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Allergic Diseases as a Clinical Phenotype Marker in Patients with Common Variable Immunodeficiency
(Karger, 2023) Yildiz, Eray; Colkesen, Fatih; Arslan, Sevket; Evcen, Recep; Aykan, Filiz Sadi; Kilinc, Mehmet
Introduction: Patients with common variable immunodeficiency (CVID) have been shown to be more predisposed to develop allergic diseases because of mucosal immune defects and immune dysregulation. The aim of this study was to determine the prevalence, and clinical and laboratory characteristics of various allergic diseases in patients with CVID. Methods: The study included patients aged & GE;18 years who were followed up for a diagnosis of CVID. Patients were separated into 5 groups according to the clinical phenotypic characteristics of lymphoproliferation, autoimmunity, gastrointestinal diseases, allergic diseases, and malignancy. Atopic dermatitis (AD), drug hypersensitivity reaction (DHR), allergic rhinitis (AR), and asthma were accepted as allergic diseases. Results: The most commonly seen clinical phenotypes were lymphoproliferation in 41 (48.8%) patients and allergic diseases in 31 (37%). AD was determined in 2 (2.4%) patient, DHR in 5 (6%), AR in 7 (8.3%), and asthma in 21 (25%). The delay in diagnosis of patients with allergic disease was determined to be shorter compared to those without allergic disease (p = 0.042). Serum total immunoglobulin E level, CD19(+) B cell, switched memory B cell, and natural killer cell counts were determined to be higher in the CVID patients with allergic disease compared to those without (p = 0.007, p = 0.022, p = 0.023, p = 0.017, respectively). Conclusion: Allergic diseases should be considered as a marker of clinical phenotype in CVID because of the clinical and immunological differences. Early diagnosis and treatment of allergic diseases in patients with CVID can improve quality of life.
Allergic diseases in the elderly population: a single-center experience
(Tubitak Scientific & Technological Research Council Turkey, 2021) Yildiz, Eray; Colkesen, Fatih; Arslan, Sevket; Evcen, Recep; Sadi Aykan, Filiz; Kilinc, Mehmet; Aytekin, Gokhan
Background/aim: Although allergic diseases are generally considered to be diseases of childhood and youth, the first symptoms of allergic diseases can be seen in old age sometimes. The aim of this study was to determine the prevalence and characteristics of allergic diseases in the elderly population admitted to the allergy unit on an outpatient basis. Materials and methods: The files of the patients who applied to our clinic's allergy unit during the 8-year period were retrospectively analyzed. The data of patients aged >_ 65 years were obtained from the files of our allergy unit archive. Results: A total of 1272 patients aged >_ 65 years old were included in the study. The mean age was 70 years (range: 65-97 years). Most of the patients were female (n = 704, 55.3%). Of the patients, 887 (69.8%) presented with cutaneous symptoms, and urticaria was identified in 500 of them (56.3%). Drug hypersensitivity reactions were detected in 175 (13.7%) patients. A total of 71 (5.6%) patients had asthma, 65 (5.1%) had anaphylaxis, 48 (3.8%) had allergic rhinitis, 24 (1.9%) had hymenoptera venom allergy, and 18 (1.4%) had food allergies. Atopy history (OR = 2.323, 95% CI = 1.590-3.393, p < 0.001) and comorbidity (OR = 1.631, 95% CI = 1.050-2.533, p = 0.029) were found to be risk factors for drug hypersensitivity reactions. Male sex (OR = 3.462, 95% CI = 1.097-10.933, p = 0.034) and atopy history (OR = 14.877, 95% CI = 6.081-36.393, p < 0.001) were found to be risk factors for hymenoptera venom allergy. Conclusion: Diagnosis becomes difficult due to the perception that allergic diseases mainly affect young people. Clinical symptoms are not evident in the elderly and age-related difficulties are encountered in diagnostic tests. There is a need to develop specific guidelines for the diagnosis of allergic diseases in the elderly.
Anaphylaxis in older adult patients: a 10-year retrospective experience
(Elsevier, 2022) Yildiz, Eray; Arslan, Sevket; Coelkesen, Fatih; Evcen, Recep; Aykan, Filiz Sadi; Kilinc, Mehmet
Background: Despite the worldwide increase in life expectancy and the elderly population, very little is known about the characteristics of anaphylaxis in older adults.Methods: A retrospective scan was made of the files of patients who presented at the Allergy Unit of our clinic between October 2011 and October 2021. The study included 971 patients aged >18 years who met the criteria for diagnosis of anaphylaxis. The patients were separated into 2 groups of adults (18-64 years) and older adults (>65 years).Results: The adult group included 887 (91.3%) patients and the older adult group, 84 (8.7%) patients. Comorbid diseases were seen more frequently in the older adults than in the adult group (p < 0.001). Drugs were seen to be the most common trigger of anaphylaxis in both groups, and this was more common in the older adult group (p = 0.039). Food was a more common trigger of anaphylaxis in the adult group than in the older adult group (p = 0.017). In both groups, the skin was the organ most affected, and was less affected in the older adults than in the adults (p = 0.020). Cardiovascular symptoms were seen significantly more and respiratory symptoms significantly less in the older adult group (p < 0.001, p = 0.002, respectively). Admission to the hospital and the intensive care unit was more frequent in the older adult group and rates of adrenalin administration were higher compared to the adult group (p < 0.001 for all).Conclusion: Anaphylaxis in the older adults is generally caused by drugs. Older adults were found to have more cardiovascular symptoms and more frequent adrenalin injections, hospitalizations and intensive care unit admissions.
An association between immune status and chest CT scores in COVID-19 patients
(Wiley, 2021) Colkesen, Fatih; Poyraz, Necdet; Arslan, Sevket; Yilmaz, Pinar Diydem; Kurt, Esma Kepenek; Korkmaz, Celalettin; Yildiz, Eray
Background The characteristic features of the immune responses of COVID-19 patients and how they reflect lung involvement have not been clearly elucidated. Aim The aim of this study was to examine the immune status and the correlations thereof with chest CT scores and lung involvement of patients with COVID-19. Methods In this retrospective and single-center study, 72 patients with laboratory-confirmed COVID-19 were recruited. The counts of peripheral lymphocyte subsets (CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, CD19(+) B cells and CD16(+) 56(+) NK cells) and those of serum immunoglobulins (IgA, IgG, IgM) were measured and their associations with chest CT scores analysed. Results The proportions of lymphopenia in patients with extensive lung involvement were twice that in the general study population. In the severe disease group, the levels of total lymphocytes, T cells, B cells, NK cells; and serum IgA levels, were significantly lower than in the mild disease group (all P < .05). We found that the numbers of lymphocyte subsets and the IgA level negatively correlated with the chest CT scores. On multivariate regression analysis, pretreatment decreases in total lymphocytes, CD3(+) T cells, CD4(+) T cells, and CD19(+) B cells, and serum IgA levels, were independent predictors of severe lung involvement. Conclusions The cell numbers of peripheral lymphocyte subsets and the serum IgA level were negatively correlated with the chest CT scores in COVID-19 patients. These parameters tended to independently predict severe lung involvement in such patients.
Evaluation of malnutrition risk and nutrition status in adult patients with common variable immunodeficiency
(Wiley, 2022) Yildiz, Eray; Arslan, Sevket; Colkesen, Fatih; Aykan, Filiz Sadi; Evcen, Recep; Kilinc, Mehmet; Aytekin, Gokhan
Background The aim of this study is to determine the prevalence of malnutrition in outpatients with common variable immunodeficiency (CVID) and the utility of nutrition screening tools to detect malnutrition in these patients. Methods Fifty outpatients with CVID were included in the study. Nutrition risk for each patient was evaluated using four nutrition screening tools: Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Short Nutritional Assessment Questionnaire (SNAQ), and Nutritional Risk Screening 2002 (NRS-2002). Results According to MUST, MST, SNAQ, and NRS-2002, malnutrition risk was determined to be 48% (n = 24), 26% (n = 13), 20% (n = 10), and 20% (n = 10), respectively. Malnutrition was detected in 54% (n = 27) of the patients. It was found that MUST showed a better correlation in detecting malnutrition in outpatients with CVID (kappa = 0.482, P = 0.001). MUST has a higher positive and negative predictive value than other nutrition screening tools (79% and 70%, respectively). In the multivariate logistic regression analysis, it was found that low serum immunoglobulin A (IgA) levels at diagnosis increased the risk of malnutrition by similar to 15 times, and low CD19(+) B-cell counts increased the risk by approximately eight times. Conclusion The prevalence of malnutrition in patients with CVID was found to be quite high, and there was a strong correlation between malnutrition and low CD19(+) B-cell counts and low serum IgA levels. Given the high rate of malnutrition in patients with CVID, nutrition assessment is recommended rather than starting with nutrition screening.
Evaluation of the Effectiveness of the 6 Warning Signs of the European Society for Immunodeficiencies for Primary Immunodeficiencies in Older Adults
(Karger, 2024) Yildiz, Eray; Colkesen, Fatih; Evcen, Recep; Aykan, Filiz Sadi; Kilinc, Mehmet; Arslan, Sevket
Introduction: Diagnostic delay in cases of primary immunodeficiency (PID) is a significant problem for clinicians, and most do not have sufficient awareness of this uncommon disorder. The European Society for Immunodeficiencies (ESID) has developed 6 warning signs to increase awareness of adult PIDs. The aim of this study was to determine the prevalence of PID in older adults regardless of the reason for presentation and to evaluate the effectiveness of the 6 warning signs of ESID in the diagnosis of PIDs. Methods: The study included 1,331 patients aged >= 65 years who presented at our clinic for any reason and were questioned about the ESID 6 warning signs for PIDs. After the exclusion of reasons for secondary immunodeficiency (SID), all the patients underwent immunological evaluation for the diagnosis of potential underlying PIDs. Results: After excluding 6 patients diagnosed with SID, PID was diagnosed in 16 (1.2%) of 1,325 older adults using ESID warning signs. The most common reasons for presentation were infection (69%) in the PID group and urticaria and/or angioedema (41.5%) in the non-PID group. The most common PID subgroup was common variable immunodeficiency (50%). In 12 of the patients diagnosed with PID, there was at least 1 positive ESID warning sign. In 4 patients, PID was determined despite negative ESID warning signs. The patients diagnosed with PID showed a significant, minimal level of agreement with questions 1 and 4 of the ESID warning signs (p < 0.001, kappa = 0.204, p = 0.005, kappa = 0.208, respectively). Conclusion: The ESID warning signs do not encompass all the symptoms and findings of PIDs. There is a need for more infection-centered questions to determine PIDs in older adults. Therefore, the ESID warning signs should be further developed.
Increasing Prevalence of Sensitization to Cat/Dog Allergens in the COVID-19 Pandemic
(Karger, 2024) Evcen, Recep; Colkesen, Fatih; Yildiz, Eray; Aykan, Filiz Sadi; Kilinc, Mehmet; Akkus, Fatma Arzu; Arslan, Sevket
Introduction: Cat and dog allergens are common indoor triggers for respiratory allergies such as allergic rhinitis and asthma. This study aims to evaluate the prevalence of cat and dog allergies in adults and analyze changes during the COVID-19 pandemic.Methods: We retrospectively analyzed the medical records of 8,102 patients who visited an allergy clinic and underwent skin prick testing (SPT) from March 2018 to March 2022: 2 years before and 2 years during the pandemic. Demographic information, clinical attributes, and laboratory results were examined based on patient records.Results: Of 8,102 SPTs performed, 400 (4.9%) were sensitized to cat allergen and 289 (3.6%) to dog allergen. Allergic rhinitis was the predominant clinical diagnosis in both groups. Of the 400 subjects exposed to cats, 240 (60%) experienced allergic symptoms, while of the 289 subjects exposed to dogs, 65 (22.5%) experienced allergic symptoms during exposure. Within the cat-sensitized group, anaphylaxis was observed in 5 patients (1.3%), while no cases of anaphylaxis were reported in the dog-sensitized group. Compared to the pre-pandemic period, patients presenting during the pandemic had higher rates of cat and dog sensitization (5.7% vs. 4.1%; p < 0.05, 5.2% vs. 1.7%; p < 0.05).Conclusion: During the COVID-19 pandemic, there was an increase in cat and dog allergies among adults. Increased exposure to pet antigens, both directly and indirectly, has resulted in more people becoming sensitized to cats or dogs.
Is common variable immunodeficiency a facilitating factor for fixed drug eruptions? Case Report
(Wiley, 2020) Yildiz, Eray; Arslan, Sevket; Colkesen, Fatih; Aytekin, Gokhan
[Abstract Not Availabe]
Memory B cells and serum immunoglobulins are associated with disease severity and mortality in patients with COVID-19
(Oxford Univ Press, 2022) Colkesen, Fatih; Kepenek Kurt, Esma; Vatansev, Hulya; Korkmaz, Celalettin; Colkesen, Fatma; Yucel, Fatih; Yildiz, Eray
Purpose of the study The aim of this study was to investigate the relationship of B cell-mediated immunity with disease severity and mortality in patients with COVID-19. Study design In this retrospective cohort and single-centre study, 208 patients with laboratory-confirmed COVID-19 were recruited. A COVID-19 severity score, ranging from 0 to 10, was used to evaluate associations between various factors. Serum immunoglobulin levels and the number of cells in B lymphocyte subsets were measured and their association with disease severity and mortality in patients with COVID-19 examined. Results The median age of the patients was 50 (35-63) years and 88 (42%) were female. The number of deceased patients was 17. The median COVID-19 severity score was 8 (6-8) in deceased patients and 1 (0-2) in survivors. Deceased patients had significantly lower levels of total B lymphocytes, naive B cells, switched memory B cells, and serum IgA, IgG, IgG(1) and IgG(2) than recovered patients (all p<0.05). In addition, a significant negative correlation was found between the number of these parameters and COVID-19 severity scores. Decrease in the number of total B cells and switched memory B cells as well as lower serum IgA, IgG and IgG(1) levels were independent risk factors for mortality in patients with COVID-19. Conclusion In the present study, the prognosis of patients with COVID-19 was shown to be associated with the B cell subset and serum immunoglobulin levels.
Nephrological factors may cause kidney dysfunction in patients with common variable immunodeficiency
(Tubitak Scientific & Technological Research Council Turkey, 2021) AytekIn, Gokhan; Baloglu, Ismail; Colkesen, Fatih; Yildiz, Eray; Arslan, Sevket; Turkmen, Kultigin
Background/aim: Common variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, an increased risk of autoimmune disease, malignancy, and chronic inflammation. Proteinuria is one of the most important prognostic factors causing progression in kidney disease. Proteinuria causes tubulotoxicity, activates inflammatory markers that cause fibrosis, and consequently nephropathy progression. The data is scant in the literature regarding the inflammation and nephropathy in CVID. Hence, in the present study, we aimed to investigate the relationship between tubular dysfunction, proteinuria, and inflammation in patients with CVID. Materials and methods: This was a cross-sectional study involving 27 patients with CVID (15 females, 12 males; mean age, 39.88 +/- 13.47 years) and 18 control subjects (10 females, 8 males; mean age, 33.83 +/- 7.97 years). Patients were evaluated for kidney functions including glomerular filtration rate, fractional excretion of sodium, metabolic acidosis, serum/urine anion gap, 24-h urine proteinuria and, were grouped in terms of proteinuria. Blood samples obtained from the patients with CVID were taken into 2 mL EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD 8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique. Results: Urinary density, fractional excretion of sodium, proteinuria, and metabolic acidosis are found to be higher in patients with CVID when compared to healthy controls. In the bivariate correlation analysis, proteinuria was positively correlated with age (r = 0.496, p = < 0.001), CD8+T cells percentage (r = 0.427, p = 0.02). Albumin, CRP, and CD8+T cell percentage were found to be independent variables of proteinuria. Conclusion: Increased chronic ongoing inflammation was found to be associated with proteinuria in patients with CVID. Hence, in routine outpatient clinics, proteinuria should not be overlooked in this group of patients.
Poor Sleep Quality and Associated Factors in Patients with Common Variable Immunodeficiency
(Galenos Publ House, 2022) Yildiz, Eray; Arslan, Sevket; Yildiz, Buket Tugan; Berktas, Deniz Tuncel; Colkesen, Fatih; Evcen, Recep; Aykan, Filiz Sadi
Objective: This study aimed to examine the sleep quality of common variable immunodeficiency (CVID) patients and to investigate the relationship between sleep quality and depression, anxiety, fatigue, excessive daytime sleepiness and naturel killer (NK) cell counts. Materials and Methods: The study included 53 patients followed with CVID diagnosis. To determine sleep quality and conditions associated with sleep quality in CVID patients, Pittsburgh sleep quality index (PSQI), fatigue severity scale (FSS), Hamilton depression scale (HAM-D), Hamilton anxiety scale (HAM-A) and Epworth sleepiness scale (ESS) were used. Results: Fatigue was found in 37 (70%) patients, poor sleep quality in 34 (64%), depression in 20 (38%), anxiety in 16 (30%), and excessive daytime sleepiness in 11 (21%) patients. All patients CVID patients received immunoglobulin replacement therapy: Intravenous immunoglobulin (IVIG) in 37 (72%) and subcutaneous immunoglobulin (SCIG) in 16 (28%) patients. The PSQI, HAM-A, HAM-D and FSS scores of the patients receiving IVIG treatment were higher than those of the patients receiving SCIG treatment (all, p<0.05). According to the multivariate logistic regression analysis, lower NK cell counts [odds ratio (OR) =13.384, 95% confidence interval (CI)= 2.478-72.284, p=0.003] and depression (OR=7.030, 95% CI=1.320-37.435, p=0.022) were risk factors for poor sleep quality. Conclusion: Our results showed that patients with CVID had a higher frequency of poor sleep quality, depression, anxiety, fatigue, and excessive daytime sleepiness than the general population. Therefore, sleep quality and mental status should be questioned in detail during routine control in patients with CVID.
Relationship between Selective IgA Deficiency and COVID-19 Prognosis
(Natl Inst Infectious Diseases, 2022) Colkesen, Fatih; Kandemir, Bahar; Arslan, Sevket; Colkesen, Fatma; Yildiz, Eray; Korkmaz, Celalettin; Vatansev, Hulya
The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry into the body. Immunoglobulin A (IgA) is the primary antibody responsible for mucosal immunity. We explored the relationship between selective IgA deficiency (SIgAD) and COVID-19 severity. We included 424 patients (203 women) with COVID-19. Eleven patients had SIgAD. Laboratory data of patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored using logistic regression analysis. In the univariate logistic regression analysis, the risk of severe COVID-19 disease in patients with SIgAD was approximately 7.7 -fold higher than that in other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, P = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, P = 0.026) higher in the multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts and negatively correlated with C-reactive protein levels, which was a risk factor for severe COVID-19. In patients with SIgAD, the number of severe acute respiratory coronaviruses 2 that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.

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