Person: BARIŞ, SAFA
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
BARIŞ
First Name
SAFA
Name
140 results
Search Results
Now showing 1 - 10 of 140
Publication Metadata only Outcome of hypogammaglobulinemia in children: Immunoglobulin levels as predictors(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2010) ÖZEN, AHMET OĞUZHAN; Ozen, Ahmet; Baris, Safa; Karakoc-Aydiner, Elif; Ozdemir, Cevdet; Bahceciler, Nerin Nadir; Barlan, Isil BeratWe evaluated 131 children (M=88, F=43) with hypogammaglobulinemia Data was analyzed mainly for delineating predictor factors for outcome The distance from the lower limit of normal (-2SD) for any single measurement of immunoglobulins (Ig) was calculated and transformed into Ig scores Mean age and duration of follow up were 5 06 +/- 4 05 and 3 7 +/- 3 03 years, respectively The diagnoses were 22 CVID, 16 IgA deficiency, 33 transient hypogammaglobulinemia of childhood (THC), 3 selective IgM deficiency and 57 unclassified hypogammaglobulinemia (UCH) Low IgA scores (<-0 124) at presentation were indicative of subsequent development of IgA deficiency or CVID, whereas low IgM score (<-0 038) pointed towards more severe and persistent phenotypes Combination of low IgM score between 2 and 5 years, impaired antibody response and low B cell counts enabled us to predict persistence of hypogammaglobulinemia beyond 5 years (specificity = 90 5% and PPV = 94 9%) and chronic lung disease (sensitivity =90 4% and specificity = 68 3%) The set of criteria including low IgM scores, impaired antibody response and low B cell counts provided a high predictive value in detecting those with persistent hypogammaglobulinemia (C) 2010 Elsevier Inc All rights reservedPublication Open Access Outcome of Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome(AMER SOC HEMATOLOGY, 2019-11-13) ÖZEN, AHMET OĞUZHAN; Labrosse, Roxane; Chu, Julia; Armant, Myriam; van der Spek, Jet; Miggelbrink, Alexandra; Fong, Johnson; Everett, John K.; Raymond, Hayley; Kessler, Lyanna; Dansereau, Colleen; Mackinnon, Brenda; Koo, Stephanie; Morris, Emily; London, Wendy B.; Ozen, Ahmet; Baris, Safa; Despotovic, Jenny M.; Forbes, Lisa; Saitoh, Akihiko; Takachi, Takayuki; King, Alejandra; Thi Mai Anh Thi Nguyen; Vy Do Uyen Vu; Bushman, Frederic D.; Galy, Anne; Notarangelo, Luigi; Williams, David A.; Pai, Sung-YunPublication Open Access Immediate adverse reactions to intravenous immunoglobulin in primary immune deficiencies: a single center experience(2020) ÖZEN, AHMET OĞUZHAN; Nain, Ercan; Kıykım, Ayça; Kasap, Nurhan Aruci; Barış, Safa; Özen, Ahmet; Aydıner, Elif KarakoçPublication Open Access Protein Expression in the Diagnosis of LRBA Deficiency by Flow Cytometer(BILIMSEL TIP YAYINEVI, 2017-11-17) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Kiykim, Ayca; Nain, Ercan; Somer, Ayper; Guven, Ayla; Baris, Safa; Ozen, Ahmet; Karakoc Aydiner, ElifObjective: Lipopolysaccharide-responsive beige-like anchor (LRBA) plays a role in cell surface expression of inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4) protein. Recently identified LRBA deficiency leads to immune deficiency and autoimmunity and is diagnosed by mutation analyses and protein expression. Herein, we quantified stimulated and unstimulated intracellular LRBA protein expression by flow cytometry in LRBA deficiency patients. Materials and Methods: Five LRBA deficient patients and seven healthy controls were evaluated. The LRBA expressions were assessed in peripheral-blood-mononuclear-cells in the presence or absence of phorbol-miristat-acetate and ionomycin stimulation. The difference in mean-fluorescence-intensity (Delta MFI) was calculated. Results: The differences in mean-fluorescence-intensity values of LRBA by flow cytometry were 24 +/- 9 for the healthy controls and 4.8 +/- 2.8 for the patients..MFIs were 20.8 for P3, 19 for P4 and 49.6 for healthy controls with stimulants and 4.8, 4.6 and 20.1 respectively without stimulants. Conclusion: As a rapid and widely available assay, flow cytometric assessment of intracellular LRBA expression has been found to be an effective and reliable method in the identification of LRBA deficiency.Publication Metadata only Osteoporosis: An ignored complication of CVID(WILEY, 2011) ÖZEN, AHMET OĞUZHAN; Baris, Safa; Ozen, Ahmet; Ercan, Hulya; Karakoc-Aydiner, Elif; Cagan, Hasret; Ozdemir, Cevdet; Barlan, Metin; Bahceciler, Nerin N.; Barlan, Isil B.Background: Multiple factors in common variable immunodeficiency (CVID) might interfere with optimal growth and maturation and potentially compromise bone health. Methods: We aimed to evaluate bone mineral density (BMD) of patients with CVID using dual energy X-ray absorptiometry (DEXA) and investigate risk factors associated with decreased bone density. Results: Twenty-two patients were included (M: 16, F: 6) with a mean age of 15.6 +/- 9.0 yr. DEXA revealed osteopenia in 6/22 (27.3%) and osteoporosis in 9/22 (40.9%) at lumbar spine and osteopenia in 7/19 (37%) and osteoporosis in 3/19 (16%) at femoral neck sites. The age of subjects with osteoporosis was significantly higher than those without (21.6 +/- 8.0 vs. 9.0 +/- 5.7 yr; p < 0.0001). BMD z-scores were significantly lower in patients with bronchiectasis compared with those without (p = 0.03). Patients with osteoporosis at femoral neck site had lower forced expiratory volume in 1 s (FEV1) (p = 0.024), FEV1/forced vital capacity (FVC) (p < 0.0001), PEF (p = 0.008), and FEF 25-75 (p = 0.013) values compared with the patients with normal BMD z-scores. Low serum 25(OH) vitamin D levels were detected in 13/22 patients and low dietary calcium intake in 17/22 patients. BMD z-scores at femoral neck were lower in patients with low B-cell percentage (p = 0.03). BMD z-score at lumbar spine was correlated with folate (r = +0.63, p = 0.004) and serum immunoglobulin G levels (r = +0.430, p = 0.04). Conclusion: Osteoporosis appeared as an emerging health problem of patients with CVID, the risk increasing with older age and poorer lung function. Nutritional, biochemical, and immunologic factors appeared to take part in decreased BMD. Insight into the mechanisms of osteoporosis in CVID is crucial to develop preventive strategies.Publication Metadata only IPEX olgularında görülen T hücre alt tip yanıtları ve kök hücre nakli ile değişimi(2023-05-01) BARIŞ, SAFA; Barış S.Giriş-Amaç: IPEX sendromu X’e bağlı çekinik olarak aktarılan monogenik bir hastalıktır. Hastalarda FOXP3 (Forkhead box P3) geninde mutasyonlar görülmektedir. FOXP3, Treg hücrelerinin gelişiminde etkili olan bir transkripsiyon faktörüdür. Çalışmamızda IPEX olgularında T hücre alt tiplerinin özellikleri, yeniden programlanma özellikleri ve kök hücre nakli (KIT) sonrası değişimleri incelenerek immün mekanizmaların aydınlatılması amaçlandı. Yöntem: Çalışmamızda farklı merkezlerden dahil edilen İPEX hastalarının (n:12) KİT öncesi ve sonrası klinik ve laboratuvar bulguları değerlendirildi. Nakil öncesi ve sonrası lenfosit alt grupları, proliferasyon, T foliküler hücre (TFH) ve regülatuvar alt tipi (Tfr), Treg ve belirteçleri olan CD25, FOXP3 ve CTLA4 protein ifadeleri analiz edildi. Bulgular: Olguların %83,3 (n=10) otoimmünite, %75 (n=9) kronik ishal, %66,7 (n=8) büyüme-gelişme geriliği, %58,3 (n=7) solunum yolu enfeksiyonları saptandı. Görülen mutasyonlar missense (n=3), del/ins (n=3), kırpılma (n=1) idi. Tüm mutasyonlar türler arasında korunan bölgede saptandı. İlginç olarak hastaların Treg ve Tfr yüzdeleri normal iken, CD25, FOXP3 ve CTLA-4 ifadeleri düşük bulundu. KİT sonrası ifadelerinin normale geldiği saptandı. Ayrıca, hastaların KİT öncesi TFH ve Treg hücrelerinin alt tiplerinde artmış TH2 ve azalmış TH17 yanıtı vardı ve KİT sonrası TH2 yanıtının normalleştiği görüldü. TFH hücrelerinde anormal TH2 yanıtı ile beraber, aktivasyon belirteci olan PD1 ifadesinde artış saptandı. Hastaların lenfosit proliferasyonu ve aktivasyonu normal idi. Sonuç: Çalışmamızda İPEX hastalarında klinik bulgular ve anormal immün yanıtlar ayrıntılı olarak ortaya çıkarılmıştır. Bu hastalarda tanı sırasında Treg hücreleri normal olabilir, ancak Treg belirteçlerinde düşüklük saptanması tanı için şüphe uyandırmalıdır. T hücre alt tip analizlerinde oluşan TH2 yönünde yeniden programlanma klinikte ortaya çıkan bulgular ile örtüşmektedir.(ADT-2022-10661) Anahtar Kelimeler: İPEX, FOXP3, Treg, KİTPublication Open Access ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome(SPRINGER/PLENUM PUBLISHERS, 2018-05) BARIŞ, SAFA; Cagdas, Deniz; Cetinkaya, Pinar Gur; Karaatmaca, Betul; Esenboga, Saliha; Tan, Cagman; Yilmaz, Togay; Gumus, Ersin; Baris, Safa; Kuskonmaz, Baris; Ozgur, Tuba Turul; Bali, Pawan; Santisteban, Ines; Orhan, Diclehan; Yuce, Aysel; Cetinkaya, Duygu; Boztug, Kaan; Hershfield, Michael; Sanal, Ozden; Tezcan, IlhanAdenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T > C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients. The genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.Publication Metadata only CHAPLE disease and non-CHAPLE protein losing enteropathies: natural history and immune characteristics(2021-08-01) SELÇUK, MERVE; BARIŞ, SAFA; ÖZEN, AHMET OĞUZHAN; ÖĞÜLÜR, İSMAİL; AYDINER, ELİF; Selcuk M., Sefer A. P., Baser D., Ogulur I., Eltan S. B., Dursun E., Kocamis B., Kasap N., BARIŞ S., AYDINER E., et al.Publication Open Access Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1(SPRINGER/PLENUM PUBLISHERS, 2016-10) ÖZEN, AHMET OĞUZHAN; Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakir, Mustafa; Boztug, Kaan; Chatila, Talal A.; Barlan, Isil B.Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-gamma/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-gamma and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-beta and -gamma-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.Publication Metadata only Evaluation of a Standardized Bakery Product (SUTMEK) as a Potential Tool for Baked-Milk Tolerance and Immunotherapy Research Studies(KARGER, 2019) ÖZEN, AHMET OĞUZHAN; Kiykim, Ayca; Karakoc-Aydiner, Elif; Gunes, Esra; Nain, Ercan; Ogulur, Ismail; Yazici, Duygu; Aktac, Sule; Bicer, Ayse Humeyra; Sackesen, Cansin; Baris, Safa; Ozen, AhmetBackground and Objectives: About 65-80% of children with IgE-mediated cow's milk allergy (CMA) can tolerate extensively heated milk. We have invested in the mass fabrication of a test product containing milk protein baked at 180 degrees C for 30 min (SUTMEK-milk) and a milk-free placebo (SUTMEK-placebo) to carry out a standardised double-blind placebo-controlled food challenge (DBPCFC) test in patients with CMA. Methods: We studied children with IgE-mediated CMA between 13 and 48 months of age. Specific IgEs (spIgE) to milk proteins were quantified. A DBPCFC with our bakery products was performed, and factors determining reactivity to extensively heated milk were evaluated. We also tested the applicability of SUTMEK products in baked-milk oral immunotherapy in a pilot assessment. Results: We studied 15 children (8 girls, 7 boys) with a median age of 26 months (range: 13-48 months). Nine (60%) patients tolerated a challenge with extensively heated milk, while 6 (40%) were found reactive (anaphylaxis: 2, wheezing: 2, urticaria: 2). spIgE to milk, alpha-lactalbumin, and casein, and the wheal diameter on skin prick testing were higher in the reactive group than the tolerant groups (p = 0.001, p = 0.001, p = 0.002, and p = 0.048, respectively). Receiver-operating characteristic curve analyses yielded the following cut-off values for spIgEs that would predict a reactivity to extensively heated milk; milk: 25 kU/L (area under curve, AUC: 0.981), casein: 32 kU/L (AUC: 0.983), and alpha-lactalbumin: 17 kU/L (AUC: 0.981). Nine patients have tolerated well a continued daily consumption of SUTMEK-milk or -placebo for 6 months at the desired doses. Conclusions: Our bakery products were successfully used in DBPCFC studies and qualified as an acceptable tool for use in the research of interventional tolerance induction. Although spIgE appears useful in determining children at high risk of reacting to extensively heated milk, the predictive cut-off values are still far from being perfect. (c) 2018 S. Karger AG, Basel