Assessment of autoantibodies in paediatric population with primary immunodeficiencies: a pilot study.

BACKGROUND: The correlation between primary immunodeficiencies (PIDs) and autoimmunity shows ethnic and geographical diversity. The aim of our study was to accumulate more data in paediatric PID population. METHODS: 58 children aged 1-17 and with PID (study group) and 14 age-matched immunocompetent individuals (control group) were included in the study. Serum levels of 17 different specific IgG antibodies against autoantigens were measured by means of a quantitative enzyme immunoassay. Immunoglobulin levels were analysed in relation to a detailed medical examination. RESULTS: Autoantibodies against one or more antigens were detected in the sera of 24.14% (n = 14) subjects in the study group. The most frequent were anti-thyroid peroxidase (anti-TPO) antibodies (n = 8; 13.8%). Anti-TPO antibody levels were elevated more often in PID patients with a positive family history of autoimmune diseases (p = 0.04). The screening for anti-deamidated gliadin peptide (DGP) and anti-tissue transglutaminase (tTG) antibodies in our series allowed identifying two previously undiagnosed cases of coeliac disease in PID patients. There was no statistically significant difference between the study and the control group in terms of the autoantibodies prevalence. CONCLUSIONS: This study provides data on the prevalence of autoantibodies in paediatric population diagnosed with PID. Selected autoantibodies (i.e. anti-tTG, anti-DGP) might be useful for the screening of PID to avoid the delay of diagnosis of an autoimmune disease.

Before and After: Attitude and Adverse Effects Induced by the First and Second Doses of mRNA BNT162b2 Vaccine among Healthcare Professionals in the First Weeks after Their Introduction in Poland.

BACKGROUND: In the last days of December 2020, the SARS-CoV-2 virus vaccine BNT162b2 (Comirnaty, Pfizer-BioNTech) was introduced, for the first time, for wide use in Poland. According to the vaccination schedule, healthcare workers were the first to receive the vaccine. The aim of this study was to analyse the attitudes of those who were determined to be vaccinated, with particular reference to their concerns, attitudes towards vaccination advocacy and sources of knowledge on vaccination, as well as the incidence of adverse reactions. METHODS: The study had a three-stage design. Respondents completed a self-administered questionnaire before receiving the 1st and 2nd vaccine doses and 2 weeks after receiving the 2nd dose. A total of 2247 responses were obtained (1340 responses in the first stage, 769 in the second and 138 in the third). RESULTS: The main source of knowledge on vaccination was the Internet (32%; n = 428). Of the respondents, 6% (n = 86) reported anxiety before the 1st dose of the vaccine, which increased to 20% (n = 157) before the 2nd dose. A declaration of willingness to promote vaccination among their families was made by 87% (n = 1165). Among adverse reactions after the 1st dose of the vaccine, respondents most frequently observed pain at the injection site (n = 584; 71%), fatigue (n = 126; 16%) and malaise (n = 86; 11%). The mean duration of symptoms was 2.38 days (SD 1.88). After the 2nd dose of vaccine, similar adverse reactions-pain at the injection site (n = 103; 75%), fatigue (n = 28; 20%), malaise (n = 22; 16%)-predominated among respondents. Those who declared having had a SARS-CoV-2 virus infection (p = 0.00484) and with a history of adverse vaccination reactions (p = 0.00374) were statistically more likely to observe adverse symptoms after vaccination. CONCLUSIONS: Adverse postvaccinal reactions are relatively common after Comirnaty vaccination but are usually mild and transient in nature. It is in the interest of public health to increase the knowledge of vaccine safety.

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.

COVID-19 in unvaccinated patients with inborn errors of immunity-polish experience.

At the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, patients with inborn errors of immunity (IEI) appeared to be particularly vulnerable to a severe course of the disease. It quickly turned out that only some IEI groups are associated with a high risk of severe infection. However, data on the course of Coronavirus Disease 2019 (COVID-19) in patients with IEI are still insufficient, especially in children; hence, further analyses are required. The retrospective study included 155 unvaccinated people with IEI: 105 children and 50 adults (67.7% and 32.3%, respectively). Male patients dominated in the study group (94 people, 60.6%). At least two comorbidities were found in 50 patients (32.3%), significantly more often in adults (56% vs. 21%). Adult patients presented significantly more COVID-19 symptoms. Asymptomatic and mildly symptomatic course of COVID-19 was demonstrated in 74.8% of the entire group, significantly more often in children (88.6% vs. 46%). Moderate and severe courses dominated in adults (54% vs. 11.4%). Systemic antibiotic therapy was used the most frequently, especially in adults (60% vs. 14.3%). COVID-19-specific therapy was used almost exclusively in adults. In the whole group, complications occurred in 14.2% of patients, significantly more often in adults (30% vs. 6.7%). In the pediatric group, there were two cases (1.9%) of multisystem inflammatory syndrome in children. Deaths were reported only in the adult population and accounted for 3.9% of the entire study group. The death rate for all adults was 12%, 15.4% for adults diagnosed with common variable immunodeficiency, 12.5% for those with X-linked agammaglobulinemia, and 21.4% for patients with comorbidity. The results of our study imply that vaccinations against COVID-19 should be recommended both for children and adults with IEI. Postexposure prophylaxis and early antiviral and anti-SARS-CoV-2 antibody-based therapies should be considered in adults with IEI, especially in those with severe humoral immune deficiencies and comorbidity.

Diagnostic Challenges in Patients with Inborn Errors of Immunity with Different Manifestations of Immune Dysregulation.

Inborn errors of immunity (IEI), formerly known as primary immunodeficiency disorders (PIDs), are inherited disorders caused by damaging germline variants in single genes, which result in increased susceptibility to infections and in allergic, autoimmune, autoinflammatory, nonmalignant lymphoproliferative, and neoplastic conditions. Along with well-known warning signs of PID, attention should be paid to signs of immune dysregulation, which seem to be equally important to susceptibility to infection in defining IEI. The modern diagnostics of IEI offer a variety of approaches but with some problems. The aim of this review is to discuss the diagnostic challenges in IEI patients in the context of an immune dysregulation background.

Serum Allergen-Specific IgE among Pediatric Patients with Primary Immunodeficiency.

Background: Allergy is a clinical condition that reflects a deviated function of the immune system. The purpose of this study was to evaluate serum allergen-specific IgE (sIgE) along with clinical manifestations of allergy in patients with diagnosed primary immunodeficiency (PID). Methods: 72 patients, aged 1−17 years, diagnosed with PID and hospitalized between July 2020 and February 2021 were included in the study. Blood samples were obtained by venipuncture. sIgE (30 allergens), blood eosinophil count, as well as total IgE and IgG were measured and assessed in relation to a detailed medical examination. Results: Serum sIgE was detected in the blood of 50% of the patients in the study group, which significantly correlated (p < 0.0001) with clinical symptoms of allergy. During the period of the study, 61.1% of the patients showed symptoms of allergy, with 77.27% of them having tested positive for sIgE. The total IgE level was elevated in 18.06% of the patients and correlated with clinical symptoms of allergy (p = 0.004). An elevated total IgE level was not observed in children receiving immunoglobulin replacement therapy. Conclusion: The study showed that serum sIgE and total IgE together might be a plausible diagnostic tool for PID patients. However, for patients receiving immunoglobulin replacement therapy, the assessment of total IgE is not useful.

Serum Impedance in Children with Recurrent Respiratory Infections.

The role of disturbed immunoglobulin content during recurrent respiratory tract infections (RTI) might escape recognition in practical children's diagnostics. This study aims to investigate the potential changes in serum impedance caused by a constellation of decreases in the immunoglobulin IgA, IgG, and IgM content in RTI. The control group consisted of children suffering from RTI without any evident decreases in immunoglobulins. Serum bioelectrical properties were measured using impedance spectroscopy and immunoglobulins with an immunoturbidimetric analyzer. We found that the magnitude of serum impedance was significantly smaller in the sick children with immunoglobulin deficiency when compared with those of normal immunoglobulin profile, 134.1 ± 12.8 Ω vs 141.2 ± 16.9 Ω, respectively. We conclude that serum impedance, a parameter easily measured, has the potential to unravel the immunological underlining of RTI, particularly frequent and troubling infections in children. Screening for immunological disturbance is essential for the prompt implementation of a targeted treatment.

Assessment of COVID-19 Incidence and the Ability to Synthesise Anti-SARS-CoV-2 Antibodies of Paediatric Patients with Primary Immunodeficiency.

BACKGROUND: Data regarding the course of SARS-CoV-2 infection in children with primary immunodeficiency (PID) is insufficient. The purpose of the study was to evaluate the morbidity and clinical course of COVID-19 and the ability to produce anti-SARS-CoV-2 IgG antibodies in children with PID. METHODS: In this retrospective study, medical records of 99 patients aged 0-18 were evaluated. The patients were divided into three groups: PID group (68.69%), control group (19.19%) and patients with ongoing or previous paediatric inflammatory multisystem syndrome (12.12%). Data such as morbidity, clinical outcome, and IgG anti-SARS-CoV-2 antibody titres were assessed. RESULTS: A confirmed diagnosis of SARS-CoV-2 infection has been established in 26.47% of patients with PID. Among patients with PID infected with SARS-CoV-2, only three cases were hospitalised. Mortality in the PID group was 0%. Throughout an observation period of 1 year, 47.06% of patients with PID were tested positive for the anti-SARS-CoV-2 antibody. CONCLUSIONS: In the study group, in most cases the disease had a mild and self-limiting course. Remarkably, even though IgG deficiency was the most prevalent form of PID in the study group, the patients were able to respond satisfactorily to the infection in terms of anti-SARS-CoV-2 IgG.

Variants of ATP1A3 in residue 756 cause a separate phenotype of relapsing encephalopathy with cerebellar ataxia (RECA)-Report of two cases and literature review.

BACKGROUND: Variants in ATP1A3 cause well-known phenotypes-alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss (CAPOS), and severe early infantile epileptic encephalopathy. Recently, there has been growing evidence for genotype-phenotype correlations in the ATP1A3 variants, and a separate phenotype associated with variants in residue 756-two acronyms are proposed for the moment-FIPWE (fever-induced paroxysmal weakness and encephalopathy) and RECA (relapsing encephalopathy with cerebellar ataxia). MATERIALS AND METHODS: Herein, we are describing two new pediatric cases with a p.Arg756His change in the ATP1A3 gene. Both patients have had more than one episode of a neurological decompensation triggered by fever with severe hypotonia and followed by ataxia. Thirty-three cases from literature were analyzed to define and strengthen the genotype-phenotype correlation of variants located in residue 756 (p.Arg756His, p.Arg756Cys, p.Arg756Leu). CONCLUSIONS: Patients with a ATP1A3 variant in residue 756 are characterized by recurrent paroxysmal episodes of neurological decompensations triggered by fever, with severe hypotonia, ataxia, dysarthria, symptoms from the orofacial area (dysphagia, drooling) as well as with altered consciousness. Recovery is slow and usually not full with the persistent symptoms of cerebellar ataxia, dysarthria, dystonic and choreiform movements.

Immunoglobulin G Deficiency in Children with Recurrent Respiratory Infections with and Without History of Allergy.

Recurrent respiratory tract infections (RTI) are one of the most common diseases in childhood. Frequent infections adversely affect the development of a child and may lead to suspicion of immunodeficiency. An additional allergy component is thought conducive to infection occurrence. In this study, we retrospectively assessed medical records of 524 children hospitalized with RTI. Patients were divided into two groups: RTI-alone (n = 394) and RTI with a history of allergy (n = 130). Overall, we found that a great majority of children with RTI had the immunoglobulin G within the normal limit, irrespective of allergy. A variable IgG deficiency, most often affecting IgG1, IgG3, and IgG4 subclass, was present in less than one-third of children. Proportions of specific IgG subclass deficiency, varying from about 10% to 40%, were similar in both RTI-alone and RTI-allergy groups. The only significant effect was a modestly smaller proportion of children with IgG4 deficiency in the RTI-allergy group when compared with the RTI-alone group. We also found that IgG deficiencies were age-dependent as their number significantly increased with children's age, irrespective of allergy. The results demonstrate a lack of distinct abnormalities in the immunoglobulin G profile which would be characteristic to a clinical history of allergy accompanying recurrent RTI in children. Thus, we conclude that the assessment of IgGs could hardly be of help in the differential diagnostics of the allergic background of RTI.

Primary Immunodeficiencies: Diseases of Children and Adults - A Review.

Primary immunodeficiencies (PIDs) belong to a group of rare congenital diseases occurring all over the world that may be seen in both children and adults. In most cases, genetic predispositions are already known. As shown in this review, genetic abnormalities may be related to dysfunction of the immune system, which manifests itself as recurrent infections, increased risk of cancer, and autoimmune diseases. This article reviews the various forms of PIDs, including their characterization, management strategies, and complications. Novel aspects of the diagnostics and monitoring of PIDs are presented.

[Recurrent respiratory tract infections in children]. / Nawracajace zakazenia dróg oddechowych u dzieci.

Respiratory diseases are among the most common disorders found in the clinical practice of every pediatrician. It is estimated that a total of 10-15% of children experience recurrent respiratory tract infections (RRTI). Unfortunately, there is no universal consensus on the definition of recurrent respiratory tract infections in children. In addition, the number of episodes taken into account to define the recurrent nature of infections varies depending on the disease (location of the ongoing infection) and its severity. The most commonly accepted definition is the occurrence of eight or more documented respiratory tract infections per year in preschool children (up to three years old) and six or more in children older than three years, in the absence of any pathological condition underlying recurrent infections. It is very important to select in the group of children suffering from RRTI those who may have primary immunodeficiency. The detailed medical history plays an important role. In cases of positive medical history for immunodeficiency, it is mandatory to conduct a detailed examination of the immune system.

Assessment of weight and height of patients with primary immunodeficiency disorders and group of children with recurrent respiratory tract infections.

BACKGROUND: Primary immunodeficiences (PIDs) are a group of chronic, serious disorders in which the immune response is insufficient. In consequence, it leads to an increased susceptibility to infections. Up to date, there are about 350 different disorders classified in that group. There are also patients suffering from recurrent respiratory tract infections (RRTI), however that group doesn't present any abnormalities in terms of conducted immunological tests. Many factors, including medical, can have an impact on physical development of a child. Data such as birth weight and length, also weight, height, BMI during admission to the hospital were collected from 195 patients' medical histories from their hospitalization at Clinical Immunology and Paediatrics Ward of J. Gromkowski Hospital in Wroclaw. Investigated groups included patients with PIDs, RRTI and a control group of healthy children. Our purpose was to evaluate the physical growth of children with PID and children with RRTI by assessment of their height and weight. All of parameters were evaluated using centile charts, suitable best for the Polish population. RESULTS: The lowest mean birth weight and height was found among the PIDs patients group. Children with PIDs during hospitalization had statistically relevant lower mean weight than the control group and almost 18% of them had their height situated below 3rd percentile. The statistically relevant differences have been found between them and RRTI group in terms of weight, height and nutritional status. The statistically significant difference was detected between the nutritional status of PID and control group. CONCLUSIONS: There is a higher percentage of PID patients with physical growth abnormalities in comparison to healthy children. Our findings indicate a need for further investigation of immune system irregularities and their influence on physical growth of children.

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.

[Management of acute gastroenteritis in children]. / Postepowanie w ostrej biegunce infekcyjnej u dzieci.

Acute gastroenteritis is one of the most common infection among children. An estimated 500 million children suffer from the condition worldwide each year. In developed countries the course of acute infectious diarrhea is relatively mild, symptoms usually resolve spontaneously within few days. Unfortunately high mortality rate is still a heavyweight problem in countries with low economic development. Acute diarrhea is defined as a change of the consistency of stools to loose or liquid and/ or increase of an amount of defecations to more than 3 during a day. Other symptoms of gastroenteritis include fever, nausea and vomiting. The most common cause of AGE are viruses, with rotavirus being the most frequent agent. The diagnose is based on medical interview, that include mainly precise information about duration and characteristic of occurred symptoms and epidemiological data. The most important part of diagnostic and therapeutic management is dehydration's assessment, which determine the severity of AGE and is used as one of the factors that decide about hospital admission. The majority of patients can be treated in an outpatients settings, hospitalization should be reserved for those requiring enteral or parenteral rehydration. Oral rehydration with hypoosmolar fluids is standard first-line treatment. Other effective procedures include administration of probiotics (Lactobacillus GG , Saccharomyces boulardii), racecadotril and diosmectite as antidiarrheals and ondansetron reducing the intensity of nausea and vomiting. Antibiotherapy should be only considered in exceptional situations. Acute diarrhea is commonly known medical problem, which can be easily treated by following simple, well-defined rules.

Lung Ultrasonography in the Diagnosis of Pneumonia in Children-A Metaanalysis and a Review of Pediatric Lung Imaging.

BACKGROUND: Pneumonia is one of the most frequent widespread and severe infectious diseases in pediatric patients worldwide. Pneumonia is characterized by high incidence and possibility of complications in the course of the disease in pediatric patients. For this reason, there is a need to have a rapid and safe diagnostic method to recognize it. Imaging diagnostic tools, such as x-ray examinations, necessitate caution while using these methods. To date, there have been lots of studies with the aim to determine the role of lung ultrasonography (LUS) in the diagnosis of inflammatory lesions in children. Our aim was to assess the accuracy of the LUS as diagnostic method of pneumonia in children by making a systematic research of literature. OBJECTIVES: This work is a review of available literature and studies on LUS in pneumonia in children and summary of necessary information about the usefulness of LUS and sonographic findings to diagnose pneumonia in the pediatric population. METHODS: We searched the following databases: PubMed, Scopus, MEDLINE, and Ovid. The following key words were used: pediatrics, pneumonia, ultrasound, chest x-ray, and LUS. RESULTS: The total search results amounted to 1987. From 1987 potentially eligible studies, 19 were included, and 3 were meta-analysis. We studied and performed the statistical analysis of the results publication. CONCLUSIONS: As a result of the analysis, a significant advantage of the ultrasound examination in comparison with the x-ray study was demonstrated. Lung ultrasound could be a safe diagnostic method for this reason.

Disorders of Humoral Immunity in Children with IgG Subclass Deficiency and Recurrent Respiratory Infections.

Respiratory tract infections in children are one of the most common causes for medical consultations. When the infections are of recurring nature, they are a major reason for the diagnostics for primary immunodeficiency that is in about 65% of cases underlain by disorders of humoral immunity. This study seeks to retrospectively evaluate the history of recurrent respiratory tract infections in children with humoral disorders and the associations among deficiencies in the immune system components. We evaluated 394 children aged 3 months to 18 years. We found 49.5% (195 cases) of children with IgG deficiencies, all of whom had normal IgE levels. There were 8.4% (33 cases) of IgA deficiency, 7.4% (29 cases) of IgM insufficiency, and 4.1% (16 cases) of CD19+ cells deficiency. The elevated level of CD19+ cells was found in 27.7% (109 out of the 394 children). Immunoglobulin deficiencies often coexisted with a deficiency in another immunoglobulin class above outlined. There was an interdependence between IgA abnormality and IgG, IgG3, and IgG4 abnormalities as well as between IgM abnormality and IgG and IgG1 abnormalities. We conclude that respiratory tract infections in children are often underlain by a convergence of IgG with both IgA and IgM abnormal states. The physiopathological meaning of this convergence for the infection course and resulting functional respiratory changes remains elusive.

Analysis of differences between total IgG and sum of the IgG subclasses in children with suspected immunodeficiency - indication of determinants.

BACKGROUND: Deficits in disorders of humoral immunity associated with a deficit of antibodies are the most common primary immunodeficiency. Total IgG and IgG subclasses measurements are used to diagnose, differentiate and control in patients with primary and secondary immunodeficiencies. METHODS: The purpose of the study was to analyze the structure patients group according to difference between total IgG and sum of the IgG subclasses and to determine factors affecting the level of this difference. This study was based on data collected from 670 children referred to the Department of Clinical Immunology and Pediatrics in order to diagnose the immune disorders. For all children the level of the total of immunoglobulins IgG and of the IgG subclasses (IgG1, IgG2, IgG3, IgG4) were determined. The group of children was divided into subgroups according to gender, age (under 6 years of age, 6.5-12 years, and 12-18 years), and IgG abnormality (below the normal range, normal and above the normal range). In the patients group, the total IgG values were on average higher than sum of the IgG subclasses. RESULTS: Statistical analysis shown the all parameters under study (age, gender and IgG abnormality) influence statistically significant on the discrepancy between the sum of the IgG subclasses and total IgG. Assessment of IgG and IgG subclasses levels is based on different methods what causes the discrepancy between the sum of the IgG subclasses and total IgG. CONCLUSIONS: Standardization in that regard is crucial. In addition, we have shown the reliability of the results obtained. Despite the determination in two different laboratories and on different analyzers, as well as the freezing process does not affect the test results.

[Paraneoplastic syndromes and rheumatic diseases]. / Zespoly paranowotworowe a choroby reumatyczne.

Paraneoplastic syndromes, which are discussed in this paper, are a heterogeneous group of disorders associated with cancer, but not directly caused by the physical effects of the primary tumor or its metastases. May precede the appearance of the malignant process, occur simultaneously or disclose in the course of cancer. Paraneoplastic syndromes may be caused directly by toxins produced by tumor cells, occur in the course of hypersensitivity reactions, or be the result of release of intracellular antigens. Due to the often similar systemic symptoms it is very important to evaluate the association of rheumatic diseases and cancer. Most paraneoplastic rheumatologic syndroms are difficult distinguishable from idiopathic rheumatologic disorders. The most common paraneoplastic syndromes include rheumatoid arthritis (RA)-like syndrome arthritis, inflammatory myopathies, hypertrophic osteoarthropathy, vasculitis and Raynaud's phenomenon.

Ten new ATM alterations in Polish patients with ataxia-telangiectasia.

Inherited biallelic mutations of the ATM gene are responsible for the development of ataxia telangiectasia (AT). The objective of the present study was to conduct molecular analysis of the ATM gene in a cohort of 24 Polish patients with ataxia-telangiectasia with aim being to provide an updated mutational spectrum in Polish AT patients. As a result of molecular analysis, the status of recurrent mutation was confirmed and ten new ATM variants were detected. Application of MLPA analysis allowed the detection of large genomic deletion. Previously, this type of mutation had never been seen in our population. Finally, in silico analysis was carried out for newly detected ATM alterations. In addition, functional analysis was performed to evaluate the effects of intronic variants: c.3402+30_3402+32delATC.