstermiş olduğumuz hiperkoagulabilite durumununu daha fazla sayıda olguda tedavi öncesi ve tedavisi sonrası dönemde tekrarlanılabilirliliği ve tedavinin koagülasyon parametrelerine etkisinin, ve saptanabilecek koagülasyon anormalliklerinin MEFV mutasyonlarıyla ilişkisinin ayrıntılı araştırması planlanmıştır. Çalışmaya Tel-Hashomer kriterlerine göre FMF tanısı alan 59'u kız, 50'si erkek, 109 olgu alındı. . Bu olgular tedavi öncesi-tanı döneminde ve kolşisin tedavisinin başlamasından 4-6 ay sonra değerlendirildi . Olguların %90'ında kolşisin tedavisine iyi yanıt alındı. TÖ MPV, PLT, ESR, SAA, CRP, INR, PT %, fibrinojen, faktör 8, f PS, AT, APC-R, LA oranı, tPA değerleri TS'a göre anlamlı farklılık gösterdi. MPV, INR, APC-R düzeylerinde tedavi öncesine göre artış; PLT, ESR, SAA, CRP, PT %, fibrinojen, Faktör 8, f PS, AT III, tPA, LA oranı düzeylerinde ise öncesine göre azalma saptandı. Faktör 8 yüzdesi, olgu semptom ve yaş gruplarının çoğunda TÖ ve TS arasında anlamlı farklılık, ve akut toz realctanlanyla pozitif korelasyon gösterdi. Göğüs ağnsılplörit ile ilişkili tek belirleyici ise F 1+2 'nin TÖ bu olgularda daha yüksek saptanmasıydı.. Erizipel varlığıyla ( %16) ilişkili tek belirleyici TÖ PAI-1 değerinin daha düşük olması idi. Olguların % 25'i homozigot, %31'i heterozigot, % 44'ü compound heterozigot MEFV mutasyonuna sahipti. Compound heterozigot olgular homozigot olgularla karşılaştırıldığında, TÖ ve TS 1NR ve LA oranı; TS PT compound heterozigotlarda daha düşük saptandı (p<0.05). Heterozigot ve compound heterozigot olgular karşılaştırıldığında compound heterozigotlarda LA oranı hem TÖ hem TS daha düşük saptandı. Klinik parametreler ve koagülasyon belirteçlerinin tedavi öncesi,sonrası ilişkisi gösterilmiştir.;FMF, hypercoagulabilite, MEFV mutasyonu.;FMF, Hypercoagulabilite, MEFV mutationÖğe Ant-2 Glycoprotein I Antibodies in Children with Rheumatologic Disorders(Springer India, 2019) Azarsiz, Elif; Eman, Gamze; Akarcan, Sanem Eren; Severcan, Ezgi Ulusoy; Karaca, Neslihan; Aksu, Guzide; Kutukculer, NecilAnti-beta-2-glycoprotein I antibodies (anti-2GPI) which are the main antiphospholipid antibodies that characterize the autoimmune antiphospholipid syndrome are pathogenic and are contributing to thrombosis. We aimed to evaluate the presence and the diagnostic importance of these antibodies in children with different rheumatologic diseases with or without thrombosis risk. A total of 100 children with different rheumatologic diseases evaluated retrospectively. The mean anti-2GPI IgG (p=0.108), IgA (p=0.547), and IgM (p=0.807) levels showed no statistically significant difference between different diagnosis groups. But anti-2GPI IgA and IgM levels were higher in SLE patient group. The mean anti-2GPI IgG (p=0.375), IgA (p=0.811), and IgM (p=0.276) levels were not also showed difference between disease groups with/without predisposition to thrombosis even though concentrations were higher in thrombosis group. In children with rheumatological complaints, anti-2GPI antibody measurements should not be the first diagnostic criteria if vasculitis is not thought as the primary defect underlying the clinical symptoms.Öğe Association of clinical and genetical features in FMF with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey(Springer London Ltd, 2012) Ozturk, Can; Halicioglu, Oya; Coker, Isil; Gulez, Nesrin; Sutcuoglu, Sumer; Karaca, Neslihan; Aksu, Guzide; Kutukculer, NecilThe aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF). Records of 452 FMF children living in western Anatolia, Turkey, (12.3 +/- 4.7 years mean) were retrospectively reviewed. Of the 408 patients who met the Tel-Hashomer criteria, 364 were classified into two main groups (two-mutant/one-mutant allele) either of which had three subgroups. The two-mutant allele frequency was 51% and one-mutant allele 38%; 1% had complex-mutant alleles and 10% no mutantalleles. The mean severity score was 8.3 +/- 2.5. Most common clinical features were fever (81.9%), abdominal pain (86.3%) and myalgia (58.8%), and the least common ones: diarrhea (1.7%), protracted febrile myalgia (1.2%) and acute orchitis (1.5%). We detected 33 different genotypes of the MEFV gene: the most common mutant allele was M694V followed by symptomatic allele mutation of E148Q. Although not significantly associated with clinical findings, P369S mutation was not rare (7.5%). Phenotype-genotype correlation revealed that patients with two-allele mutations had more severe clinical presentation and high constipation rate (22.5%); 32.6% of patients with M694V/M694V had splenomegaly. Acute orchitis and protracted febrile myalgia as rare clinical findings were more common in M694V homozygotes. Comparisons of clinical findings among patients with one-mutation allele were made for the first time, but no significant association was found. Positive predictive value of strip assay screening for 12 mutations was recorded as 89%. We suggest that whole sequence analysis for supportive diagnosis of FMF should be performed for selected patients only.Öğe Autoantibody Positivity in Children with Chronic Diarrhea(Galenos Yayincilik, 2020) Tuhan, Hale; Aslan, Asli; Ecevit, Cigdem; Azarsiz, Elif; Karaca, Neslihan; Cetin, Funda; Aksu, GuzideAim: We aimed to determine the frequency of autoantibody antinuclear (ANA), peripheral anti-neutrophil cytoplasmic antibody (p-ANCA), anti-saccharomyces cerevisiae antibody (ASCA), anti-pancreatic exocrine gland antibody (PAb), goblet cell antibody (GAb) positivities in children with the complaint of chronic diarrhea and inflammatory bowel disease (IBD). We also purposed to explore the role of these autoantibodies in the differential diagnosis of IBD. Materials and Methods: in our study, serum samples of 51 patients with the complaint of chronic diarrhea and 35 healthy controls were analyzed. Clinical and laboratory data at the time of serum sampling were collected and a differential diagnosis was made as the results of performed tests were recorded. For all patients, ANA, p-ANCA, ASCA, GAb, PAb positivities were evaluated by indirect immunofluorescence. the chronic diarrhea group was divided into two groups, namely, the IBD group and non-IBD group. Results: in the chronic diarrhea group, 11 (21.6%) patients had ANA, 3 (5.9%) had p-ANCA, 1 (2%) had PAb, 1 (2%) had Gab and 1 (2%) had ASCA positivity. From the 35 cases of the control group, 8 (22.9%) had ANA, 7 (20%) had ASCA positivity. in the control group, ASCA was found to be high (p=0.007). Six cases were diagnosed as IBD; 1 (16.7%) had ANA, 1 (16.7%) had p-ANCA, 1 (2%) had Gab and 1 (2%) had ASCA positivity. ASCA and GAb positivities were significantly more frequent in the IBD group (p=0.006, p=0.006, respectively). Conclusion: ASCA was determined to be significantly higher in the control group. High positivity in the control group showed that the percentage of nonspecific positivity may be high for this test. ASCA and GAb of those patients with a diagnosis of IBD were found significantly higher. the serologic tests which depend on p-ANCA, ASCA, PAb, GAb can be supportive of diagnoses and differential diagnoses of IBD. Autoantibodies in IBD may be used as a supportive diagnostic tool in selected cases, rather than as the diagnosis of IBD as routine practice.Öğe Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?(Sage Publications Inc, 2017) Azarsiz, Elif; Karaca, Neslihan; Levent, Erturk; Kutukculer, Necil; Sozmen, EserBackground Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n=24) and healthy controls (n=23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness - cIMT, brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the mean chitotriosidase activity (8.986.28) was significantly higher than the controls (5.17 +/- 3.42) (P=0.014). Chitotriosidase showed positive relation with hs-CRP (P=0.011) and SAA (P=0.011) but had no relation with ferritin (P=0.155), HDL (P=0.152) or LDL-cholesterol (P=0.380). Mean cIMT increased in patients compared with the controls (P<0.001) but did not show any relation with chitotriosidase (P=0.546). FMD% decreased in patients (P<0.001) also showing no relation with chitotriosidase (P=0.298). Ventricular myocardial performance indexes had no significant difference, but RVEF% decreased in patients (P=0.043). Conclusions High chitotriosidase activity in common variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.Öğe Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor beta 1 Deficiency(Oxford Univ Press Inc, 2014) Ouederni, Monia; Sanal, Ozden; Ikinciogullari, Aydan; Tezcan, Ilhan; Dogu, Figen; Sologuren, Ithaisa; Pedraza-Sanchez, Sigifredo; Keser, Melike; Tanir, Gonul; Nieuwhof, Chris; Colino, Elena; Kumararatne, Dinakantha; Levy, Jacov; Kutukculer, Necil; Aytekin, Caner; Herrera-Ramos, Estefania; Bhatti, Micah; Karaca, Neslihan; Barbouche, Ridha; Broides, Arnon; Goudouris, Ekaterini; Luis Franco, Jose; Parvaneh, Nima; Reisli, Ismail; Strickler, Alexis; Shcherbina, Anna; Somer, Ayper; Segal, Anthony; Angel-Moreno, Alfonso; Luis Lezana-Fernandez, Jose; Bejaoui, Mohamed; Bobadilla-Del Valle, Miriam; Kachboura, Salem; Sentongo, Timothy; Ben-Mustapha, Imen; Bustamante, Jacinta; Picard, Capucine; Puel, Anne; Boisson-Dupuis, Stephanie; Abel, Laurent; Casanova, Jean-Laurent; Rodriguez-Gallego, CarlosBackground. Interleukin 12R beta 1 (IL-12R beta 1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon gamma production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12R beta 1 deficiency. Results. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age +/- standard deviation, 1.5 +/- 7.87 years) than infections with environmental mycobacteria (4.29 +/- 11.9 years), Mycobacterium tuberculosis (4 +/- 3.12 years), or Salmonella species (4.58 +/- 4.17 years) or other rare infections (3 +/- 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guerin. Conclusions. Patients who are deficient in IL-12R beta 1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.Öğe The evaluation of malignancies in Turkish PID patients; A multicenter study(Springer/Plenum Publishers, 2018) Cekic, Sukru; Aytekin, Caner; Metin, Ayse; Karaca, Neslihan; Demirkaya, Metin; Sevinir, Betul; Kutukculer, Necil; Kilic, Sara SebnemÖğe In vitro T lymphocyte proliferation by carboxyfluorescein diacetate succinimidyl ester method is helpful in diagnosing and managing primary immunodeficiencies(Wiley, 2018) Azarsiz, Elif; Karaca, Neslihan; Ergun, Birgul; Durmuscan, Mehmet; Kutukculer, Necil; Aksu, GuzideBackgroundFunctional studies besides routine laboratory tests for the definitive diagnosis of T lymphocyte disorders with isolated T or combined T/B-cell immunodeficiencies are important. We hereby summarized our experience with a carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay for the assessment of mitogenic T-cell proliferation responses in primary immunodeficiency (PID) patients who have not been diagnosed yet or genetically analyzed, but classified as probably having T-cell defects. MethodsUnclassified patients (n=46) and controls (n=25) were evaluated for T-cell disorders with CFSE-based assay. ResultsCD3(+) blast cells after PHA-L stimulation were significantly lower in patients (31.128.8) than controls (67.9 +/- 8.79; P<.001). Nine patients with low and four patients with normal CD3 values had severely decreased blastic transformation. The proliferation response decreased mostly in combined immunodeficiency group. Sixteen of them had impaired proliferation responses. Appropriate molecular genetical analyses were planned after thorough evaluation of each patient. ConclusionsIn vitro lymphocyte cell proliferation analysis by CFSE method is a reliable and practical choice for the assessment of mitogenic T lymphocyte responses in yet unclassified PID patients for targeting further genetical analyses.Öğe Inherited and acquired immunodeficiencies underlying tuberculosis in childhood(Wiley, 2015) Boisson-Dupuis, Stephanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; El Azbaoui, Safaa; Agader, Aomar; Hassani, Amal; El Hafidi, Naima; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, LaurentTuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN- immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.Öğe Mid-Regional Proadrenomedullin Levels in Primary Immunodeficiencies Complicated with Pulmonary Manifestations(Springer India, 2022) Azarsiz, Elif; Karaca, Neslihan; Kutukculer, NecilThe development of lower respiratory complications in children with primary immunodeficiencies characterized by recurrent infections significantly contributes to morbidity and mortality. This is clinically more important and specific in the evaluation of prognosis. The inflammatory response that develops throughout the clinical process can cause the release of several biomarkers. This study aimed to evaluate the inflammatory biomarker mid-regional pro-adrenomedullin (MR-proADM) levels by distribution of lower respiratory tract complications. Plasma MR-proADM levels were measured in children with (n = 52) and without (n = 103) lower respiratory tract complications. The complicated group was also evaluated as infective and non-infective groups. The median MR-proADM levels were higher in the complicated cases (p = 0.175). It was 205.5 (73.4- 562.6) ng/L in the infective group while it was 96.1 (26.1-43.3) ng/L in the non-infective group and the difference between the two groups was statistically significant (p = 0.003). The predictive value of MR-proADM (AUC = 0.749, p = 0.003) was statistically significant compared to CRP (AUC = 0.330, p = 0.040) and SAA (AUC = 0.261, p = 0.004) in the infective group. This study evidences that the MR-proADM levels are higher in PID cases with infective pulmonary complications. Among other markers, MR-proADM appears to be a particularly good predictive inflammation marker for these children.Öğe Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases(Mosby-Elsevier, 2016) Conti, Francesca; Oswaldo Lugo-Reyes, Saul; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Guzide; de Oliveira, Edgar Borges, Jr.; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guerin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G.; Emiroglu, Melike; Oz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Perez, Nestor; Regairaz, Lorena; Guidos Morales, Hector Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Claudia Ortega, Maria; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stephanie; Konte, Barik; Czarna, Ambre; Migaud, Melanie; Pedraza-Sanchez, Sigifredo; Bano Zaidi, Mussaret; Vogt, Guillaume; Blanche, Stephane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stephanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J.; Kutukculer, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, JacintaBackground: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Objective: Our objective was to assess the effect of mycobacterial disease in patients with CGD. Methods: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Results: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Conclusion: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.Öğe Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes(Hindawi Ltd, 2017) Akarcan, Sanem Eren; Karaca, Neslihan; Aksu, Guzide; Bozkaya, Halil; Ayik, Mehmet Fatih; Sahan, Yasemin Ozdemir; Kilinc, Mehmet Arda; Dokumcu, Zafer; Eraslan, Cenk; Divarci, Emre; Alper, Hudaver; Kutukculer, NecilChronic granulomatous disease (CGD) is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91 phox protein (X-linked disease) developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA genemutation affecting p22(phox) protein) had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.Öğe Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants(Springer, 2024) Aykut, Ayca; Durmaz, Asude; Karaca, Neslihan; Gulez, Nesrin; Genel, Ferah; Celmeli, Fatih; Cogurlu, M. TubaHuman Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes. We designed a targeted next-generation sequencing (TNGS) workflow using the Ion AmpliSeq (TM) Primary Immune Deficiency Research Panel to sequence 264 genes associated with IEIs on the Ion S5 (TM) Sequencer. In this study, we report the identification of 38 disease-causing variants, including 16 novel ones, detected in 40 patients across 15 distinct PIRD genes. The application of next-generation sequencing enabled rapid and precise diagnosis of patients with PIRDs.Öğe Severe combined immunodeficiencies: Expanding the mutation spectrum in Turkey and identification of 12 novel variants(Wiley, 2022) Aykut, Ayca; Durmaz, Asude; Karaca, Neslihan; Gulez, Nesrin; Genel, Ferah; Celmeli, Fatih; Ozturk, GulyuzHuman Inborn Errors of Immunity (IEIs) are clinically and genetically heterogeneous group of diseases, with relatively mild clinical course or severe types that can be life-threatening. Severe combined immunodeficiency (SCID) is the most severe form of IEIs, which is caused by monogenic defects that impair the proliferation and function of T, B, and NK cells. According to the most recent report by the International Union of Immunological Societies (IUIS), SCID is caused by mutations in IL2RG, JAK3, FOXN1, CORO1A, PTPRC, CD3D, CD3E, CD247, ADA, AK2, NHEJ1, LIG4, PRKDC, DCLRE1C, RAG1 and RAG2 genes. The targeted next-generation sequencing (TNGS) workflow based on Ion AmpliSeq (TM) Primary Immune Deficiency Research Panel was designed for sequencing 264 IEI-related genes on Ion S5 (TM) Sequencer. Herein, we present 21 disease-causing variants (12 novel) which were identified in 22 patients in eight different SCID genes. Next-generation sequencing allowed a rapid and an accurate diagnosis SCID patients.Öğe Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency(2019) Karaca, Neslihan; Azarsız, Elif; Akarcan, Sanem Eren; Aksu, Güzide; Kütükçüler, NecilThymic maturation evaluation is inevitable for patients with clinical and laboratory findings for a primary immunodeficiency, as the T cellimmunodeficiencies are the most severe type. In this study, we aimed to show the usage of T cell surface molecule “CD31” for the evaluation of thymic output in patients (n: 66) with a large spectrum of findings signing a probable primary immunodeficiency. Besides the classical clinical and laboratory approach for these patients, T cell subpopulations as naive, memory, recent thymic emigrant cells were also investigated. The humoral immunodeficiency (34.8%), combined immunodeficiency (34.8%) and cardiopathy (7.6%) were the most frequent diagnosis groups. CD4+CD45RA+ naive T-cells percentages (p: 0.011) and absolute counts (p: 0.004) and absolute CD4+CD45RA+CD31+ RTE (recent thymic emigrant) cell counts (p: 0.007) were significantly lower in combined immunodeficiency group. Naive T-cells (p: 0.037) and RTE cells (p: 0.032) were also lower in patients who had cardiac surgery in the past. In conclusion, flow cytometric CD31+thymic naive RTE cell evaluation may provide rapid clinical information especially on T-cell immune dysfunction and CD4+CD45RA+CD31+ RTE cells may be used as an alternative to TRECs in the diagnosis of combined immunodeficiencies.Öğe Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency(2019) Karaca, Neslihan; Azarsız, Elif; Akarcan, Sanem Eren; Aksu, Güzide; Kütükçüler, NecilThymic maturation evaluation is inevitable for patients with clinical and laboratory findings for a primary immunodeficiency, as the T cellimmunodeficiencies are the most severe type. in this study, we aimed to show the usage of T cell surface molecule “CD31” for the evaluation of thymic output in patients (n: 66) with a large spectrum of findings signing a probable primary immunodeficiency. Besides the classical clinical and laboratory approach for these patients, T cell subpopulations as naive, memory, recent thymic emigrant cells were also investigated. the humoral immunodeficiency (34.8%), combined immunodeficiency (34.8%) and cardiopathy (7.6%) were the most frequent diagnosis groups. CD4+CD45RA+ naive T-cells percentages (p: 0.011) and absolute counts (p: 0.004) and absolute CD4+CD45RA+CD31+ RTE (recent thymic emigrant) cell counts (p: 0.007) were significantly lower in combined immunodeficiency group. Naive T-cells (p: 0.037) and RTE cells (p: 0.032) were also lower in patients who had cardiac surgery in the past. in conclusion, flow cytometric CD31+thymic naive RTE cell evaluation may provide rapid clinical information especially on T-cell immune dysfunction and CD4+CD45RA+CD31+ RTE cells may be used as an alternative to TRECs in the diagnosis of combined immunodeficiencies.Öğe An unusual manifestation: Papillary thyroid carcinoma in a patient with ataxia-telengiectasia(2016) Aksu, Güzide; Darcan, Şükran; Özen, Samim; Gökşen, Damla; Karaca, Neslihan; Ulusoy, Ezgi; Ertan, YeşimUlusoy E, Edeer-Karaca N, özen S, Ertan Y, Gökşen D, Aksu G, Darcan Ş, Kütükçüler N. An unusual manifestation: Papillary thyroid carcinoma in a patient with ataxia-telengiectasia. Turk J Pediatr 2016; 58: 442-445.Ataxia-telangiectasia (A-T) is a rare autosomal recessive, multisystem, neurodegenerative disorder, characterized by oculocutaneous telangiectasias, variable immunodeficiency and progressive neurological impairment. Definitive diagnosis is made by revealing a disease causing mutation on ATM gene. Missense mutations and polymorphisms of ATM gene can play a role in the development of thyroid papillary carcinoma. A 13-year-old Turkish girl was diagnosed with ataxia telengiectasia at the age of 8 years. When she was 12 years old, multi-nodular goiter was detected by physical examination and ultrasonography. She underwent thyroidectomy and histopathologic investigation revealed a papillary carcinoma with follicular variant. the patient received post-operative radioiodine therapy as well as L-thyroxine treatment because she had residual lesions. Up until now, she is the first Turkish child wit A-T and thyroid carcinoma described in the literature.
