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Öğe 22q11.2 deletion syndrome: 20 years of experience from two pediatric immunology units and review of clues for diagnosis and disease management(Codon Publications, 2021) Ozen, Selime; Akcal, Omer; Taskirdi, Ilke; Haci, Idil Akay; Karaca, Neslihan Edeer; Gulez, Nesrin; Kutukculer, NecilIntroduction and objectives: The purpose of this study was to evaluate patients diagnosed with 22q11.2 deletion syndrome and determine the clues directing to diagnosis and evaluation of immunological findings for excellent management of the disease. Material and methods: Thirty-three pediatric patients with 22q11.2 deletion syndrome diagnosed between 1998 and 2019 at Pediatric Immunology Division of Ege University Faculty of Medicine and SBU Izmir Dr Behcet Uz Children's Education and Research Hospital were evaluated. Results: This study includes the largest case series reported from Turkey. Congenital cardiac anomalies were the most common pathology associated with the syndrome (90.9%). Hypocalcemic symptoms were observed in 13 patients (40%). Twenty-two of the 33 (66.6%) patients were diagnosed before two years of age. Autoimmune diseases, dysmorphic facial findings, recurrent infections, growth retardation, and speech impairment were other clues for diagnosis in older patients. Clinical spectrum and immunological abnormalities of this syndrome are quite variable. All T-cell subset counts were less than 5th percentile below median by age in one patient (3%) and 10 patients had normal all T-cell subset counts (30.3%). Overall, 69.6% of the patients had normal IgG, IgA, and IgM levels and two patients had panhypogammaglobulinemia. Recurrent infections were revealed in 75.7% of the patients during follow-up. Conclusions: Presence of cardiac anomaly is more helpful in the diagnosis, especially under two years of age. Patients with immunologically high or standard risk did not show any difference in terms of numbers and severity of infections and autoimmunity. (C) 2021 Codon Publications. Published by Codon Publications.Öğe Analysis of IL-1β, TGF-β, IL-5, ACE, PTPN22 gene polymorphisms, and gene expression levels in Turkish children with IgA vasculitis(Springer, 2024) Taskin, Raziye Burcu; Aydin, Ilyas; Aytac, Gulcin; Imamoglu, Suleyman; Tuncay, Secil Conkar; Bulut, Ipek Kaplan; Karaca, Neslihan Edeer; Aksu, Guzide; Berdeli, Afig; Kutukculer, NecilObjective Immunoglobulin-A vasculitis (IgAV) is an inflammatory disease that affects small blood vessels. This study was performed to identify an association between protein tyrosine phosphatase non-receptor type 22 (PTPN22) + 788G > A (rs33996649), transforming growth factor-beta (TGF-beta) -509C > T (rs18004069), interleukin 1-beta (IL-1 beta) -511C > T (rs16944), interleukin 5 (IL-5) -746C/T (rs2069812), and angiotensin-converting enzyme (ACE) I/D (rs4646994) gene polymorphisms, susceptibility to IgAV, as well as the mRNA levels of IL-1 beta, IL-1 beta, and TGF-beta.Method A total of 53 patients with IgAV and 50 healthy controls were enrolled. PTPN22, TGF-beta, IL-1 beta, ACE gene polymorphisms, ACE gene I/D polymorphisms, and mRNA expression levels were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, allele-specific PCR, and real-time PCR with TaqMan kits, respectively.Results PTPN22, TGF-beta, IL-1 beta, IL-5, and ACE variants showed no genotype or allele differences between patients with IgAV and controls. Increased levels of IL-1 beta and TGF-beta mRNA expressions were observed in patients with IgAV (p < 0.001). Patients with the IL-1 beta AG genotype showed significantly increased amounts of arthritis than patients with non-AG (p = 0.004). Age at disease onset was found to be significantly different in patients with IgAV according to the presence of TGF-beta TT genotype (p = 0.047).Conclusion Polymorphisms in PTPN22, TGF-beta, IL-5, IL-1 beta, and ACE genes are unlikely to confer susceptibility to IgAV. However, the presence of the AG genotype of IL-1 beta is associated with susceptibility to IgAV-related arthritis. This is the first study to report a significant increase in serum mRNA levels of IL-1 beta and TGF-beta in IgAV patients, supporting a susceptibility to IgAV in childhood.Öğe 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 Are Proteinase 3 and Cathepsin C Enzymes Related to Pathogenesis of Periodontitis?(Hindawi Publishing Corporation, 2014) Turkoglu, Oya; Azarsiz, Elif; Emingil, Gulnur; Kutukculer, Necil; Atilla, GulAim. Cathepsin C is the activator of the polymorphonuclear leukocyte-derived proteinase 3, which contributes to inflammatory processes. The aim of the present study was to investigate gingival crevicular fluid (GCF) proteinase 3 and cathepsin C levels in periodontal diseases. Design. Eighteen patients with chronic periodontitis (CP), 20 patients with generalized aggressive periodontitis (G-AgP), 20 patients with gingivitis, and 18 healthy subjects were included in the study. Periodontal parameters including probing depth, clinical attachment level, papilla bleeding index, and plaque index were assessed in all study subjects. GCF proteinase 3 and cathepsin C levels were analyzed by ELISA. Results. GCF proteinase 3 total amount was significantly higher in diseased groups compared to control group, after adjusting age(P<0.05). No differences were found in GCF cathepsin C levels among the study groups (P>0.05). Periodontal parameters of sampling sites were positively correlated with GCF proteinase 3 total amounts (P<0.01) but not with cathepsin C total amounts (P>0.05). Conclusions. Elevated levels of GCF proteinase 3 in CP, G-AgP, and gingivitis might suggest that proteinase 3 plays a role during inflammatory periodontal events in host response. However, cathepsin C in GCF does not seem to have an effect on the pathogenesis of periodontal diseases.Öğe Arg753Gln polymorphism of the human toll-like receptor-2 gene in children with recurrent febrile infections(Springer/Plenum Publishers, 2007) Kutukculer, Necil; Yeniay, Betuel Sozeri; Aksu, Guzide; Berdeli, AfigPolymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined. The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and Arg753Gln polymorphism of the TLR-2 gene.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 Associations of interleukin (IL)-1 beta, IL-1 receptor antagonist, and IL-10 with dental caries(Nihon Univ, School Dentistry, 2015) Cogulu, Dilsah; Onay, Huseyin; Ozdemir, Yasemin; Aslan, Gulcin I.; Özkınay, Ferda; Kutukculer, Necil; Eronat, CemalStreptococcus mutans is important in dental caries. Although the role of cytokines in the pathogenesis of dental caries is not clear, components of Streptococcus mutans were found to stimulate production of pro-inflammatory cytokines. We examined the associations of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), and IL-10 with dental caries. Unstimulated whole saliva and blood samples were obtained from 108 children aged 6-12 years with high caries (decayed, missing, or filled teeth [dmft/DMFT] index >4, n = 37), moderate caries (dmft/DMFT = 1-4, n = 37), or caries-free (dmft/DMFT = 0, n = 34). Streptococcus mutans level was classified as low (<10(5) colony-forming units [CFU]/mL) or high (>= 10(5) CFU/mL). Saliva and serum concentrations of IL-1 beta, IL-1ra, and IL-10 were determined by ELISA. IL-1 beta, IL-1ra and IL-10 gene polymorphisms were genotyped using PCR and restriction fragment length polymorphism analysis. The chi-square, Mann-Whitney U, one-way ANOVA, posthoc, Fisher's exact, and t tests were used in statistical analysis. Dental caries was not correlated with salivary or serum concentrations of the studied cytokines. Streptococcus mutans level positively correlated with saliva IL-1 beta concentration and inversely correlated with saliva IL-1ra concentration. There was no correlation of IL-1 beta, IL-1ra, or IL-10 gene polymorphisms with dental caries. Streptococcus mutans is important in stimulating saliva IL-1 beta and inhibiting IL-1ra. Future studies of associations between cytokines and dental caries should investigate additional cytokines and enroll a larger number of participants.Öğe Associations of interleukin (IL)-1 beta, IL-1 receptor antagonist, and IL-10 with dental caries(Nihon Univ, School Dentistry, 2015) Cogulu, Dilsah; Onay, Huseyin; Ozdemir, Yasemin; Aslan, Gulcin I.; Özkınay, Ferda; Kutukculer, Necil; Eronat, CemalStreptococcus mutans is important in dental caries. Although the role of cytokines in the pathogenesis of dental caries is not clear, components of Streptococcus mutans were found to stimulate production of pro-inflammatory cytokines. We examined the associations of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), and IL-10 with dental caries. Unstimulated whole saliva and blood samples were obtained from 108 children aged 6-12 years with high caries (decayed, missing, or filled teeth [dmft/DMFT] index >4, n = 37), moderate caries (dmft/DMFT = 1-4, n = 37), or caries-free (dmft/DMFT = 0, n = 34). Streptococcus mutans level was classified as low (<10(5) colony-forming units [CFU]/mL) or high (>= 10(5) CFU/mL). Saliva and serum concentrations of IL-1 beta, IL-1ra, and IL-10 were determined by ELISA. IL-1 beta, IL-1ra and IL-10 gene polymorphisms were genotyped using PCR and restriction fragment length polymorphism analysis. The chi-square, Mann-Whitney U, one-way ANOVA, posthoc, Fisher's exact, and t tests were used in statistical analysis. Dental caries was not correlated with salivary or serum concentrations of the studied cytokines. Streptococcus mutans level positively correlated with saliva IL-1 beta concentration and inversely correlated with saliva IL-1ra concentration. There was no correlation of IL-1 beta, IL-1ra, or IL-10 gene polymorphisms with dental caries. Streptococcus mutans is important in stimulating saliva IL-1 beta and inhibiting IL-1ra. Future studies of associations between cytokines and dental caries should investigate additional cytokines and enroll a larger number of participants.Öğe Associations of interleukin (IL)-1 beta, IL-1 receptor antagonist, and IL-10 with dental caries(Nihon Univ, School Dentistry, 2015) Cogulu, Dilsah; Onay, Huseyin; Ozdemir, Yasemin; Aslan, Gulcin I.; Özkınay, Ferda; Kutukculer, Necil; Eronat, CemalStreptococcus mutans is important in dental caries. Although the role of cytokines in the pathogenesis of dental caries is not clear, components of Streptococcus mutans were found to stimulate production of pro-inflammatory cytokines. We examined the associations of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), and IL-10 with dental caries. Unstimulated whole saliva and blood samples were obtained from 108 children aged 6-12 years with high caries (decayed, missing, or filled teeth [dmft/DMFT] index >4, n = 37), moderate caries (dmft/DMFT = 1-4, n = 37), or caries-free (dmft/DMFT = 0, n = 34). Streptococcus mutans level was classified as low (<10(5) colony-forming units [CFU]/mL) or high (>= 10(5) CFU/mL). Saliva and serum concentrations of IL-1 beta, IL-1ra, and IL-10 were determined by ELISA. IL-1 beta, IL-1ra and IL-10 gene polymorphisms were genotyped using PCR and restriction fragment length polymorphism analysis. The chi-square, Mann-Whitney U, one-way ANOVA, posthoc, Fisher's exact, and t tests were used in statistical analysis. Dental caries was not correlated with salivary or serum concentrations of the studied cytokines. Streptococcus mutans level positively correlated with saliva IL-1 beta concentration and inversely correlated with saliva IL-1ra concentration. There was no correlation of IL-1 beta, IL-1ra, or IL-10 gene polymorphisms with dental caries. Streptococcus mutans is important in stimulating saliva IL-1 beta and inhibiting IL-1ra. Future studies of associations between cytokines and dental caries should investigate additional cytokines and enroll a larger number of participants.Öğe Autoimmune Cytopenias Are Highly Associated with Inborn Errors of Immunity and They May Be the Initial Presentations in Cases without Severe Infections(Karger, 2024) Taskin, Raziye Burcu; Topyildiz, Ezgi; Karaca, Neslihan Edeer; Aksu, Guzide; Karapinar, Deniz Yilmaz; Kutukculer, NecilIntroduction: Inborn errors of immunity (IEIs) are inherited disorders that present with increased susceptibility to infections as well as noninfectious complications. Due to the aberrant immune functions of patients with IEI, autoimmune cytopenia (AIC) may be the initial finding, which makes diagnosis a challenge. We aimed to evaluate the clinical course, laboratory findings, and treatment response of AIC in children with IEI. Methods: Data of children with autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenic purpura (ITP) were obtained from a retrospective chart review of IEI patients diagnosed and followed in our center. Demographic and clinical features and therapeutic outcomes were evaluated. Immunologic findings were compared between patients with AIHA, ITP, and Evans syndrome (ES). The patients were also divided into two subgroups based on the presence or absence of immune dysregulation diseases (IDDs), and all data were compared between these two groups. Results: Out of 562 patients with IEI, 6% (n: 34) had AIC which were ITP (23.5%), AIHA (35.5%), and ES (41.2%). AIC was the initial finding in 50% of these 34 patients. Patients with ES had a higher mean percentage of CD8+ T lymphocytes than ITP patients (40.77 +/- 20.21% vs. 22.33 +/- 12.48%, p = 0.011). Patients with IDDs were more likely to develop ES (p = 0.004), lymphoproliferation (p = 0.005), and resistance to first-line therapy (p = 0.021) than other IEI groups. Conclusion: This study shows that AIC may be the initial finding of IEI, particularly when lymphoproliferation and resistance to first-line therapy co-occur. Therefore, detailed investigation should be offered to all patients to avoid diagnostic delay.Öğe BCG-osis and tuberculosis in a child with chronic granulomatous disease(Mosby-Elsevier, 2007) Bustamante, Jacinta; Aksu, Guzide; Vogt, Guillaume; De Beaucoudrey, Ludovic; Genel, Ferah; Chapgier, Ariane; Filipe-Santos, Orchide; Feinberg, Jacqueline; Emile, Jean-Francois; Kutukculer, Necil; Casanova, Jean-LaurentA few known primary immunodeficiencies confer predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines (regional disease, known as BCG-itis, or disseminated disease, known as BCG-osis), or more virulent mycobacteria, such as Mycobacterium tuberculosis (pulmonary and disseminated tuberculosis). We investigated the clinical and genetic features of a 12-year-old boy with both recurrent BCG-osis and disseminated tuberculosis. The patient's phagocytic cells produced no 0(2)(-). A hemizygous splice mutation was found in intron 5 of CYBB, leading to a diagnosis of X-linked chronic granulomatous disease. Chronic granulomatous disease should be suspected in all children with BCG-osis, even in the absence of nonmycobacterial infectious diseases, and in selected children with recurrent BCG-itis or severe tuberculosis.Öğe CD4(+)CD25(+)Foxp3(+) T regulatory cells, Th1 (CCR5, IL-2, IFN-gamma) and Th2 (CCR4, IL-4, IL-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency(Sage Publications Inc, 2016) Kutukculer, Necil; Azarsiz, Elif; Aksu, Guzide; Karaca, Neslihan EdeerCommon variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies characterized by decreased serum immunoglobulin G along with a decrease in serum IgA and/or IgM, defective specific antibody production, and recurrent bacterial infections. Abnormal lymphocyte trafficking, dysregulated cellular responses to chemokines, and uncontrolled T cell polarization may be involved in the pathogenesis and may help to understand the clinical complications. We evaluated T helper cell subsets (chemokine receptors CCR4, CCR5, and CCR7), expressions on T lymphocytes, intracellular cytokines - IL-2, IL-4, IL-13, IFN- gamma-on CD4(+) T cells, and expression of CD4(+)CD25(+)Foxp3(+) regulatory T cells of 20 CVID patients and 26 healthy controls. Autoimmune clinical findings and other complications were also determined. Percentages and absolute numbers of CD4(+)CD25(+) Foxp3(+) cells did not show any significant difference between CVID cases and healthy controls nor between severe and moderate disease patients. The only significant difference regarding Th1 and Th2 type intracellular cytokines was the decreased absolute numbers of CD3(+)CD4(+)IL4(+) cells in CVID cases. There were some findings about T helper cell type dominance in CVID patients such as positive correlation between hepatomegaly and high IL-2 and IFN-gamma in CD3(+)CD4(+) cells and very high expression of CCR5 (Th1) on CD3(+)CD4(+) cells in patients with granuloma. Th1 (CCR5) and Th2 (CCR4) type chemokine receptors did not show any dominance in CVID cases. However, frequencies of CCR7 expressing CD3(+) T cells, CD3(+)CD4(+) T helper cells and CD3(+)CD8(+) T cytotoxic cells were significantly lower in severe CVID patients. In addition, presence of autoimmune clinical findings was negatively correlated with CCR7(+) cells. As CCR7 is a key mediator balancing immunity and tolerance in the immune system, the abnormality of this mediator may contribute to the profound immune dysregulation seen in CVID. In addition, Th1 cells seem to be more involved in the disease pathogenesis than Th2 cells.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 Chronic granulamatous disease: Two decades of experience from a paediatric immunology unit in a country with high rate of consangineous marriages(Wiley, 2019) Kutukculer, Necil; Aykut, Ayca; Karaca, Neslihan E.; Durmaz, Asude; Aksu, Guzide; Genel, Ferah; Pariltay, Erhan; Cogulu, Ozgur; Azarsiz, ElifChronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.Öğe CLASS SWITCH RECOMBINATION DEFECTS AND UNIQUE CASES OF CD40 AND CD40L DEFICIENCIES(Springer/Plenum Publishers, 2014) Kutukculer, NecilÖğe A clinical and laboratory approach to the evaluation of innate immunity in pediatric CVID patients(Frontiers Media Sa, 2015) Kutukculer, Necil; Azarsiz, Elif; Karaca, Neslihan Edeer; Ulusoy, Ezgi; Koturoglu, Guldane; Aksu, GuzideDefective adaptive immune responses are well studied in common variable immunodeficiency (CVID) patients; however, more focus is needed on innate immune system defects to explain CVID's clinical and laboratory heterogeneity. This is the first study comparing migratory function of granulocytes, oxidative burst activity of phagocytic cells, surface integrin expressions on neutrophils and lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural killer T cells, lymphocyte subsets such as CD8(+)CD28(+), CD4(+)CTLA-4(+) cells in CVID patients (n: 20) and healthy controls (n: 26). The relationship between laboratory findings and some clinical was also investigated. CD3(+)CD8(+) T cytotoxic cells were found to be elevated in CVID patients, but CD3(+)CD8(+)CD28(+) or CD3(+)CD8(+)CD28(-) cells did not show any significant difference. CD4(+)CTLA-4(+) cell percentages were significantly lower in CVID patients compared to healthy controls. Severe CVID patients had decreased percentages of NK cells with increased NK cell cytotoxicity suggesting possibly increased activation. Furthermore, CD3(-)CD16(+)CD56(+)CD28(+) cells of CVID patients were elevated while percentage of CD28(-) NK cells was decreased. Neutrophil migration percentages were lower but and oxidative burst activity was not affected. CD11a expressions on these cells were depressed in contrast to increased expression of CD18. Innate immunity defects may affect the extent of recurrence and severity of infections in CVID. Our observations highlight some of these associations and indicate the need for further similar studies for improving better innate system evaluation batteries for these patients. Further phenotypic correlations of these analyses will help clinicians reach a more definitive target for the molecular genetic diagnostic of pediatric CVID patients.Öğe A clinical and laboratory approach to the evaluation of innate immunity in pediatric CVID patients(Frontiers Media Sa, 2015) Kutukculer, Necil; Azarsiz, Elif; Karaca, Neslihan Edeer; Ulusoy, Ezgi; Koturoglu, Guldane; Aksu, GuzideDefective adaptive immune responses are well studied in common variable immunodeficiency (CVID) patients; however, more focus is needed on innate immune system defects to explain CVID's clinical and laboratory heterogeneity. This is the first study comparing migratory function of granulocytes, oxidative burst activity of phagocytic cells, surface integrin expressions on neutrophils and lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural killer T cells, lymphocyte subsets such as CD8(+)CD28(+), CD4(+)CTLA-4(+) cells in CVID patients (n: 20) and healthy controls (n: 26). The relationship between laboratory findings and some clinical was also investigated. CD3(+)CD8(+) T cytotoxic cells were found to be elevated in CVID patients, but CD3(+)CD8(+)CD28(+) or CD3(+)CD8(+)CD28(-) cells did not show any significant difference. CD4(+)CTLA-4(+) cell percentages were significantly lower in CVID patients compared to healthy controls. Severe CVID patients had decreased percentages of NK cells with increased NK cell cytotoxicity suggesting possibly increased activation. Furthermore, CD3(-)CD16(+)CD56(+)CD28(+) cells of CVID patients were elevated while percentage of CD28(-) NK cells was decreased. Neutrophil migration percentages were lower but and oxidative burst activity was not affected. CD11a expressions on these cells were depressed in contrast to increased expression of CD18. Innate immunity defects may affect the extent of recurrence and severity of infections in CVID. Our observations highlight some of these associations and indicate the need for further similar studies for improving better innate system evaluation batteries for these patients. Further phenotypic correlations of these analyses will help clinicians reach a more definitive target for the molecular genetic diagnostic of pediatric CVID patients.Öğe A clinical and laboratory approach to the evaluation of innate immunity in pediatric CVID patients(Frontiers Media Sa, 2015) Kutukculer, Necil; Azarsiz, Elif; Karaca, Neslihan Edeer; Ulusoy, Ezgi; Koturoglu, Guldane; Aksu, GuzideDefective adaptive immune responses are well studied in common variable immunodeficiency (CVID) patients; however, more focus is needed on innate immune system defects to explain CVID's clinical and laboratory heterogeneity. This is the first study comparing migratory function of granulocytes, oxidative burst activity of phagocytic cells, surface integrin expressions on neutrophils and lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural killer T cells, lymphocyte subsets such as CD8(+)CD28(+), CD4(+)CTLA-4(+) cells in CVID patients (n: 20) and healthy controls (n: 26). The relationship between laboratory findings and some clinical was also investigated. CD3(+)CD8(+) T cytotoxic cells were found to be elevated in CVID patients, but CD3(+)CD8(+)CD28(+) or CD3(+)CD8(+)CD28(-) cells did not show any significant difference. CD4(+)CTLA-4(+) cell percentages were significantly lower in CVID patients compared to healthy controls. Severe CVID patients had decreased percentages of NK cells with increased NK cell cytotoxicity suggesting possibly increased activation. Furthermore, CD3(-)CD16(+)CD56(+)CD28(+) cells of CVID patients were elevated while percentage of CD28(-) NK cells was decreased. Neutrophil migration percentages were lower but and oxidative burst activity was not affected. CD11a expressions on these cells were depressed in contrast to increased expression of CD18. Innate immunity defects may affect the extent of recurrence and severity of infections in CVID. Our observations highlight some of these associations and indicate the need for further similar studies for improving better innate system evaluation batteries for these patients. Further phenotypic correlations of these analyses will help clinicians reach a more definitive target for the molecular genetic diagnostic of pediatric CVID patients.Öğe Clinical and Laboratory Evaluation of Periodically Monitored Turkish Children with IgG Subclass Deficiencies(Allergy Immunol Soc Thailand,, 2009) Karaca, Neslihan Edeer; Karadeniz, Cem; Aksu, Guzide; Kutukculer, NecilIgG subclass deficiencies are common immune system disorders during childhood. The aim of this retrospective study was to review clinical findings and laboratory results of patients with IgG subclass deficiencies in order to determine the changes in serum IgG subclass levels during follow-up, the percentage and time span until normalization of the IgG subclass levels to age-corresponding normal levels, the type of infections incurred and the benefits of prophylaxis. Among the 59 pediatric patients reviewed, the most frequent defect was an IgG3 subclass deficiency (77%). Nine percent of the patients had an isolated IgG2 deficiency and 14% had an IgG2+G3 deficiency. The most common clinical presentations were recurrent upper respiratory tract infections, followed by pneumonia, acute gastroenteritis and urinary tract infections. Atopy was present in 15% of the patients. Ninety percent of the patients were given a prophylactic treatment (benzathine penicillin, oral antibiotics, oral bacterial lysate or intravenous immunoglobulin). The frequency of recurrent infections decreased from 13.4 +/- 7.4 per year to 5.7 +/- 3.9 in patients receiving a prophylactic regimen. Serum IgG subclass levels reached normal ranges in 30% of the patients in the IgG3 deficiency group and in 35.7% of the patients in the IgG2+G3 deficiency group. Patients with an isolated IgG2 deficiency did not reach age-related normal levels during the study period. Our study shows that IgG subclass levels may normalize in 30 to 40% of patients at about 6 years of age. We emphasize the need of monitoring IgG levels together with the clinical symptomatology in affected individuals and initiate preventive measures when appropriate.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.
