TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases.

BACKGROUND: A20 haploinsufficiency (HA20) is a newly introduced autosomal dominant autoinflammatory disorder, also known as Behcet's-like disease. Some of the most common symptoms of the disease are recurrent oral, genital, and/or gastrointestinal (GI) ulcers, episodic fever, musculoskeletal symptoms, cutaneous lesions, and recurrent infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of multi-organ failure due to excessive immune activation. HLH has been reported in a few HA20 patients. Herein, we report two children with the primary presentation of HLH, with a mutation in TNFAIP3, in favor of HA20. CASE PRESENTATIONS: Our first patient was a 4-month-old boy who presented with fever, irritability, pallor, and hepatosplenomegaly. Pancytopenia, elevated ferritin, and decreased fibrinogen levels were found in laboratory evaluation. He was diagnosed with HLH and was treated with methylprednisolone and cyclosporine. Two years later, whole exome sequencing (WES) indicated a mutation in TNFAIP3 at NM_001270507: exon3: c.C386T, p.T129M, consistent with A20 haploinsufficiency. Etanercept, a TNF inhibitor, was prescribed, but the parents were reluctant to initiate the therapy. The patient passed away with the clinical picture of cerebral hemorrhage. The second patient was a 3-month-old boy who presented with a fever and hepatosplenomegaly. Laboratory evaluation found pancytopenia, hyperferritinemia, hypoalbuminemia, hypertriglyceridemia, and hypofibrinogenemia. With the establishment of the HLH diagnosis, he was treated with etoposide, dexamethasone, and cyclosporine, and recovered. WES results revealed a heterozygous de novo variant of TNFAIP3 (c. T824C in exon 6, 6q23.3) that leads to a proline to leucine amino acid change (p. L275P). He was treated with etanercept and has been symptom-free afterward. CONCLUSIONS: This report is a hypothesis for developing of the HLH phenotype in the presence of TNFAIP3 mutation. Our results provide a new perspective on the role of TNFAIP3 mutation in HLH phenotypes, but more extensive studies are required to confirm these preliminary results.

Evaluation of the risk of malnutrition in hospitalized children by PYMS, STAMP, and STRONGkids tools and comparison with their anthropometric indices: a cross-sectional study.

BACKGROUND: Malnutrition is a determining factor of pediatric mortality and morbidity, especially in low and middle-income countries. Hospitalized children are at a higher risk of malnutrition. Several malnutrition screening tools have been used, among which STAMP, PYMS, and STRONGkids are valid tools with high sensitivity and specificity. The aim of this study was to compare these screening tools to find the best ones in identifying the risk of malnutrition in hospitalized children. METHODS: This is a cross-sectional study performed on hospitalized children aged 1 to 16 years. The questionnaires of PYMS, STAMP, STRONGkids malnutrition risk assessment tools were filled. The weight for height and BMI for age Z-scores were calculated. The data were analyzed by SPSS. Sensitivity, specificity, positive predictive value, and negative predictive values of the risk scores based on weight for height and BMI for age Z-scores were calculated. RESULTS: Ninety-three patients with a mean age of 5.53 ± 3.9 years were included. The frequency of malnutrition was reported as 26% and 39% according to weight for height and BMI for age Z-scores, respectively. A significant relationship was found between PYMS and Weight for height Z-score (P-value < 0.001), and BMI for age Z-score (P-value < 0.001). Moreover, STRONGkids was found to be associated with weight for height Z-score (P-value: 0.017). CONCLUSION: The PYMS is a practical and beneficial tool in early identifying the risk of severe malnutrition in hospitalized patients. It is a suitable method for patients in our settings.

Management of Inborn Errors of Immunity in the Genomic Era.

Inborn errors of immunity are a group of rare diseases characterized by a wide variety of manifestations, including unusually severe infections, cancer susceptibility, and exaggerated inflammation that disrupts organ function. As of 2022, over 450 gene deficiencies have been classified under ten categories, where numbers are constantly increasing. The range of inborn errors of immunity varies considerably, from mild infections to serious multisystemic disease. Whereas patients with T cell defects are liable to a broad range of pathogens, selected inborn errors of immunity may predispose hosts merely to a narrow range of microorganisms. Dysregulated immune responses often cause autoimmune manifestations that may target any organ or lead to severe allergies. Therefore, presentation to any medical discipline is possible. Historically, inborn errors of immunity have been associated with short life expectancy and poor life quality, but intensive research into the field has revolutionized this assumption. Especially with the aid of translational investigations, our clinical practice has transformed from a predominantly phenotype-driven management into one that is reinforced by an etiology-driven therapy. This review summarizes the recent advances in molecularly targeted treatment approaches in various inborn errors of immunity conditions, with many success stories corroborating the power of genomic medicine. The principles of applications learned from these rare monogenic traits, in which the functional impact of the molecular pathways is clear-cut, may be instructive for developing basic concepts toward precision therapy of the common immune-mediated disorders, including autoimmunity, infectious diseases, and allergy, which affect mass populations.

Role of serology tests in COVID-19 non-hospitalized patients: A cross-sectional study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus (SARS-CoV2) has imposed catastrophic impressions on the world. After all the focused researches conducted in the COVID-19 area, many features remain obscure. We have surveyed 1,363 outpatients with suspected COVID-19 in Tehran, Iran. The analysis emphasized on characteristics of patients with positive PCR or serology of SARS-CoV-2. METHODS: The nasopharyngeal swabs were tested for SARS-CoV2 PCR. Serum specimens were tested for SARS-CoV2 IgG and IgM. Clinical presentations of the patients, history of chronic diseases or drug use, contact with a possible COVID-19 patient and previous infection with SARS-COV2 were investigated. RESULTS: Of the total 1,363 investigated patients, 22% had positive SARS-CoV-2 PCRs, 82% had positive IgG, 38% had positive IgM, and 31% had both positive IgM and IgG values. Positive serologic tests were significantly associated with a positive PCR test obtained previously in the course of the current disease (P value<0.001). IgG and IgM antibody values were significantly associated with underlying disease, cough, fever, chills, fatigue, and myalgia (all P values <0.001). Dyspnea was significantly associated with IgG levels (P value = 0.01), yet it was not associated with IgM serology (P value = 0.2). Positive serology tests were not associated with symptoms of coryza. GI symptoms were not associated with positive IgG test (P value = 0.1), yet it did show an association with positive IgM test (P value = 0.02). Cough, fever, chills, myalgia fatigue, dyspnea, and GI symptoms were all significantly associated with positive PCR (all P values <0.001), and symptoms of coryza did not show a significant relationship (P value = 0.8). CONCLUSION: Assessing antibody titers in outpatients is invaluable due to the epidemiological importance of investigations in mild or even asymptomatic cases. Since the number of such studies in non-hospitalized patients is not high, the current study can be used as a comparison model.