Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Serum sickness-like reactions in Iranian children: a registry-based study in a referral center.

INTRODUCTION AND OBJECTIVES: Considering that no studies have been done on a comprehensive review of Serum sickness-like reactions patients (SSLRs) at a referral center in Iran so far, this study aimed to determine the clinical and laboratory characteristics of children with SSRL in Tehran Children's Medical Center. PATIENTS: The present study was a registry-based study in which the data of 94 SSLRs patients registered in a two-year period were investigated. Confirmation of fever, rash, urticaria, arthralgia / arthritis and history of antibiotic consumption up to three weeks before were the criteria for the diagnosis. RESULTS: Fifty-one (54 %) patients were male with mean age of 56 ±â€¯30 months and there was no significant difference in the age of the two genders. The mean onset of symptoms before hospitalization were 3.8 ±â€¯2.7 days (1-14 days); this mean was significantly higher in males than in females (4.6 ±â€¯2.9 versus 2.9 ±â€¯1.7 days, P-value = 0.003). Among antibiotics, Co-amoxiclav and Cefixime antibiotics had the most frequency by 31 % and 33 %, respectively as the most important incidence factor of SSLRs. The mean duration of consumption of culprit medications in the incidence of SSLRs was 5.6 ±â€¯2.9 days with a range of 1-15 days. CONCLUSIONS: This study showed that among the antibiotics, Co-amoxiclav and Cefixime are more prevalent and a review of prescribing these two antibiotics for the treatment of the children's infections is essential if this finding is confirmed by other Iranian scholars.

Evaluation of dynorphin and kappa-opioid receptor level in the human blood lymphocytes and plasma: Possible role as a biomarker in severe opioid use disorder.

BACKGROUND: The dynorphin (DYN)/kappa opioid receptor (KOR) system plays an important role in the development of addiction, and dysregulation of this system could lead to abnormal activity in the reward pathway. It has been reported that the expression state of the neurotransmitters and their receptors in the brain is reflected in peripheral blood lymphocytes (PBLs). METHODS: We have evaluated the PBLs and plasma samples of four groups: 1) subjects with severe opioid use disorder (SOD), 2) methadone-maintenance treated (MMT) individuals, 3) long-term abstinent subjects having former SOD, and 4) healthy control subjects (n = 20 in each group). The mRNA expression level of preprodynorphin (pPDYN) and KOR in PBLs has been evaluated by real-time PCR. Peptide expression of PDYN in PBLs has been studied by western blot, and DYN concentration in plasma has been measured by ELISA. RESULTS: The relative expression level of the pPDYN mRNA and PDYN peptide in PBLs were significantly up-regulated in SOD, MMT, and abstinent groups compared to control subjects. No significant difference was found in the plasma DYN concentration between study groups. The expression level of the KOR mRNA in PBLs was significantly decreased in all three study groups compared to the control subjects. CONCLUSION: the expression changes in the DYN/KOR system after chronic exposure to opioids, including methadone, seems to be stable and does not return to normal levels even after 12 months abstinence. These long-time and permanent changes in PBLs may serve as a biomarker and footprint of SOD development in the periphery.

Effect of Synbiotic on the Treatment of Jaundice in Full Term Neonates: A Randomized Clinical Trial.

PURPOSE: Jaundice accounts for most hospital admissions in the neonatal period. Nowadays, in addition to phototherapy, other auxiliary methods are used to reduce jaundice and the length of hospitalization. This study aimed to investigate the effect of probiotics on the treatment of hyper-bilirubinemia in full-term neonates. METHODS: In this randomized clinical trial, 83 full-term neonates, who were admitted to the hospital to receive phototherapy in the first 6 months of 2015, were randomly divided into two groups: synbiotic (SG, n=40) and control (CG, n=43). Both groups received phototherapy but the SG also received 5 drops/day of synbiotics. Serum bilirubin, urine, stool, feeding frequency, and weight were measured daily until hospital discharge. A p-value<0.05 was considered statistically significant. RESULTS: The mean total serum bilirubin in the SG was lower than that in the CG (9.38±2.37 and 11.17±2.60 mg/dL, respectively). The urine and stool frequency in the SG was significantly higher than that in the CG (p<0.05). The duration of hospitalization in the SG was shorter than that in the CG. CONCLUSION: Use of synbiotics as an adjuvant therapy had a significant treatment effect on jaundice in full-term neonates. Further studies including larger samples with long follow-up periods are essential to confirm the benefits of routine use of synbiotics in neonatal patients with jaundice.

The Lowering of Bilirubin Levels in Full-Term Newborns by the Effect of Combined Massage Therapy and Phototherapy Practice.

OBJECTIVE: Various therapeutic treatments have been prescribed for decreasing the bilirubin level. Massage therapy is one of the neonate treatments for jaundice. The aim of this study is to investigate the effects of combined massage therapy and phototherapy on neonatal jaundice. STUDY DESIGN: This study was performed at Shahid Madani Hospital in the city of Khorramabad in 2016, where 83 healthy full-term infants were enrolled. They were selected through convenience sampling and then were randomly assigned to the intervention and control groups. The control group (n = 43) received phototherapy, whereas infants in the intervention group (n = 40) received 4 days of massage and phototherapy. The serum bilirubin level, frequency of stooling and amount of urination, duration of hospitalization, and feeding frequency were analyzed using SPSS by descriptive and analytical statistics (mixed regression models). RESULTS: Baseline levels of bilirubin were similar between the two groups (p > 0.05). The bilirubin level was measured as 13.4 ± 0.7 mg/dL in the intervention group on day 1. It stood at 14.4 ± 1.5 mg/dL in the control group, which was not statistically significantly different. However, the mean bilirubin level was decreased on day 4 of hospitalization to 7.4 ± 0.56 mg/dL and 9.0 ± 2.3 mg/dL, showing a significant difference decrease in the intervention and control group (p < 0.05), respectively. CONCLUSION: Intervention had a significant role in decreasing the bilirubin level, amount of urination, and duration of hospitalization of full-term infants suffering from hyperbilirubinemia.

Treating Viral Diarrhea in Children by Probiotic and Zinc Supplements.

PURPOSE: The aim of this study was to analyze the effects of probiotics and zinc supplements on the mean duration and frequency of acute diarrhea in children aged 6 months to 2 years. METHODS: In this clinical trial of infants aged between 6 months and 2 years, eligible patients were divided into 3 groups: Zinc Receiving Group (ZRG), Probiotic Receiving Group (PRG), and a control group receiving supportive care alone. The frequency of diarrhea was evaluated in the test groups during the first 24 hours and 48-72 hours, along with the duration of hospitalization and diarrhea persistence for 3-7 days. RESULTS: Diarrhea persisted for until the third day of admission in 100% of the infants in PRG compared with only 76.1% in ZRG. The relative risk of diarrhea persistence in the PRG was 1.31 times more than in ZRG until the third day. Also, 80% of diarrhea cases in the PRG persisted until the fourth day of admission, compared with 47.8% in the ZRG group, and this value was significant. The relative incidence of diarrhea persistence in the PRG was 36.4 times greater than in the ZRG until the day 4. Also, the percentage of post-treatment complications was 35.5% in the PRG and 2.6% in the ZRG, which was significant. CONCLUSION: In our study, the effectiveness of zinc at a dose of 20 mg was higher than that of probiotics. The complications associated with zinc supplementation were lower than those of probiotics.

Echocardiographic Evaluation in Neonates with Heart Murmurs.

Auscultation of the heart is one of the most important tools of physical examination in neonates, which is very helpful in the diagnosis or rejection of congenital heart diseases (CHDs). The aim of this study is to investigate the causes of heart murmur in neonates hospitalized in neonatal unit in Imam Reza Hospital, Kermanshah, Iran. This cross-sectional study was conducted within the period of 18 months on neonates hospitalized in neonatal unit whose heart murmur, diagnosed through examination, and echocardiography was conducted to investigate the existence of CHD. In 62.1% of the cases, murmuring was auscultated within the first week after birth. Among 172 neonates with heart murmur, 25 subjects (14.5%) had normal echocardiogram, and others had abnormal echocardiogram in which ventricular septal defect (31.4%) was the most common CHD. Patent ductus arteriosus (23.3%) was the second common CHD found. Other defects were atrial septal defect, persistent foramen ovale, pulmonary stenosis, and tricuspid regurgitation. Among the neonates with CHD, 55 subjects were females and 92 cases were males. There was CHD history in previous siblings in 10 cases. In 73 neonates with CHD, the mother had not taken folic acid in the first trimester of pregnancy. A total of 14.5% of the hospitalized neonates suffered from innocent murmur, and the rest with heart murmur had abnormal echocardiography and suffered from CHD (85.5%). Heart murmur in neonates could be a symptom of CHD, and timely echocardiography is very important in diagnosing the type of disease.

Study of behavioural disorders in children with primary enuresis.

BACKGROUND: Enuresis results in behavioural disorder in children. This study investigated the behavioural disorders in children possessing primary enuresis. MATERIALS AND METHODS: In this cross-sectional study, 100 children with primary enuresis were referred to children's hospital Khorramabad; the census method was used in this study. Data were collected using a short screening instrument for enuresis psychological problems, the reliability and validity of which have been confirmed in previous studies. First, a questionnaire was used to assess academic failure, anxiety, behavioural disorders, sleep, and psychological disorders. Results obtained were compared in terms of gender and age. Statistical analyses using inferential and descriptive statistics including Chi-square and Fisher test were employed. RESULTS: The average age of children was 8.46 years. Sixty-six per cent of participants were male and the rest of them were female. Ninety per cent of subjects were between the age range of 1-9 years, and 10% were over 10 years old. Forty-three per cent of children suffered from anxiety disorders and 34% had sleep disorders, 4% also suffered from academic failure. Among behavioural disorders, hyperactivity and restlessness were the most common disorders, and they were significantly higher in nine boys. Headache, obsessive, and sleep disorders were more common in children above 10. There was a significant correlation between eating disorders, headache, sleep disorders, and strange movements in males, while feelings of sadness were more common in females. CONCLUSION: Social personality development in children with enuresis can be improved by informing parents of enuresis.

Prevalence of anemia and its risk factors among pregnant women in Khorramabad (Iran) 2010-2014.

PURPOSE: Anemia's adverse effects on physical and behavioral development and on the reduction of efficiency have been proven. The aim of this study was to determine the prevalence of anemia in pregnant women referred to the health care centers of Khorramabad from 2010 to 2014. MATERIALS AND METHODS: In this cross-sectional study, 2821 prenatal care cases of pregnant women referred to health care centers of Khorramabad were studied. Studied variables included the following: hemoglobin, hematocrit, age, parity, trimester of pregnancy status, number of deliveries, number of abortions, number of children, weight, height, time gap from previous delivery, negative RH, history of eclampsia/preeclampsia, coagulation disorder and blood pressure. RESULTS: The mean age of the studied women was 26.7 ± 5.5. The mean levels of hemoglobin and hematocrit from the population was 12 ± 1.1 and 36.1 ± 9.2, respectively. The prevalence of anemia was 16.8%. Prevalence of anemia among pregnant women referred to health care centers of Khorramabad was found to be high. CONCLUSIONS: Staff working at different parts of health care centers were advised to pay more attention to this problem. They should also try to control and treat anemia by regular distribution of iron supplements among women referred to health care centers.