Publications by authors named "Zafer Caliskaner"

17 Publications

  • Page 1 of 1

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common missense variant.

Sci Immunol 2018 12;3(30)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.

Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls ( = 8.37 × 10; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.
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December 2018

B cell aplasia and hypogammaglobulinemia associated with levetiracetam.

Ann Saudi Med 2018 Jan-Feb;38(1):65-68. Epub 2018 Jan 9.

Hulya Ozdemir, Department of Pediatric Immunology and Allergy,, Medical Faculty, Selcuk University,, Alaeddin Keykubat Campus,, 42130 Selcuklu/Konya, Turkey, T: +90 332 2244496, ORCID:

Levetiracetam (LEV) is a second-generation antiepileptic drug approved for the treatment of several types of epilepsy. We report a 45-year-old female who developed hypogammaglobulinemia and B cell aplasia during LEV treatment. The Naranjo probability score for an adverse drug reaction was 6. After LEV discontinuation, the number of B cells gradually increased and reached normal levels within two months. This case suggests that monitoring of immunoglobulin levels and lymphocyte subsets analysis is important in patients treated with LEV, especially in cases of prolonged infections.

Similar Cases Published: 1.
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September 2018

DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

Hum Mol Genet 2015 Dec 16;24(25):7361-72. Epub 2015 Oct 16.

Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg, Freiburg, Germany, Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, UK

Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients.
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December 2015

Safety of subcutaneous immunotherapy with inhalant allergen extracts: a single-center 30-year experience from Turkey.

Immunopharmacol Immunotoxicol 2015 Jun 10;37(3):280-6. Epub 2015 Apr 10.

Division of Immunology and Allergic Diseases, Gulhane Military Medical Academy and Medical School , Ankara , Turkey and.

Context: Although subcutaneous allergen immunotherapy (SCIT) is effective in allergic rhinitis (AR) and asthma, it carries a risk of local and systemic adverse reactions.

Objective: The aim of this study was to evaluate the rates and clinical characteristics of local and systemic reactions (LR and SR), and to identify their relation of demographic features, allergen extracts and diagnosis.

Materials And Methods: This study analyzed the administration of SCIT from 1983 to 2013; involving 1816 patients affected by allergic asthma and/or AR.

Results: The rates of SR from SCIT were 0.078% per injection and 9% per patient. According to the World Allergy Organization 2010 grading system, 91 grade 1 reactions (44%), 67 grade 2 reactions (32.3%), 33 grade 3 reactions (16%) and 16 grade 4 reactions (7.7%) were seen. There was no fatal outcome from any of the SRs. Risk factors for a SR included: aluminium-adsorbed extract, pollen-containing vaccines, large LR and recurrent (≥2) LRs. The total LR rates were 0.062% per injection and 5.2% per patient; the small LR rates were 0.027% per injection and 2.3% per patient, and the large LR rate were 0.035% per injection and 2.9% per patient. Female gender, depot extracts, calcium phosphate-adsorbed extract and pollen vaccines were identified as risk factors for LR.

Conclusion: The analysis of our data over a 30-year period confirmed that SCIT with inhalant allergens conducted strictly according to the standard protocols and when administrated by experienced staff is a safe method of treatment with only a few side-effects.
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June 2015

The knowledge and considerations of the physicians regarding the inhaler devices in asthma and COPD: the INTEDA-1 study.

Tuberk Toraks 2013 ;61(3):183-92

Division of Pediatric Chest Diseases, Faculty of Meram Medicine, Necmettin Erbakan University, Konya, Turkey.

Introduction: The present paper was aimed at indicating and discussing the possible problems related to inhaler devices by considering the knowledge and practices of the physicians regarding the inhalation therapies.

Materials And Methods: The present study is a prospective, cross-sectional survey carried out by Turkish Respiratory Society Inhalation Therapy Group between February 2010 and February 2011 with a participation of ten individual centres. Seven inhaler devices that were available on the market in the country were assessed. The data on the problems that 684 clinicians actively attending patients with respiratory disorders experienced in daily clinical practice or their evaluations of their patients were obtained through the questionnaire.

Results: The respondents, most of whom were pulmonologist (37.5%), and pediatrist (38.1%), had been,on average, 11.6 years in profession. The source of information on inhalers and administration techniques were reported to be mainly the internet and patient leaflets. Of the participants only 18.5% reported to have had adequate knowledge of inhaler devices and proper administration techniques. Most of the participants stated that they themselves provided the instructions of administration and that the method was often verbal explanation. The physicians believed that although approximately 60% of the patients used the drug correctly, 40.7% made critical mistakes to have adverse effects on the therapeutic outcome. The most important criteria on which the physians lay greater emphasis in choosing the inhaler devices were the physical capability, skills and age of the patients.

Conclusion: The awareness of proper use of inhaler devices is a fundamental prerequisite for effective inhalation therapy has been improved in physicians. The results of the present study have shown that more effort is required for professional training. Assisting the physicans with medical personnel for training of the patients and educational motivation are required.
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March 2015

Acute urticaria associated with thyroid papillary carcinoma: a case report.

Ann Dermatol 2012 Nov 8;24(4):453-4. Epub 2012 Nov 8.

Division of Immunology and Allergic Diseases, Gulhane Military Medical Academy and Medical School, Ankara, Turkey.

Although there are several studies showing the association between cancer and urticaria, the mechanisms by which these events occur are not yet known. In this report, a case of acute urticaria with a diagnosis of thyroid papillary carcinoma is presented. Disappearance of treatment-resistant urticarial lesions after thyroidectomy suggests that this association was not a coincidence. The fact that urticaria which was nonresponsive to treatment disappeared spontaneously as a result of tumorectomy, strongly suggests that this association is not a coincidence. To our knowledge, this is the first report of the coexistence of acute urticaria and thyroid papillary carcinoma. This case provides further support that detailed history taking and a thorough physical examination are of paramount importance.
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November 2012

Plasmapheresis in a patient with "refractory" urticarial vasculitis.

Allergy Asthma Immunol Res 2012 Jul 14;4(4):245-7. Epub 2012 Mar 14.

Division of Immunology and Allergic Diseases, Gülhane Military Medical Academy and Medical School, Ankara, Turkey.

Immune complexes are found in the circulation of 30%-75% of patients with urticarial vasculitis and much evidence supports the role of these immune complexes in the pathogenesis of urticarial vasculitis. Plasmapheresis is effective for removing these immune complexes; however, there are few reports on the use of plasmapheresis in the treatment of urticarial vasculitis. We describe a case of "refractory" urticarial vasculitis in which the symptoms improved after plasmapheresis treatment. We suggest that plasmapheresis be considered as an option in patients with severe or treatment-resistant urticarial vasculitis.
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July 2012

Chronic urticaria in patients with autoimmune thyroiditis: significance of severity of thyroid gland inflammation.

Indian J Dermatol Venereol Leprol 2011 Jul-Aug;77(4):477-82

Department of Internal Medicine, Division of Allergy, Ankara, Turkey.

Background: There is a clear association between autoimmune thyroiditis (AT) and chronic urticaria/angioedema (CUA). However, not all patients with AT demonstrate urticaria.

Aims: The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP) was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not.

Methods: Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1) and 28 patients without urticaria (Group 2) were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained.

Results: All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively) (P=0.358). Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012). Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282). In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015) was associated with the remission of urticaria.

Conclusion: In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.
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May 2012

Risk factors for oral allergy syndrome in patients with seasonal allergic rhinitis.

Med Oral Patol Oral Cir Bucal 2011 May 1;16(3):e312-6. Epub 2011 May 1.

Gulhane Military Medical Academy and School of Medicine, Gulhane Training Hospital, Department of Internal Medicine, Ankara, Turkey.

Background: Oral allergy syndrome (OAS) is a unique allergic reaction to food, which is caused by cross-reactivity between proteins in fresh fruits or vegetables and pollens. Predisposing factors for OAS are not well known in patients with seasonal allergic rhinitis.

Objective: Identify the probable risk factors for OAS in patients with seasonal allergic rhinitis.

Study Design: One hundred and eleven consecutive patients with seasonal allergic rhinitis were included. Patients were evaluated in terms of symptom scores and skin prick test positivity scores. Prick-by-prick tests with the fresh fruit or vegetable were carried out in patients who describe oral allergy syndrome. Patients with OAS and without OAS were compared statistically.

Results: OAS was more frequent in females than males (p=0.01). Odds ratio for gender (male/female) was 3.80 (95% confidence interval: 1.28-11.32). Within nasal symptoms, only nasal itching was related with OAS (P<0.05). The logistic regression analysis revealed a significant association between the prevalence of the OAS and age, asthma, TSS and TSTP (p<0.05).

Conclusion: Not all patients with seasonal allergic rhinitis develop OAS. It is likely that, patients with OAS have some additional risk factors other than atopy.
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May 2011

Atopy is a risk factor for acute appendicitis? A prospective clinical study.

J Gastrointest Surg 2008 Jul 19;12(7):1251-6. Epub 2008 Mar 19.

Department of General Surgery, Gulhane Military Medical Academy (GATA), 06018 Etlik, Ankara, Turkey.

Purpose: The purpose of the study was to assess the role of atopy on the development of appendicitis. Acute appendicitis is the most common indication for emergent laparotomy especially in the late teens and early 20s. The pathogenesis generally begins with luminal obstruction caused by fecal mass, seeds, stricture, and bacterial, parasitic, or viral infections. The present study was designed to evaluate whether allergic reaction is indeed an undefined leading factor for luminal obstruction.

Material And Methods: Mix inhalant and food prick tests were performed in 111 patients who underwent appendectomy for acute appendicitis and in 100 control patients. The material of appendectomy was examined, acute appendicitis was verified and graded according to the severity of inflammation and eosinophilic infiltration rate in the wall of appendix by a pathologist. Demographic data were recorded, and peripheral eosinophil count was also performed.

Results: Mix prick test of 33 patients (29.7%) and food prick test of 14 patients (12.6%) were positive in study group when compared with 7 patients (7%) and 1 patient (1%) in control group (p < 0.001). A total of 38 patients (34.2%) in the study group were reactive with mix or food prick test when compared with 8 patients (8%) in control group. There was no significant difference between eosinophilic infiltration rate, peripheral eosinophil count, severity of inflammation, and Alvarado score of mix prick test positive and negative patients in study group.

Conclusion: Atopy incidence in patients with acute appendicitis was significantly higher when compared with control group. However, eosinophilic infiltration rate, inflammation grade, and peripheral eosinophil count were not able to explain the relationship between the two conditions. Atopy is a risk factor for acute appendicitis.
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July 2008

Hypersensitivity to aeroallergens in patients with recurrent vulvovaginitis of undetermined etiology.

J Obstet Gynaecol Res 2007 Aug;33(4):496-500

Gulhane Military Medical Academy and Medical Faculty, Department of Allergy, Ankara, Turkey.

Aim: Recent findings show that the vaginal mucosa can develop an allergic response to environmental allergens and there is a strong association between atopy and some recurrent vulvovaginal infections. In this study, we investigated prospectively the rate of atopy in patients with recurrent vulvovaginitis of undetermined etiology (RVV).

Material And Methods: After being investigated by a gynecologist, 35 patients with RVV who were considered as undetermined etiology formed the study group. The control group consisted of 150 healthy females. Study and control groups were investigated for atopy by means of skin prick test for common aeroallergens. Associated allergic disease and familial atopy history of the subjects were recorded.

Results: The rate of atopy (11/35; 31.4% vs 9/150; 6%) was significantly higher (P < 0.001) in the study group than in the controls. Familial history of atopy was significantly more frequent in the study group than in the controls (10/35; 28.6% vs 8/150; 5.3%, P < 0.05). RVV in atopics is more associated with seasonal rhinitis than in nonatopics (5/11; 45.4% vs 2/24; 8.3%, P < 0.05).

Conclusion: We concluded that a significant number of RVV is associated with atopy. Although the exact mechanism(s) of this relationship remains to be investigated atopy might be a causative and/or contributing factor in the pathogenesis of RVV.
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August 2007

Intranasal fungi and chronic rhinosinusitis: what is the relationship?

Ann Otol Rhinol Laryngol 2007 Jun;116(6):425-9

Department of Otorhinolaryngology-Head and Neck Surgery, Gülhane Medical School, Ankara, Turkey.

Objectives: The aim of this study was to investigate the effects of intranasal fungi on chronic rhinosinusitis (CRS).

Methods: Forty-one patients with CRS were included in the study. The patients were put into 2 groups, with and without intranasal fungi as detected by polymerase chain reaction, and were compared in terms of different laboratory and clinical parameters of CRS. A chi2 test was used to analyze statistical differences between the 2 groups.

Results: Serum eosinophilia, eosinophilia in the nasal mucus, prick and intradermal test positivity for fungi, elevated total IgE, fungal-specific IgE, prevalence of symptoms, frequency of bronchial asthma, aspirin sensitivity, and nasal polyposis did not differ significantly between the 2 groups of patients (p > .05).

Conclusions: The findings of this study failed to reveal a clear correlation between the presence of fungi in the nasal passage and various factors that are assumed to be involved in the pathogenesis or clinical course of CRS. If fungi have a role in the pathogenesis of CRS, it may be via other mediators and reactions rather than IgE and type I hypersensitivity. However, the sample size was relatively small, and further studies with more cases are needed on the same topic.
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June 2007

Heart rate variability in patients with allergic rhinitis.

Mil Med 2007 Jan;172(1):98-101

Cardiology Department, Gulhane Military Medical Academy School of Medicine, Ankara, Turkey.

Considering the role of autonomic imbalance in the pathogenesis of hypersensitivity reactions, we evaluated the autonomic system through time-domain analysis of heart rate variability (HRV) in patients with allergic rhinitis. Twenty-four patients with allergic rhinitis and 22 healthy subjects (mean age, 41 +/- 8 years and 37 +/- 9 years, respectively) were enrolled in the study. The diagnosis of allergic rhinitis was based on the history, symptoms, and skin prick tests results. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time-domain indices were analyzed. Analysis of HRV revealed that the SD of normal RR intervals, SD of successive differences in normal cycles, and HRV triangular index were not significantly different between the groups, but the root mean square successive difference, number of RR intervals exceeding 50 milliseconds, and percentage difference between adjacent normal RR intervals exceeding >50 milliseconds were significantly greater in the study group, compared with the control group. Our findings showed that HRV indices, which predict parasympathetic predominance, were increased in patients with allergic rhinitis. This finding shows that vagal activation is present not only in the nose but also in other systems, including the cardiovascular system.
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January 2007

Radiofrequency for the treatment of vasomotor rhinitis.

Kulak Burun Bogaz Ihtis Derg 2005 ;14(5-6):110-5

Department of Otolaryngology, Gülhane Military Medical School, Ankara, Turkey.

Objectives: We assessed the efficacy of submucosal application of radiofrequency to the inferior turbinate for the treatment of vasomotor rhinitis.

Patients And Methods: Twenty patients with vasomotor rhinitis (9 males, 11 females; mean age 29.2 years; range 20 to 40 years) were treated with radiofrequency applied to the inferior turbinate. Symptoms such as nasal obstruction, sneezing, and watery nasal discharge were graded with the use of a visual analog scale (VAS) before, and on days 1, 3, 7, 30, 60, 90, and 180 after the treatment.

Results: The severity of symptoms began to decrease following the first week after the application. Maximum relief was achieved between 30 to 60 days after the intervention. The highest rate of improvement (85.4%) was reported in sneezing, followed by nasal obstruction (76.4%) and nasal discharge (67.7%). The mean VAS scores showed a significant improvement in all symptoms between 7 to 180 days after the procedure (p<0.05). The rate of patient satisfaction was 90% for the relief of nasal obstruction and sneezing, and 80% for nasal discharge. Complaints about vasomotor rhinitis increased up to a severity near the pretreatment level in eight patients on the 180th postoperative day and the procedure was repeated.

Conclusion: These findings indicate that radiofrequency may be used as an alternative treatment option in patients with vasomotor rhinitis.
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June 2008

Atopy in patients with bronchiectasis: more than coincidence.

Tohoku J Exp Med 2006 Jan;208(1):41-8

Department of Allergic Diseases, Gulhane Military Medical Academy, Ankara, Turkey.

Bronchiectasis is common in developing countries, but its precise underlying mechanism can be detected in only about 40% of the cases. The studies reporting the frequency of atopy and its relation to radiological findings and lung function in bronchiectasis are limited in number, and the results are controversial. The present study was designed to investigate the relationship between atopy and bronchiectasis by means of high resolution computed tomography (HRCT) and pulmonary function tests. Skin prick test, HRCT and pulmonary function tests, including spirometric values of forced expiratory volume in one second (FEV1), FEV1/FVC (forced vital capacity) ratio were performed in 121 bronchiectatic patients of unknown etiology and in 68 healthy controls. Atopy and HRCT scores for the severity of atopy and extent of bronchiectasis respectively were determined for each patient. The rate of atopy (48.8% vs 11.8%) and mean atopy score (14.3 +/- 10.1 mm vs 5.5 +/- 2.1 mm) were significantly higher in patients with bronchiectasis than those in controls. Atopic patients had significantly worse spirometric values and more extended bronchiectasis than non-atopics. There is a significant correlation between atopy and HRCT scores (r = 0.54, p < 0.001), indicating that the more severe atopy is the more extended bronchiectasis. In conclusion, we suggest that the rate of atopy is higher in bronchiectatic patients than that in healthy controls. Bronchiectatic patients with atopy have lower spirometric values and higher HRCT scores. Atopy might be considered as a deteriorating and/or a causative or contributing factor for development of bronchiectasis.
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January 2006

Electrophoretic evaluation of nasal discharge in patients with allergic rhinitis and vasomotor rhinitis.

Am J Rhinol 2002 May-Jun;16(3):141-4

Department of Otorhinolaryngology and Head and Neck Surgery, Gülhane Medical School, Etlik, Ankara, Turkey.

Background: Allergic rhinitis and vasomotor rhinitis are two common diseases that have similar symptoms and physical findings. This study was designed to assess the efficacy of electrophoretic analysis of nasal discharge for the differential diagnosis of allergic rhinitis and vasomotor rhinitis.

Methods: Two different groups of patients with allergic rhinitis (n = 18) and with vasomotor rhinitis (n = 18) diagnosed by current methods and 10 healthy subjects as a control group were included in this study. Component analyses of proteins in nasal wash were made by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Results: The mean levels of total protein, 66-kDa proteins and 26-kDa proteins (277.2 +/- 9 microg/mL, 114.5 +/- 9 microg/mL, and 67.0 +/- 4 microg/mL, respectively), in nasal washing samples of patients with allergic rhinitis were found to be higher than in the samples, (222.0 +/- 6 microg/mL, 65.6 +/- 6 microg/mL, and 42.9 +/- 4 microg/mL respectively) obtained from patients with vasomotor rhinitis. The control group showed the lowest rate of these proteins (167.8 +/- 7 microg/mL 34.3 +/- 3 microg/mL, and 25.0 +/- 3 microg/mL, respectively). The differences between mean levels of these proteins in all groups were statistically significant (p < 0.05).

Conclusions: These findings indicate that electrophoretic analysis of nasal discharge can be used for the diagnosis of allergic rhinitis and vasomotor rhinitis. However, further studies are needed to standardize the technique of nasal wash and to determine the range of proteins in nasal secretions that will confirm the diagnosis.
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January 2003