Relation between dysbiosis and inborn errors of immunity

Inborn errors of immunity(IEI)disorders,formerly primary immune deficiency diseases,are a heterogeneous group of disorders with variable hereditary transitions,clinical manifestations,complications and varying disease severity.Many of the clinical symptoms,signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity(dysbiosis).For example,in common variable immunodeficiency patients,the diversity of bacteria,but not fungi,in the gut microbiota has been found to be reduced and significantly altered.Again,this was associated with a more severe disease phenotype.Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients,causing Candida albicans to switch from commensal to pathogenic.Modification of the microbiota can be used as a therapeutic approach in patients with IEI.Prebiotics,probiotics,postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients.Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.

Mast cell activation syndrome:An up-to-date review of literature

Mast cells are a subtype of white blood cells and are involved in the immune system.These cells contain many chemical substances called mediators,which are involved in the allergic response.The fact that mast cells play a role in many events that require urgent intervention,especially anaphylaxis,has led to a more detailed study of these cells.The diseases also caused by dysfunctions of mast cells have been examined in many circumstances.For instance,mast cell activation syndrome is known as an augmented number of cells due to decreased cell death,resulting in clinical symptoms affecting many systems.The main common symptoms include flushing,hypotension,urticaria,angioedema,headache,vomiting and diarrhea.Although the underlying mechanism is not yet clearly known,we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.

COVID-19 and cardiac complications:Myocarditis and multisystem inflammatory syndrome in children

Coronavirus is an important pathogen causing disease in humans and animals.At the end of 2019,an investigation into an increase in pneumonia cases in Wuhan,Hubei Province,China,found that the cause was a new coronavirus.This disease,which spread rapidly across China and caused an outbreak worldwide,resulted in a pandemic.Although this virus has previously been referred to as 2019-nCoV,which causes coronavirus disease 2019(COVID-19),later it was named severe acute respiratory syndrome coronavirus 2.Children were usually asymptomatic and rarely severely affected.In April 2020,reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome.This clinical picture was later defined as multisystem inflammatory syndrome in children.Since then,similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world.In this review,we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

Case of purine nucleoside phosphorylase deficiency presented with hematuria

Purine Nucleoside Phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder. In PNP-deficiency disorder, the deficient enzyme leads to accumulation of toxic metabolites, especially in lymphocytes and the metabolites exert toxic effect on T-cell generation. Purine nucleoside phosphorylase deficiency causes decreased numbers of T cells and lymphopenia. The patients suffering from PNP-deficiency may be admitted with recurrent infections, as well as neurological and autoimmune findings. We hereby presented a case admitted with the symptom of hematuria in which we established the diagnosis of PNP-deficiency early on the basis of detection of lymphopenia and low level of uric acid.

COVID-19 frequency and clinical course in children with asthma

BACKGROUND The epidemic of severe acute respiratory syndrome coronavirus 2 infection,known as the coronavirus disease 2019(COVID-19),has caused a global health concern.Since its emergence,numerous studies have focused on various clinical manifestations and outcomes in different populations.However,studies are ongoing as the consequences and impact of COVID-19 in children with chronic diseases such as asthma are controversial.AIM To fill this research gap by retrospectively evaluating the course,laboratory,and clinical findings of COVID-19 among 414 asthmatic children followed up from the pediatric allergy outpatient clinic and known to have had COVID-19.METHODS The data of 5510 patients over the age of 5 diagnosed with asthma in our hospital's data were retrospectively scanned with specific parameters using protocol numbers from the hospital filing system.The data included retrospective evaluation of pulmonary function test results before and after COVID-19,routine hematological and biochemical parameters,sensitization states(total IgE,specific IgE,and skin prick test results),and radiological(computed tomography)findings.To inquire about the course and symptoms of COVID-19,asthma patients or their parents were then called and evaluated with a questionnaire.RESULTS As a result of retrospectively scanning the data of 5510 asthma patients over the age of 5,it was determined that 414(7.5%)patients had COVID-19.The mean age of 414 patients was 17.18±4.08(min:6;max:28)years.Two hundred and three of our 414 patients are male,and 211 are female.When their vaccination status was questioned,21.5% were vaccinated.When the symptoms of our 290 patients were questioned,it was stated that 59.0% had fever symptoms.The rate of using regular prophylactic asthma medications was 19%.The rate of using salbutamol in asthma was found to be 22%.The rate of patients using methylprednisolone was 1%.Emergency service admission was 17.2%,and hospitalization was found to be 4.8%.Leukopenia(<4000)was found in 14.1%of patients,and 8.08% of our patients had neutropenia(<1500).Lymphopenia(<1500)was detected in 44.4% of patients,and lymphocytosis(>4000)was found in 5.05% of patients.In 65% of our patients,the C-reactive protein value was elevated.A high aspartate aminotransferase and alanine aminotransferase value was detected in 3.2% and 5.4% of patients were found,respectively.31%of patients had an elevated lactate dehydrogenase value.Typical radiological findings for COVID-19 were detected in 3/309 of patients.CONCLUSION According to our study,there is a correlation between the severity of COVID-19 and asthma symptoms and the course of the disease.However,it is worth noting that the retrospective nature of the study and the differences in sample size,age,and demographic characteristics between the two groups do not allow for an optimal comparison.Therefore,further investigation is needed to explore the relationship between COVID-19 and asthma,and it can be suggested that COVID-19 may trigger asthma attacks and asthma may impact the course of COVID-19.

Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis

Background Overexpression of the components of the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis(sJIA).The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA.Methods Total RNA was extracted from peripheral blood mononuclear cells(PBMCs)in active JIA patients.The relative expressions of miR-21,STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay.Rheumatoid arthritis fibroblast-like synovial cell(RASF)was stimulated to become to osteoclasts using macrophage colony-stimulating factor(M-CSF)and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21.The expression of STAT3/p-STAT3 was measured by western blot,and the levels of interleukin(IL)-17A,p65,matrix metalloproteinases(MMP)-3,MMP-4 and receptor activator of nuclear factor-κd3 after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay.Finally,the miR-21 targeted STAT3 gene was detected by the dualluciferase reported assay.Results The expression of miR-21 was significantly lower in JIA patients than in healthy control(P<0.05).The level of STAT3 was increased in PBMCs of JIA group compared with control group(P<0.05).Furthermore,the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3(r=-0.5854/r=-0.6134,P<0.05).The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21.The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21(P<0.05).RASFs were induced into osteoclasts using M-CSF.The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group(P<0.05).Conclusions We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control.MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3.MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.

An unusual cause of an anterior mediastinal mass in a 52-day-old infant with mediastinal tuberculosis

Tuberculosis(TB)continues to be one of the major infectious diseases threatening millions of lives worldwide.[1]We encountered a 52-day-old male infant with a anterior mediastinal mass caused by tuberculosis.On admission to our hospital,the infant presented with respiratory distress,wheezing,fever,and cough.Decreased breath sounds were audible at the apex of the left chest.His temperature was 38.2℃.

Disease tolerance to infection: the immune defense strategy of mitoribosome targeting

“In the practice of tolerance,one’s enemy is the best teacher”.-Sayings of Buddhism.To survive an infection,two evolutionarily conserved defense strategies are required for infected host survival.One strategy in volves acquiri ng resista nee by reduci ng pathogen load via pathoge n recog nition,signaling tran sducti on pathways,and effector mechanisms.Another strategy involves increasing disease tolerance by eliciting tissue damage control mechanisms,which adjust the metabolic output of host tissue in response to different forms of stress and damage.Hence,in recent research,disease tolera nee is regarded as an in here nt comp onent of immunity,which does not exert a direct impact on pathogens but is essential to limit the health and fitness costs of infection;however,its molecular bases remain poorly understood.