Immune response variation in mild and severe COVID-19 patients.

Sixty patients with COVID-19 infection were categorized into mild and severe groups, and their immune response was analyzed using flow cytometry and complete blood count. An observed increase in immune activation parameters, notably a higher percentage of CD4 lymphocytes co-expressing CD69 and CD25 molecules, and enhanced activity of the macrophage-monocyte cell line was noted in the mild group. Although Group 2 (severe COVID) had fewer CD4 cells, significant migration and proliferation were evident, with increased CD4CD69, CD8 HLA-DR+, and CD8CD69 lymphocytes. The CD4 to CD8 ratio in Group 1 suggested potential autoimmune reactions, while Group 2 indicated potential immunosuppression from severe infection and employing immunosuppressive drugs. Additionally, Group 2 exhibited an increased neutrophil count, hinting at possible bacterial co-infection. Group 1 showed differences in CD4RO and CD8RA lymphocyte populations, implying that cellular immunity plays a role in developing efficient postinfectious immunity. This intimation suggests that vaccination might mitigate the severity of the coronavirus infection and prevent complications, including long-term COVID-19.

Efficacy and Safety of Statin Treatment in Children with Familial Hypercholesterolemia: Outcomes of 20 Years of Experience.

BACKGROUND: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. METHODS AND RESULTS: The study included 84 children aged 1-18 years with FH. For the whole study group, 535 medical visits were recorded. The mean follow-up period was 33.6 months. Molecular testing performed in 55 children (65%) provided genetic confirmation of the diagnosis in 36 children (43%). Twenty-seven children (32%) were treated pharmacologically with statins. Follow-up during the treatment averaged 29 months. Treatment with statins was associated with a mean reduction in total cholesterol and LDL-cholesterol levels of 24 and 33% from the baseline. Symptoms of statin intolerance occurred incidentally and did not require amendment in the treatment protocol. Significantly higher values of body weight, height, and BMI were found only among girls older than 10 years who were treated with statins. CONCLUSIONS: These data confirm a high efficacy and a good safety profile of statin treatment in children with FH, demonstrating no harm to physical development. However, there is a need for further cause-and-effect research regarding associations between long-term treatment with low-cholesterol, low-fat diets, statin therapy, and excessive weight gain.

Professional activity, gender and disease-related emotions: The impact on parents' experiences in caring for children with phenylketonuria.

Introduction: Clinical management of rare diseases often fails to acknowledge the challenges faced by caregivers. Whilst management of phenylketonuria (PKU) may not be considered as dire as other conditions, most studies primarily concentrate on clinical issues, dietary adherence, or the quality of life of the PKU patients, leaving caregivers in the background. The aim of the study was to evaluate the psychosocial effects of PKU on family caregivers. Methods: Between October 30th, 2022 and February 28th, 2023, we collected data from caregivers of children with PKU using an anonymous, self-administered, computer-assisted online questionnaire. The survey was distributed among to patients during their regular visits to five Polish PKU treatment centers. Results: A total of 159 Polish caregivers of children with PKU completed the survey. This research shows that while women caregivers were more likely to be unemployed due to their responsibilities for childcare (50.3% compared to 0% for men), and men caregivers were more likely to be employed full-time (93.8% compared to 40.6% for women), the former reported higher emotional engagement in caregiving (88.1% vs 56.3% respectively). Significantly, unemployed mothers reported higher levels of loneliness, helplessness, and emotional control problems, and lacked psychological/emotional support more often than employed mothers. This research also shows a statistically significant positive correlation between mothers' education level and financial situation (p < 0.05) and education level and professional activity (p < 0.01). Additionally, a significant positive correlation was found between perceived financial situation and feeling of happiness (p < 0.001), and between financial situation and professional activity (p < 0.001). Finally, a significant positive correlation was observed between feeling of happiness and professional activity (p < 0.05). Conclusions: According to our findings, there is a link between subjective happiness, financial situation, and professional activity among female caregivers. The relationship between these factors goes beyond just the income earned from work. The results of our study imply that there could even be a therapeutic advantage for working mothers. It is crucial to recognize the emotional difficulties that employed mothers may experience while taking care of a child with PKU, and to provide them with the necessary assistance and resources to meet their needs. Additionally, our results may provide a foundation for redefining the support system for caregivers in Poland.

Lack of relationship between 25-hydoxyvitamin D concentration and a titer of antibodies to hepatitis B surface antigen in children under 12 years of age.

The effect of vitamin D levels on the response to the hepatitis B vaccine in childhood and the induced levels of antibodies against the hepatitis B surface antigen (anti-HBs) is not yet well understood. The study aimed to investigate the relationship between age, serum 25-hydroxyvitamin D (25(OH)D) concentration and anti-HBs titer among children under 12 years old. Serum 25(OH)D concentration and anti-HBs titer were determined in 352 healthy Caucasian children with the average age of 4.2 (2.5; 6.3) years. All children were vaccinated with 3 doses of hepatitis B vaccine (Engerix-B, GlaxoSmithKline Pharmaceuticals Limited) in infancy according to the Centers for Disease Control and Prevention recommendations. Only 14.5% of children had an optimal concentration of 25(OH)D ≥ 30 ng/mL and 71.9% children had a seroprotective anti-HBs titer ≥ 10 mIU/mL. Significant negative correlations were found between 25(OH)D, anti-HBs titer and age (r = -0.420, p = 0.000; r = -0.425, p = 0.000, respectively), and a weak positive correlation between 25(OH)D concentration and anti-HBs titer (r = 0.243, p = 0.000). Analysis of six clusters of children demonstrated that age is the main factor affecting anti-HBs titer. One third of children under 12 years of age had nonprotective anti-HBs titer < 10 mIU/mL and around 40% had vitamin D deficiency. We conclude that vitamin D status has no impact on anti-HBs titer in children vaccinated against hepatitis B virus in infancy. Age, so time since the receipt of the last dose of hepatitis B vaccine, is the main factor influencing a decline in anti-HBs titer.

BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw.

Objective: We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains. Material: We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies. Results: Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) (p = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed (p = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study (p = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis. Conclusion: The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably via their production of IFN-γ.

Innate and Acquired Cellular Immunity in Children with Familial Hypercholesterolemia Treated with Simvastatin.

The aim of this cross-sectional study was to assess the influence of simvastatin treatment in children with familial hypercholesterolemia (FH) on parameters of cellular immunity. Twenty-six children with FH were included, of which thirteen were treated with 10 mg simvastatin for at least 26 weeks, and thirteen were age- and sex-matched with a low-cholesterol diet only. Total WBC count and lipid profile were measured. Flow cytometry was used to identify lymphocyte subsets and determine the expression of adhesion molecules (AM) and toll-like receptors (TLRs) on leukocytes. No differences were found in the basic values of peripheral blood count and subpopulations of lymphocytes between groups. The percentage of granulocytes with the expression of AM was higher in those treated with statins. The TLR-2 expression on granulocytes and monocytes showed higher values, whereas the TLR-4 expression was lower on lymphocytes and granulocytes in simvastatin-treated children. Treatment with simvastatin in children with FH is not associated with alterations in the amounts of granulocytes and monocytes. There is no association between statin treatment and the pattern of peripheral blood lymphocyte subpopulations. The role of AM and TLRs needs further investigation, given the effect of statins on the innate immunity may be important for their efficacy and safety during growth.

Phenylketonuria Patients' and Their Caregivers' Perception of the Pandemic Lockdown: The Results of a National Online Survey.

The first pandemic lockdown dramatically impacted many aspects of everyday life, including healthcare systems. The purpose of this study was to identify problems of patients with phenylketonuria (PKU) and their parents/caregivers during that time. We aimed to analyse potential differences in the self-reported compliance and characteristics of contacts with a doctor/dietitian before and during the pandemic lockdown and the perception of access to special food and opinions on remote contacts between a particular group of respondents. All participants (n = 614) were asked to complete an online questionnaire that consisted of 31 questions on pandemic-related events and circumstances which may have directly or indirectly impacted health and treatment. The people who completed the survey were divided into three groups: parents of PKU children (n = 403), parents of PKU adults (n = 58) and PKU patients older than 16 years (n = 153). The differences among the three analysed groups were found in the number of contacts, the way of contacting a doctor/dietitian during the pandemic and satisfaction with remote contact. Caregivers of children with PKU reported better therapy compliance, more frequent contacts with specialists and more satisfaction with remote visits than adult patients. We also observed a relationship between satisfaction from remote contact and self-reported frequency of contacts with a doctor/dietitian, as well as a relationship between satisfaction from remote contact and recommended blood Phe levels reported by both patients and caregivers. Travel time exceeding three hours from the respondents' location to their doctor was associated with higher odds of their recognition of remote contact as a method of PKU treatment only in the group of caregivers. In the caregiver groups, the reported worse access to low-Phe products during the lockdown was linked to the perceived difficulty of maintaining the diet. However, such a relationship was not found among patients. In conclusion, significant differences in the perception of the pandemic lockdown and its impact on health and treatment-related issues were found.

Effect of Statin Therapy on the Plasma Concentrations of Retinol, Alpha-Tocopherol and Coenzyme Q10 in Children with Familial Hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) requires early treatment. However, statins, which are regarded the first-line therapy, have an influence on redox balance. Antioxidant vitamins are important for many metabolic processes in the developing body. There are few data available on the long-term safety of statin use in children. The aim of this study was to evaluate the influence of statin treatment in children with FH on plasma concentrations of antioxidant vitamins: retinol, alpha-tocopherol and coenzyme Q10. METHODS: The first study group consisted of 13 children aged 10-18 years treated with simvastatin for at least 6 months, and the second group comprised 13 age- and sex-matched children with hypercholesterolemia, in whom pharmacological treatment had not been applied yet. Analyses were performed using a high-performance liquid chromatograph coupled with a MS detector. RESULTS: The analysis did not reveal significant differences in the concentration of retinol, alpha-tocopherol or coenzyme Q10 between the studied groups. The adjustment of the concentrations of the vitamins to the cholesterol level also indicated no significant differences. We found no deficits in antioxidant vitamins in patients treated with statins, or any risk of adverse effects associated with an increase in their concentration. CONCLUSION: There is no rationale for additional supplementation using antioxidant vitamins or modification of low-fat and low-cholesterol diet in pediatric patients treated with statins.

Helicobacter pylori Infection in Children with Phenylketonuria Does Not Depend on Metabolic Control and Is Not More Frequent Than in Healthy Subjects-A Cross-Sectional Study.

In a small preliminary study, phenylketonuria and poor metabolic control were suggested as risk factors for Helicobacter pylori infection in children as detected with an antigen stool test. We aimed to determine Helicobacter pylori prevalence in an adequately sized group of individuals with phenylketonuria and healthy subjects using the standard gold test (urea breath test). Further, we correlated Helicobacter pylori infection with metabolic control. The study comprised 103 individuals with phenylketonuria and 103 healthy subjects on whom a 13C urea breath test was performed. Blood phenylalanine levels in the preceding year were analysed. The infection rate did not differ between individuals with phenylketonuria and healthy subjects (10.7% vs 15.5%; p = 0.41). The frequency of testing and phenylalanine concentrations of Helicobacter pylori-positive and Helicobacter pylori-negative patients with phenylketonuria did not differ (p = 0.92 and p = 0.54, respectively). No associations were detected for body mass index or metabolic control. Forward stepwise regression models revealed that age (p = 0.0009-0.0016) was the only independent correlate of Helicobacter pylori infection with a relatively low fraction of the variability of the condition being explained (adjR2 = 0.0721-0.0754; model p = 0.020-0.023). In conclusion, Helicobacter pylori infection in phenylketonuria is not more frequent than in the general population. Moreover, it does not depend on metabolic control.

The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria.

The present study assessed patients' metabolic control of phenylketonuria (PKU) during the first 2020 COVID-19 lockdown in Poland. Blood (phenylalanine) Phe results of the tests of 535 patients, performed in 2019 and in the first months of 2020, were analysed. The six-week lockdown period was compared to the preceding six-week period as well as to the two corresponding periods of 2019 (three non-lockdown periods). More patients failed to perform Phe tests in the lockdown period (32.7%) than in non-lockdown periods (15.6%, 15.1%, 17.2%; p < 0.001 for all). The median Phe levels for those patients who performed testing in all the four periods did not differ between periods. However, these patients tended to perform only one test during the lockdown (ORs: 1.43 to 1.60; 95% CI: from 1.01-2.04 to 1.11-2.30, p-value 0.02 to 0.005). Patients who did not take blood during the lockdown (46.7%) performed significantly fewer blood tests in the remaining periods (median : 1 <0-1> vs. 2 <1-4>; p < 0.001). In conclusion, direct assessment of patients' compliance based upon Phe levels during the pandemic lockdown was not possible. Pre-pandemic non-compliant patients frequently failed to perform the test during the lockdown, whereas the previously compliant ones were more likely to perform only one test. This strongly suggests that metabolic control might have worsened.

The Impact of the COVID-19 Pandemic on the Perception of Health and Treatment-Related Issues among Patients with Phenylketonuria in Poland-The Results of a National Online Survey.

There is agreement that the pandemic has affected the healthcare system and behaviour of patients. This study aims to identify problems encountered by patients with phenylketonuria (PKU) and their parents/caregivers during the six-week pandemic lockdown in Poland (15 March to 30 April 2020). To determine the factors that influenced health and treatment-related issues, as well as the respondents' perception of the impact of the pandemic, study participants were asked to complete a non-validated online questionnaire comprising 31 questions (including 27 single-choice, two multiple-choice and two open-ended ones). A total of 571 patients or their parents completed the questionnaire, with 9.5% of respondents not performing any blood phenylalanine (Phe) test in the analysed period, 21.3% declaring a blood Phe increase, and 15.3% a decrease. Increased problems in contacting the doctor or dietitian were reported by 26.1% of subjects, whereas 39.3% of them felt restricted access to dietary products. Most (63.4%) participants were satisfied with remote contact with their PKU clinic. Better compliance was associated with higher odds of acceptance of remote contact and of reporting fewer problems with contacting the doctor, and with lower odds of missing Phe testing. Self-reported high stress was associated with higher odds of reporting the limited availability of low-Phe products and Phe-free formulas, as well as with increased Phe concentrations and non-PKU-related health problems. These patients also had poor dietary compliance and experienced more problems in contacting specialists. Health and treatment-related problems experienced during the pandemic lockdown were related to a higher intensity of stress in patient's family and worse therapy compliance before the pandemic. Previous experience of remote visits resulted in a better perception of this method of contact. It seems that this form of communication should be popularized and improved to increase therapy effectiveness in case of different limitations in the future. Special attention should be paid to vulnerable patients who may be at extra risk when the provision of standard care is affected.

Endothelin-1 Serum Concentration in Pediatric Chronic Idiopathic Uveitis.

PURPOSE: The aim of our study was to determine endothelin-1 (ET-1) concentration in chronic idiopathic uveitis in children and adolescents depending on anatomical location and grade of inflammation. METHODS: The cross-sectional study was conducted among 17 patients with chronic idiopathic uveitis and 22 healthy controls. Concentration of ET-1 in serum was determined using a commercially available ELISA kit. The concentration of C reactive protein (CRP) in serum was determined by immunoturbidimetric method using CRP4 reagent kit (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: Statistically significant difference between ET-1 concentration in patients with chronic idiopathic uveitis and controls was found 1.33 (1.22; 1.48) vs 1.93 (1.1; 3.11), p = 0.008). No correlations were found between ET-1 concentration and age, either in chronic idiopathic uveitis patients or controls. Nine out of 17 patients presented with anterior uveitis, 5 with posterior and 3 with panuveitis. There were no differences in ET-1 concentration between anterior, posterior and panuveitis (p = 0.634), and in terms of grade of inflammation. CONCLUSION: ET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.

Interstitial Lung Disease in Children With Selected Primary Immunodeficiency Disorders-A Multicenter Observational Study.

Primary immunodeficiencies (PIDs) are rare disorders of the immune system encompassing inborn errors of immunity. Primary antibody deficiencies constitute the largest group of PID with common variable immunodeficiency (CVID) being the most common symptomatic form. Combined immunodeficiencies (CID) accompanied by antibody deficiency can mimic CVID and these patients need the verification of the final diagnosis. Respiratory involvement, especially interstitial lung disease (ILD), poses a relevant cause of morbidity and mortality among patients with PID and in some cases is the first manifestation of immunodeficiency. In this study we present a retrospective analysis of a group of children with primary immunodeficiency and ILD - the clinical, radiological, histological characteristics, treatment strategies and outcomes. Eleven children with PID-related ILD were described. The majority of them presented CVID, in three patients CID was recognized. All patients underwent detailed pulmonary diagnostics. In eight of them histological analysis of lung biopsy was performed. We noted that in two out of 11 patients acute onset of ILD with respiratory failure was the first manifestation of the disease and preceded PID diagnosis. The most common histopathological diagnosis was GLILD. Among the analyzed patients three did not require any immunosuppressive therapy. All eight treated children received corticosteroids as initial treatment, but in some of them second-line therapy was introduced. The relevant side effects in some patients were observed. The study demonstrated that the response to corticosteroids is usually prompt. However, the resolution of pulmonary changes may be incomplete and second-line treatment may be necessary.

The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries.

Background: Variants in recombination-activating genes (RAG) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries. Methods: Demographic, clinical, and laboratory data were collected from RAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay. Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID (n = 20), OS (n = 37), and LS/CID (n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% (n = 47) of patients with RAG1 variants carried p.K86Vfs*33 (c.256_257delAA) allele, either in homozygous (n = 18, 27%) or in compound heterozygous (n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs*33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs*33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. Conclusion: We propose that RAG1 p.K86Vfs*33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival.

Systemic Redox Imbalance in Patients with Chronic Granulomatous Disease.

The aim of our study was to evaluate redox status, enzymatic and non-enzymatic antioxidant barriers, oxidative damage of proteins, lipids and DNA, as well as concentration of coenzyme Q10 and vitamins A and E in patients with chronic granulomatous disease (CGD). The study was performed on fifteen Caucasian individuals (median age 24 years and seven months) diagnosed with CGD. The mutation in the NCF1 gene was confirmed in ten patients, and in the CYBB gene in five patients. We demonstrated high levels of total oxidant status (TOS) and oxidative stress index (OSI), lipids (↑8-isoprostanes (8-isoP), ↑4-hydroxynonenal (4-HNE)), proteins (↑advanced oxidation protein products (AOPP)) and DNA (↑8-hydroxy-2'-deoxyguanosine (8-OHdG)) oxidation products in CGD individuals as compared to sex- and age-matched healthy controls. We showed enhanced serum enzymatic activity of catalase (CAT) and superoxide dismutase-1 (SOD) and significantly decreased coenzyme Q10 concentration. Our study confirmed redox disturbances and increased oxidative damage in CGD patients, and indicated the need to compare redox imbalance depending on the type of mutation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The question regarding effectiveness of antioxidant therapy in patients with CGD is open, and the need to establish guidelines in this area remains to be addressed.

Endothelin-1 Serum Concentration is Lower in Children and Adolescents with High Myopia, a Preliminary Study.

The aim of this study is to evaluate the levels of enothelin-1 (ET-1) in children and adolescents with high myopia and its association with the axial length of the eye and the presence of myopic retinal degeneration. The cross-sectional study was carried out in 57 patients with high myopia and 29 control subjects. Serum concentrations of ET-1 were measured using enzyme-linked immunosorbent assay (ELISA) kit. A significantly lower concentration of ET-1 in highly myopic patients compared to controls was found (1.47 (0.91; 1.87) vs. 1.94 (1.1; 2.69) pg/mL, p = 0.005). In patients with high myopia, a weak negative correlation between ET-1 concentration and the longest axial length out of the two eyes was found (r = -0.255, p = 0.0558). Further analysis revealed statistically significant differences in ET-1 concentration between patients with the axial length of the eye > 26 and ≤ 26 mm (p < 0.041) and patients with the axial length of the eye > 26 mm and controls (p < 0.001). ET-1 expression is disturbed in highly myopic children and adolescents. Lower ET-1 concentration in patients with the axial length of the eye > 26 mm may co-occur with high myopia and should be considered a risk factor in the pathophysiology of high myopia progression.

BCG Moreau Vaccine Safety Profile and NK Cells-Double Protection Against Disseminated BCG Infection in Retrospective Study of BCG Vaccination in 52 Polish Children with Severe Combined Immunodeficiency.

OBJECTIVES: The aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients. MATERIAL: The profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children's Memorial Health Institute, Warsaw (CMHI), in the years 1980-2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134-1141). RESULTS: Significantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study-119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with T-B+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided. CONCLUSION: The BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients' survival and the fact that they protect against BCG infection.

Antioxidant Defense, Redox Homeostasis, and Oxidative Damage in Children With Ataxia Telangiectasia and Nijmegen Breakage Syndrome.

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated in vitro and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the in vivo phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Twenty two Caucasian children with AT and twelve patients with NBS were studied. Enzymatic and non-enzymatic antioxidants - glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase-1 (SOD) and uric acid (UA); redox status-total antioxidant capacity (TAC) and ferric reducing ability of plasma (FRAP); and oxidative damage products-8-hydroxy-2'-deoxyguanosine (8-OHdG), advanced glycation end products (AGE), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE) protein adducts, and 8-isoprostanes (8-isop) were evaluated in serum or plasma samples. We showed that CAT, SOD and UA were significantly increased, while TAC and FRAP levels were statistically lower in the plasma of AT patients compared to controls. In NBS patients, only CAT activity was significantly elevated, while TAC was significantly decreased as compared to healthy children. We also showed higher oxidative damage to DNA (↑8-OHdG), proteins (↑AGE, ↑AOPP), and lipids (↑4-HNE, ↑8-isop) in both AT and NBS patients. Interestingly, we did not demonstrate any significant differences in the antioxidant defense and oxidative damage between AT and NBS patients. However, in AT children, we showed a positive correlation between 8-OHdG and the α-fetoprotein level as well as a negative correlation between 8-OHdG and IgA. In NBS, AGE was positively correlated with IgM and negatively with the IgG level. Summarizing, we demonstrated an imbalance in cellular redox homeostasis and higher oxidative damage in AT and NBS patients. Despite an increase in the activity/concentration of some antioxidants, the total antioxidant capacity is overwhelmed in children with AT and NBS and predisposes them to more considerable oxidative damage. Oxidative stress may play a major role in AT and NBS phenotype.

Whey Protein Concentrate WPC-80 Improves Antioxidant Defense Systems in the Salivary Glands of 14-Month Wistar Rats.

Whey protein concentrate (WPC) is characterized by powerful antioxidant properties, but its effect on redox homeostasis of salivary glands of aging organisms is still unknown. In this study, we are the first to evaluate the antioxidant barrier of salivary glands of 14-month Wistar rats fed WPC-80. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) as well as concentrations of reduced glutathione (GSH) are estimated in the submandibular and parotid glands of rats administered WPC-80 intragastrically for a period of 7 and 14 days. We demonstrate a significant increase in GSH, GPx and SOD in the salivary glands of rats fed WPC-80 for 14 days and a significant increase in TAS, GPx and SOD in the parotid glands of rats fed WPC-80 for 7 days compared to control rats. The beneficial effects of WPC-80 on salivary glands are also demonstrated by lower TOS and OSI in the parotid glands of rats fed WPC-80 compared to the submandibular glands. In summary, we demonstrate that WPC-80 improves redox homeostasis in salivary glands, particularly in the parotid glands of old rats.

Vitamin D deficiency in children with recurrent respiratory infections, with or without immunoglobulin deficiency.

PURPOSE: The objective of this study was to evaluate thevitamin D concentration in patients with recurrent respiratory infections with or without immunoglobulin G, A or M (IgG, IgA, IgM) deficiency, and to find a correlation between the vitamin D concentration and the response to hepatitis B vaccination. MATERIALS AND METHOD: The study involved 730 patients with recurrent respiratory infections. The concentration of 25-hydroxyvitamin D (25(OH)D), immunoglobulins G, A and M, anti-HBs was determined. RESULTS: The tests showed that 11% of patients presented IgG levels below the age related reference values. Children with reduced IgG concentration were also found to have significantly lower vitamin D concentrations in comparison to children with normal IgG. Vitamin D deficiency was observed in schoolchildren between 7 and 18 years of age. No correlation was found between 25(OH)D concentration and Hbs antibody levels. CONCLUSIONS: An investigation of a large group of patients who have recurrent infection found patients with IgG deficiency to whom special proceeding have to be performed: 1. Significantly lower vitamin D concentration observed in the group of children with IgG deficiency implicated in long-lasting monitoring of vitamin D level require adding to the practice guidelines for Central Europe 2013. 2. Intervention treatment with suitable doses of vitamin D to clarified metabolism of vitamin D has to be plan for children with IgG deficiency and significant lower vitamin D concentration.