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Purpose: To evaluate serum 25-hydroxyvitamin D [25(OH)D3] levels of vernal keratoconjunctivitis (VKC) children.Methods: A total of 62 non-atopic healthy children (64.5% male, mean age 10.79 ± 3.3 years) and 29 VKC children (75.9%, mean age 12.17 ± 2.7 years) were included in the study. Serum 25(OH)D3 levels measured by HPLC were compared between the two groups and a p value of <0.05 was considered as statistically significant.Results: The mean serum 25(OH)D3 level of VKC group was significantly lower than in the control group (11.02 ± 5.16 ng/mL and 15.99 ± 7.36 ng/mL, respectively) (p = 0.002). Severe vitamin D deficiency (<10 ng/mL) was detected in 48.3% of VKC children and 22.6% of the controls (p = 0.017). Time spent outdoors during daylight was higher in the control group (229.5 ± 101.2 min) compared with the VKC group (160.7 ± 65.9 min) (p = 0.008), and showed a significant correlation with serum 25(OH)D3 levels (Spearman rho = 0.812) (p<0.001).Conclusions: Children with VKC should be evaluated for vitamin D deficiency, which might occur secondary to sun avoidance. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the role of the CD19 complex in the pathogenesis of transient hypogammaglobulinemia of infancy (THI) and to better characterize the subsets of memory B cells. The study population consisted of 22 male and 14 female patients with a mean age at presentation of 20 ± 9.9 months. The CD19 complex and B cell subsets were evaluated by flow cytometry. While the CD19 median fluorescence index (MFI) in patients with THI was significantly lower than controls (122.9 ± 66.7 in patients; 184.2 ± 39 in controls, p < 0.01), expression of CD21 and CD81 was increased (94.4 ± 3, 96.8 ± 2.5 % in patients; 91 ± 3.9; 94.7 ± 3.5 % in controls, p < 0.01 vs. p < 0.05, respectively). The expressions of switched memory B cells and IgM memory B cells were found to be reduced in THI. Considering that the CD19 complex regulates the events following antigen stimulation, the change in CD19 complex detected in THI may be related to insufficiency of antibody production. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence of systemic atopy and immunoglobulin (Ig) deficiencies in vernal keratoconjunctivitis (VKC). Methods: Sixty-seven VKC subjects (79.1% boys) with a mean age of 11.3 ± 4.3 years were included. Serum Ig levels and specific IgE levels were measured using the nephelometric method and reversed enzyme immunoassay with sandwich ELISA technique, respectively. The patients underwent epidermal skin tests with commercial extracts. Results: Family history of atopy and associated systemic allergies were detected in 32.8 and 40.3% of the subjects, respectively. Blood eosinophilia, elevated total, and specific IgE and positive skin tests were detected in 33.8, 42.2, 50, and 35% of the subjects, respectively. Out of 62 subjects, low levels of IgA, IgG, IgM, and IgG3 were detected in 12.9, 8, 6.5, and 1.6% of the patients, respectively. Conclusion: IgE-mediated mechanisms are involved in approximately 40% of VKC patients. A new finding was the higher incidence of Ig deficiency. [ABSTRACT FROM AUTHOR]

Focal epithelial hyperplasia, also known as Heck's disease, is a rare but distinctive entity of viral etiology with characteristic clinical and histopathological features. It is a benign, asymptomatic disease of the oral mucosa caused by human papilloma viruses (HPV). Previous studies postulated an association between these lesions and immunodeficiency. Genetic deficiency of adenosine deaminase (ADA) results in varying degrees of immunodeficiency, including neonatal onset severe combined immunodeficiency (ADA-SCID), and milder, later onset immunodeficiency. We report a 12-year-old girl with the late onset-ADA deficiency presenting with Heck's disease. Our case report should draw attention to the possibility of immunodeficiency in patients with HPV-induced focal epithelial hyperplasia. [ABSTRACT FROM AUTHOR]

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin (Ig) levels. Usually, this clinical picture resolves spontaneously by 3 yr of age. However, hypogammaglobulinemia persists until adolescence in some patients. In recent years, those patients have been classified as undefined/unclassified hypogammaglobulinemia (UCH). We aimed to evaluate the clinical and immunologic features of patients with THI and UCH considering age of recovery and to assess relationships between hypogammaglobulinemia, infections, and allergic manifestations. We reviewed the medical records of children followed with a diagnosis of hypogammaglobulinemia from 2001 to 2007. Patients with decreased levels (<2 s.d.) of one or more major Ig isotypes (IgG, IgA, IgM) with normal antibody responses and lymphocyte subpopulations were included (n = 374). Those patients whose Igs normalized during the follow-up period were classified as THI and the others as UCH. The THI group consisted of 71 patients (27 females, 44 males) with a mean recovery age of 68.87 ± 36.5 months. About 95% of patients with THI recovered before 10 yr of age. The UCH group consisted of 303 patients (105 females, 198 males) with a mean age at diagnosis of 52 ± 42 months. The most common presenting manifestations in the THI and UCH groups were upper respiratory tract infections (URTIs), lower respiratory tract infections, and asthma (42%, 50%, and 52% in the THI group vs. 39%, 53%, and 55% in the UCH group, respectively). In the THI group, the prevalence of atopic disease was related to age and found to be increased markedly after 44 months. In all patients, the prevalence of asthma was independently and positively associated with family history of atopy and age, whereas it was negatively associated with recurrent URTIs. Patients with THI and UCH have similar clinical and immunologic features. The normalization of Igs may be delayed in a majority of the patients with hypogammaglobulinemia. This observation may be a contribution to the classical definition and diagnostic criteria for THI. [ABSTRACT FROM AUTHOR]

Although the presence of physiologic anti-CD95 (Fas, APO-1) autoantibodies in intravenous immunoglobulin (IVIG) preparations is known, the effects of these antibodies in patients with common variable immunodeficiency are unclear (CVID). The aim of the study was to assess the effects of IVIG in Fas expression, activation markers and the subsets of T cells in patients with CVID. We studied 15 cases with CVID and 10 healthy controls with no signs of immunodeficiency. The Fas expression of T cells, activation markers (CD25, CD69 and HLA-DR) and T-cell subsets were analyzed by four-color flow cytometry. We found that the Fas expression of CD3+ T cells in patients was significantly higher than in controls. In addition, there was a significant increase in the Fas expression of CD3+ T cells and CD4+ T cells, and the CD25 expression of CD3+ and CD4+ T cells after IVIG supplementation ( P < 0.05). The CD69 and HLA-DR expressions of T cells and CD8+ T cells were not affected by IVIG infusion. Our observation showed that IVIG replacement causes an increase in the Fas and CD25 expressions in patients with CVID. These data suggest that the Fas protein may have an important role in the effects of IVIG for the control of autoimmunity in patients with CVID, as well as in the generation of autoimmune disease. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is a disorder characterized by hypogammaglobulinemia, poor antibody responses and recurrent bacterial infections. CVID patients have a higher prevalence of autoimmune disease and some of them develop noncaseating granulomas of the lungs, spleen, liver, skin, lymph nodes and eye. We report herein a 5-year-old girl with CVID presented with cutaneous nodules, granulomatous uveitis and oligoarthritis. The lesions, arthritis and uveitis responded well to treatment with the systemic administration of steroid. Different autoimmune diseases could be seen together in children with CVID. These patients require therapeutic cooperation of the immunologists with different specialists, including dermatologists, rheumatologists and ophthalmologists. [ABSTRACT FROM AUTHOR]

Aim: Primary immunodeficiencies (PIDs) are a heterogeneous disorder group characterized by an impaired immune system, leading to an increased susceptibility to infections and a wide range of clinical manifestations, including gastrointestinal (GI) complications. This study aimed to assess the GI manifestations of PID patients and highlight the significance of atypical gastrointestinal symptoms in the early diagnosis of these patients. Methods: A retrospective analysis was conducted on pediatric patients diagnosed with PIDs at Selcuk University Medical Faculty from 2011 to 2021. The study focused on demographic data, clinical presentation, genetic mutations, and GI manifestations, including endoscopic evaluation. Patients were categorized according to the International Union of Immunological Societies (IUIS) PID classifications. Statistical analyses were performed to identify significant associations between PID types and GI manifestations. Results: The cohort comprised 101 patients, with 46% presenting with GI symptoms, including malnutrition and chronic diarrhea, as the most common findings. Primary antibody deficiency (PAD) emerged as the most prevalent PID with GI involvement, followed by combined immunodeficiencies (CID) with associated or syndromic features. Endoscopic evaluations revealed inflammatory bowel disease (IBD)-like colitis in a significant subgroup of patients. The analysis showed that some GI symptoms were more common in specific PID categories, highlighting the importance of early gastroenterological assessment in PID patients. Conclusion: Recognition of common GI symptoms in pediatric patients with PIDs may facilitate early diagnosis and prompt multidisciplinary management, potentially improving patient outcomes. The study highlights the necessity of considering PIDs in diagnosing persistent or severe GI symptoms in children. [ABSTRACT FROM AUTHOR]

Purine nucleoside phosphorylase (PNP) deficiency is a rare immunodeficiency syndrome generally characterized by profound T cell deficiency and variable B cell function. More than half of PNP-deficient patients present with neurological dysfunction, with manifestations such as mental and motor retardation, spasticity, hypertonia, ataxia, and behavioral disturbances. Here, we report two siblings diagnosed with PNP deficiency in early infancy. Our patients had developmental delays, and their immunological findings indicated T-B+NK+ leaky/atypical severe combined immune deficiency. The patients are being treated with regular intravenous immunoglobulin replacement, as well as trimethoprim-sulfomethoxazole and fluconazole, for prophylaxis in preparation for transplantation. These cases draw attention to the possibility of primary immune deficiency in patients with recurrent infections and lymphopenia. In addition, PNP deficiency should be kept in mind in the presence of developmental delay, low uric acid levels, and lymphopenia. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer‐related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non‐small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min‐max) = 64.03 (45–83); 20 stage I–III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD‐1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD‐1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC. [ABSTRACT FROM AUTHOR]

Juvenile rheumatoid arthritis (JRA) is a complex disease involving the interactions of several cell populations with different mediators. Herein, we report a five-year-old girl with systemic-onset JRA. At admission, peripheral blood flowcytometric analysis showed the percentages of CD19+ and CD20+ B cells were <1%. These values returned to normal on the tenth day of steroid treatment. This is the first report of JRA presented with absence of B lymphocytes in the literature and suggested that lymphocytes subset analysis could change with treatment in patients with JRA. Different clinical signs and symptoms reflecting aspects of JRA are critical for the etiology of the disease and to identify new strategies for treatment. [ABSTRACT FROM AUTHOR]

Chilaiditi syndrome is the interposition of the colon between the diaphragma and the liver. In general, patients are asymptomatic, but some patients have been associated with gastrointestinal and respiratory symptoms. A 5-month-old infant boy was admitted to the hospital with a history of cough, cyanosis and recurrent respiratory distress that had persisted during the preceding 2 months. The chest X-ray revealed an elevation of the right hemidiaphragma caused by the presence of a dilated colonic loop below. Computed tomography showed a hepatodiaphragmatic interposition of the colon, leading to the diagnosis of Chilaiditi syndrome. The patient was conservatively treated with oxygen, fluid supplementation and stool softeners. We conclude that this rare syndrome should be kept in mind when young patients present with recurrent respiratory distress. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory benign breast disease. Although the etiology of this disease is unknown, it has been suggested that hormonal disorders, autoimmunity, smoking, and α1-antitrypsin deficiency may play a role in the etiopathogenesis. The aim is to investigate the changes in cytokine profiles including interleukin (IL)-4, -8, -10, -17, and tumor necrosis factor (TNF)-alpha in patients with IGM. Methods: Forty-seven patients with pathologically diagnosed IGM and 30 healthy women were included. The cytokines including IL-4, -8, 10, -17, and TNF-alpha were measured by human enzyme-linked immunosorbent assay. Results: The IL-8, IL-10, and IL-17 levels were higher in IGM patients than control group (p =.002; p =.008; and p =.018, respectively). The IL-8 levels of patients with active lesions and in remission were statistically higher than the control group (p =.027 and p =.015, respectively). IL-10 levels of patients in remission were higher than the control group (p =.024). There was no difference in IL-4 and TNF-ɑ levels between all groups. Conclusion: These results showed that proinflammatory cytokines including IL-8 and IL-17 have role in pathogenesis of IGM. However, the increased levels of IL-10 in especially patients in remission suggest that it reduces the release of proinflamatory cytokines as well as suppressing their function and activation for controlling IGM. Although IGM is thought to be a surgical disease, these cytokine changes indicate the presence of serious immune dysregulation. This suggests that in the treatment of IGM, treatment needs to evolve from surgery to medical treatment. Key points • The IL-8, IL-10, and IL-17 levels were higher in IGM patients than in control group. • The IL-8 levels of both patients with active lesions and in remission were high. • There was no difference in IL-4 and TNF-ɑ levels between all groups. [ABSTRACT FROM AUTHOR]

Objective: Although there has been increased attention in recent years to the relationship between allergic disease and obesity, there is limited information about allergic rhinitis (AR) and central obesity. The aim of this study is to investigate the relationship between central obesity and rhinitis severity in patients with rhinitis and controls. Materials and Methods: A total of 164 children, aged 7-17 years, were included in the study between 2020 and 2021. Three groups were formed: AR, non-allergic rhinitis (NAR), and the control group. The height, weight, waist, hip, neck, and arm circumference of the groups were measured. The BMI, waist-to-hip ratio, waist-to-height ratio, and conicity index were calculated. Eosinophil and neutrophil counts, IgE levels, and allergic sensitization were recorded. Anthropometric measurements, rhinitis severity, and persistence were compared among the groups. Results: The study included a total of 164 children: 63 with AR, 51 with NAR, and 50 in the control groups of the children included in the study, 71 (43.3%) were boys, and 93 (56.7%) were girls. Approximately 30% of children with normal BMI were evaluated as centrally obese despite having a normal weight. Rhinitis patients had a higher prevalence of central obesity compared to the control group. When comparing both persistence and disease severity, central obesity was higher in AR patients than in NAR patients. The AR group had higher BMI, arm circumference, waist circumference, and neck circumference than the control group (p=0.003, p=0.01, 0.001, 0.004, respectively), while the waist-to-height ratio was higher in both the AR and NAR groups compared to the control group (p=0.001, p=0.026). Conclusion: In this study, central obesity was significantly higher in patients with AR and NAR than in the control group although there was no significant difference in obesity between the groups according to BMI. Additionally, centrally obese AR patients exhibited higher persistence and disease severity compared to NAR patients. In conclusion, other obesity indicators such as waist circumference should be measured in addition to height and body weight in children with AR and NAR. [ABSTRACT FROM AUTHOR]

Infection of the eyelids confined to the preseptal space is relatively common but potentially serious. We report a child with cutaneous anthrax to remind that the interesting contagious cause be included in the differential diagnosis of the preseptal cellulitis. [ABSTRACT FROM AUTHOR]

Although congenital defects of diaphragma often occur in the period immediately following birth, 10-20% of these cases are diagnosed later. We report on a 7-month-old male infant with late-presenting congenital diaphragmatic hernia associated with a thoracic ectopic kidney. We conclude that congenital diaphragmatic defects should be considered in young children with respiratory distress and that computerized tomography is a noninvasive and accurate diagnostic method in the evaluation of additional abnormalities in these patients. [ABSTRACT FROM AUTHOR]

Background: Seeds are widely consumed as a traditional snack and have rich contents beneficial to health. With an increase in consumption rates, allergic reactions occur more frequently. We focus on multiple seed consumption related to recurrent anaphylaxis in this case. Case Presentation: We evaluated an 11-year-old boy with recurrent anaphylaxis. According to his medical records, he had been hospitalized several times, diagnosed with anaphylaxis, and treated. The family noticed direct (eating) or indirect contact with pumpkin seeds. In addition, the family mentioned another anaphylactic episode after watermelon seed and poppy seed bread consumption. We conducted skin prick-to-prick tests, examined total immunoglobulin E levels, and prescribed the treatment with an adrenalin autoinjector and preventive dietary recommendations. Conclusion: Anaphylaxis, particularly recurrent ones, should be evaluated with detailed anamnesis and supported with laboratory tests. Although seeds are beneficial and highly nutritious, it is necessary to consider them a source of allergens. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 3-month-old patient with congenital non-bullous ichthyosiform erythroderma, initially misdiagnosed as Omenn syndrome but later identified with Desmoglein-1 (DSG1) deficiency. Topics discussed include the diagnostic process, the clinical features distinguishing DSG1 deficiency from Omenn syndrome, and the treatment approach including immunoglobulin replacement therapy and retinoid treatment.

We report a patient with a double novel mutation in the BTK gene, who presented with skin abscesses caused by Pseudomonas aeruginosa. Despite antimicrobial therapy and multiple debridements due to relapse, the abscesses and subcutaneous nodules had to be evacuated by plastic surgery and the wounds were dressed daily with dressings containing silver. [Extracted from the article]

Monocytes are one of the principal immune defense cells that encounter infectious agents. However, an essential role of monocytes has been shown in the spread of viruses throughout the human body. Considering this dilemma, this study aimed to evaluate monocyte subsets and Human Leukocyte Antigen–DR isotype (HLA-DR) expressions in clinical coronavirus disease 2019 (COVID-19) cases. This prospective, multicenter, case–control study was conducted with COVID-19 patients and healthy controls. The patient group was divided into two subgroups according to disease severity (severe and non-severe). Three monocyte subsets (classical, CL; intermediate, INT; non-classical, NC) were analyzed with flow cytometry upon the patients' hospital admission. A total of 42 patients with COVID-19 and 30 controls participated in this study. The patients' conditions were either severe (n = 23) or non-severe (n = 19). All patients' monocyte and HLA-DR expressions were decreased compared with the controls (p < 0.05). Per disease severity, all monocyte subsets were not significant with disease severity; however, the HLA-DR expressions of CL monocytes (p = 0.002) and INT monocytes (p = 0.025) were more decreased in the severe patient group. In patients with various clinical features, NC monocytes were more affected. Based on these results, NC monocytes were more decreased in acute COVID-19 cases, though related various clinics decreased all monocyte subsets in these patients. Decreased monocyte HLA expressions may be a sign of immune suppression in severe patients, even when the percentage of monocyte levels has not decreased yet. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of T- and B-regulatory cells (Tregs and Bregs) in the pathogenesis of idiopathic granulomatous mastitis (IGM). This study includes 47 patients with pathologically proven IGM (Group P) and 26 healthy subjects (Group C). The patients in Group P were divided into two groups according to whether their lesions were active (Group PA, n: 21) or in remission (Group PR, n: 26). By using flow-cytometry, the frequencies of CD3+CD4+CD45RA−Foxp3high activated Tregs (aTregs), CD3+CD4+CD45RA−Foxp3low non-suppressive Tregs, CD3+CD4+CD45RA+Foxp3low resting Tregs (rTregs), CD3+CD4+CD25+Foxp3− T-effector cells (Teff), total Tregs and Bregs were analyzed in all subjects. The frequency of the Teff cells was statistically higher in Group P when compared with Group C (p =.004). The Foxp3 expression of Treg cells and the frequency of non-suppressive Tregs in Group P were statistically lower than Group C (p =.032 and p =.02, respectively). In addition, Group PR's Foxp3 expressions were statistically lower than Group C (p =.027); Group PR's aTregs ratio was statistically lower than Group PA (p =.021); and the non-suppressive Tregs ratio of Group PR was lower than both Group PA and Group C (p =.006 and p <.0001). No significant differences were seen Bregs and B cell subsets. Significant changes in Foxp3 expression and Treg subsets were seen in patients with active IGM lesion and in remission. This study shows an intrinsic defect of Tregs in patients with IGM. [ABSTRACT FROM AUTHOR]

Background: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods: We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p <.001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score (p =.020, p =.003, p =.014, p =.013, p =.020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p =.012, p =.022, p =.011; respectively). Conclusion: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID‐19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid‐derived suppressor cells (MDSCs) in COVID‐19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID‐19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings—aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C‐reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty‐one patients with COVID‐19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets—polymorphonuclear MDSCs (PMN‐MDSCs) and monocytic MDSCs—by flow cytometric immunophenotyping, and PMN‐MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID‐19. Total MDSCs, PMN‐MDSCs, mature PMN‐MDSCs and monocytic MDSCs were significantly higher in patients with COVID‐19 compared with the healthy controls (P <.05). Only PMN‐MDSCs and their immature PMN‐MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C‐reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID‐19. These findings suggest that MDSCs play a role in the pathogenesis of COVID‐19, while PMN‐MDSCs, especially immature PMN‐MDSCs, are associated with the severity of the disease. [ABSTRACT FROM AUTHOR]

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency. [ABSTRACT FROM AUTHOR]

• Inborn errors of immunity (IEI) constitute a heterogeneous group of mainly monogenic primary immune disorders. • The human gene connectome analysis shows that around 3110 genes may be potentially included among IEI-causing genes. • The correct molecular diagnosis is crucial for the classification and subsequent therapeutic management of patients with IEI. • NGS has facilitated genetic examinations of inherited disorders, thus allowing a suitable molecular diagnosis in individuals with IEIs. Patients with inborn errors of immunity (IEI) present with a heterogeneous clinical and immunological phenotype, therefore a correct molecular diagnosis is crucial for the classification and subsequent therapeutic management. On the other hand, IEI are a group of rare congenital diseases with highly diverse features and, in most cases, an as yet unknown genetic etiology. Next generation sequencing has facilitated genetic examinations of rare inherited disorders during the recent years, thus allowing a suitable molecular diagnosis in the IEI patients. This review aimed to investigate the current findings about these techniques in the field of IEI, suggesting an efficient stepwise approach to molecular diagnosis of inborn errors of immunity. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2+ BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2+ BCSCs (CD44+CD24−HER2+), HER2− BCSCs (CD44+CD24−HER2−), HER2− primary culture cells (CD44+CD24+HER2−) and triple positive primary culture cells (CD44+CD24+HER2+). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2+ BCSCs than in primary culture. HER2− BCSCs were more resistant to drugs than HER2+ BCSCs. Our findings suggest that the presence of HER2− BCSCs may be responsible for primary trastuzumab resistance in HER2+ BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that, compared with body mass index (BMI) alone, central obesity would provide added information regarding types of asthma (allergic, nonallergic) and asthma severity. Materials and Methods: A total of 150 children aged between 7-17 years with 50 allergic asthma, 50 nonallergic asthma and 50 controls were included in the study. Height, weight, waist and hip circumferences of the groups were measured. Waist-to-hip ratio and BMI were calculated. Pulmonary function test results were recorded. The relation between anthropometric measurements, asthma, atopy, obesity and each other was analyzed. Results: Obesity according to BMI was higher in the group with allergic asthma than nonallergic asthma and the control group (p: 0.014). A positive correlation was found between asthma and BMI percentile, BMI z score and waist-to-hip ratio (p: 0.002; 0.003; 0.040, respectively). Children with obesity according to waist circumference were more frequent in the groups with allergic and nonallergic asthma compared to the control group (p: 0.048). There was a significant relationship between asthma severity and central obesity (p: 0.048). FEV1 / FVC and FEF25-75 were lower in the asthmatic groups compared to the control group (p: 0.028; 0.012, respectively). Conclusion: This study showed that central obesity was associated with asthma and asthma severity, but not with atopy. More investigation is needed to clarify how central obesity in children affects the control of asthma and the response to asthma medication. [ABSTRACT FROM AUTHOR]

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper‐IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8‐deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. Methods: Peripheral blood ILC1‐3 subsets of 16 DOCK8‐deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post‐transplant DOCK8‐deficient patients (n = 12) by flow cytometry and real‐time qPCR. Sorted total ILCs from DOCK8‐ or STAT3‐mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL‐7, IL‐23, and IL‐12 by cell culture, flow cytometry, and phospho‐flow assays. Results: DOCK8‐deficient but not STAT3‐mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8‐deficient ILC1‐3 subsets had defective proliferation, expressed lower levels of IL‐7R, responded less to IL‐7, IL‐12, or IL‐23 cytokines, and were more prone to apoptosis compared with those of healthy controls. Conclusion: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8‐deficient patients to infections. [ABSTRACT FROM AUTHOR]

Aim: This study was planned to research the relationship between doxorubicin cardiomyopathy and the soluble Fas (sFas) level. Materials and Methods: Two groups of rats were included in the study. The control group was given physiological saline, while the study group was given doxorubicin. The rats, whose blood samples were taken weekly, were sacrificed and their myocardial tissues were removed. The tissues were examined in terms of morphological changes and surface Fas expression, while the blood samples were examined in terms of sFas level. Results: In the study group, the sFas levels at 2nd-9th weeks were higher than those found at 1st week before administrating the drug, and the increase at 2nd-7th weeks was meaningful. In addition, sFas levels were gradually increased each week during 1st-5th weeks when compared to the values of a previous week, and the increase during the first 4 weeks was meaningful. After the 5th week, the values gradually decreased each week. The mean values of the study group at 1st-8th weeks were higher than those of the control group, and the increases at 2nd-8th weeks were meaningful. The severe forms of interfibrillar hemorrhage, vascular dilatation, myocardial necrosis, inflammatory infiltration, and splitting of muscle fibers occurred with 15, 15, 17.5, 20, and 22.5 mg/kg dose of medicine, respectively. Conclusions: As the tissue injury increased, the increasing cell-surface Fas expression and sFas plasma level at the acute phase of doxorubicin-related cardiotoxicity decreased. The sFas level determined at acute phase may be helpful in predicting the existing injuries and possible late-term problems. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to determine the effects of zinc and melatonin supplements on the immunity parameters of female rats with breast cancer induced by DMBA. Methods: Group 1; Control, Group 2; 7,12-dimethylbenz[a]anthracene (DMBA), Group 3; DMBA + zinc, Group 4; DMBA + melatonin, Group 5; DMBA + zinc + melatonin. The rats’ breast cancer was induced by DMBA 80 mg/kg. Groups 3-5 received daily 5 mg/kg doses of zinc, melatonin, and zinc + melatonin, respectively. Lymphocyte rates, T-lymphocyte subgroups, B-lymphocyte and natural killer cells (NK), and natural killer T (NKT) were evaluated. Results: The most significant increase in lymphocyte, T-lymphocyte, and CD4 lymphocyte rates was found in Group 5. The highest NKT cell rates were found in Group 3. Conclusions: Findings show that zinc and melatonin supplements have led to an increase in the immunity parameters of rats with breast cancer. [ABSTRACT FROM AUTHOR]

Children with Down syndrome (DS) have a high incidence of recurrent respiratory tract infections, leukaemia and autoimmune disorders, suggesting immune dysfunction. The present study evaluated the role of the CD19 complex and memory B cells in the pathogenesis of immunodeficiency in children with DS. The expression levels (median fluorescein intensity—MFI) of CD19, CD21 and CD81 molecules on the surface of B cells and memory B cell subsets were studied in 37 patients and 39 healthy controls. Twenty-nine of the DS group had congenital cardiac disease. The B cell count was significantly low in children with DS compared with healthy age-matched controls for all three age groups (under 2 years; 2–6 years and older than 6 years). The MFI of CD19 was reduced in all the age groups, whereas that of CD21 was increased in those older than 2 years with DS. The expression level of CD81 was significantly increased in those older than 6 years. Age-related changes were also detected in memory B cell subsets. The frequency of CD27+IgD+IgM+ natural effector B cells was reduced in children with DS who had needed hospitalisation admission due to infections. The observed intrinsic defects in B cells may be responsible for the increased susceptibility of children with DS to severe respiratory tract infections. [ABSTRACT FROM AUTHOR]

Background and Aims The appropriate treatment of pandemic H1N1 influenza which was first identified in April 2009 in Mexico is insufficient especially for immunocompromised patients. We aimed to evaluate the features and prognostic factors of the children with H1N1, especially immunocompromised ones, and whether intravenous immunoglobulin G ( IVIG) replacement could aid for a better outcome. Methods Twenty-one hospitalized children with laboratory-confirmed H1N1 were evaluated retrospectively. Data were extracted from files and electronic medical records. Results The median age was 37 (1-216) months; 62% of them were under 5 years of age and 71.4% had one or more underlying disorders. Main symptoms were high fever, cough, fatigue and vomiting. Lower respiratory tract manifestations were seen in 66.6% of children. Mortality rate was 4.7%. The patient who died had the lowest lymphocyte (100/mm3), thrombocyte (21 000/mm3) and highest blood urea nitrogen (87 mg/d L) levels. Fifty-eight percent of evaluated patients had one of the primary immunodeficiency disorders. Surprisingly, none of the six patients with primary immunodeficiency who are on regular IVIG replacement needed intensive care unit and died. Although median durations of cough, fever and hospitalization were lower, they did not change statistically according to get IVIG replacement regularly ( P = 0.47, 0.97, 0.09, respectively). Conclusion Our study is important while it is the first one that shows the course of primary immunodeficient children with H1N1 infection who were on regular IVIG replacement. A trial of high-dose IVIG may be a useful adjunctive therapy in severe H1N1 influenza, particularly in the immunocompromised patients. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, high incidence of cancer, and increased sensitivity to ionizing radiation. The authors report a case of dysgerminoma in a child with high α-fetoprotein, CA125 and β-human chorionic gonadotropin, who has been followed-up for ataxia-telangiectasia for 2 years. [ABSTRACT FROM AUTHOR]