The potential anti-inflammatory role of adiponectin in food allergy: a case-control study on children.

We aimed to assess the possible relationship between food allergy and two key adipokines - leptin and adiponectin - in children with food allergy. A total of forty patients with definite diagnosis of food allergy according to clinical history and specific IgE (sIgE) for food allergens (group I) were enrolled in this pilot study. The control group (group II) included thirty children with no evidence of allergic symptoms. Serum levels of leptin and adiponectin were measured by ELISA. Meanwhile, sIgE was measured for the eight most common food allergens by the immunoblot method in all participants. The median ages in groups I and II were 18·5 and 23·5 months, respectively. The respective Caesarean section rate was 64·9 and 16·7 % in groups I and II (P<0·001). Serum levels of adiponectin were significantly higher in the patient group compared with controls (24·11 (sd 12·14) v. 10·67 (sd 12·23) µg/ml, P<0·001), whereas no statistically meaningful difference was detected in serum leptin concentrations (P=0·92). There was a significant inverse relationship between age and adiponectin levels in group I (P=0·002, r -0·479) and group II (P=0·04, r -0·365), and it was more significant in group I. The most common allergens in the patient group were wheat (52·5 %), hazelnut (52·5 %), cow's milk (50 %) and egg white (30 %). The results of this study suggest an essential link between adiponectin and food allergy that is probably unlikely to be affected by obesity as a confounding factor.

The Critical Role of Prenatal Genetic Study in Prevention of Primary Immunodeficiency in High-risk Families: The Largest Report of 107 Cases.

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases.

Outcome of allogeneic Hematopoietic Stem Cell Transplantation on Diamond-Blackfan anemia using busulfan-based myeloablative regimen.

Behfar M, Koochakzadeh L, Yazdanian N, Salajegheh P, Rostami T, Khodayari-Namini N, Ghavamzadeh A, Hamidieh AA. Outcome of allogeneic Hematopoietic Stem Cell Transplantation on Diamond-Blackfan anemia using busulfan-based myeloablative regimen. Turk J Pediatr 2019; 61: 407-412. Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only known curative option for hematologic manifestations of Diamond-Blackfan anemia (DBA) as a rare inherited bone marrow failure syndrome. This treatment may be considered for DBA patients with corticosteroid-resistance, transfusion dependence, and/or progression to severe aplastic anemia or myelodysplastic syndrome (MDS)/ Acute myleloid leukemia (AML). In this prospective study, 10 pediatric DBA patients (age < 15 years) who underwent allo-HSCT from HLA-matched donors using non-TBI myeloablative conditioning regimen (intravenous busulfan and cyclophosphamide ± antithymocyte globulin) during September 2010 to February 2014 are reported. For Graft versus Host Disease (GvHD) prophylaxis cyclosporine A. and a short course of methotrexate were administered. Except one patient who received transplantation from his sibling cord blood, engraftment occurred in all the other patients (9 out of 10) with full donor chimerism ( > 95%). The median neutrophil and platelet engraftment times were 11 (range, 10- 13) days and 23 (range, 15-50) days, respectively. Acute GvHD developed in 7 patients. After a median follow-up of 53.3 months, 8 patients are still alive, of whom 7 patients are disease-free. The other two patients died due to grade III-IV acute GvHD. Our data suggests that allo-HSCT using busulan-based non-TBI myeloablative conditioning regimen could be a long-term effective treatment for DBA patients. Early transplantation especially before having multiple transfusions leading to iron overload, particularly from an HLAmatched sibling donor would be associated with favorable outcomes.

Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D.

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder of immune dysregulation. FHL inherited in an autosomal recessive pattern is classified into five subtypes based on underlying genetic defects. Mutations in four genes including PRF1, UNC13D, STX11 and STXBP2 are responsible for FHL2 to FHL5 respectively. The cause of FHL1 is associated with mutations in an unknown gene located at 9q21.3-22. This study aims to report the clinical features and genetic results of nine Iranian patients suffering from -haemophagocytic lymphohistiocytosis. Nine patients (five males and four females) suspected to FHL whose genetic evaluation of PRF1 and STX11 revealed no mutations, were entered the study to investigate UNC13D mutations. Primers were designed to amplify all coding regions and exon-intron boundaries of the gene. PCR products were then sequenced and analyzed by sequence analysis tools including BLAST. The most frequent clinical manifestations observed in the patients were fever and hepatosplenomegaly. In this study, five mutations were detected in UNC13D including four novel mutations (c.1434_1446delACCCATGGTGCAGinsTGGTGCT, c.1933C>T, c.1389+1G>C and c.2091+1G>A) besides to a previously reported deletion (c.627delT). The pathogenicity of the missense mutation was assessed using online prediction tools including SIFT and PolyPhen2. The study results may provide valuable information for genetic counseling especially for those who have a history of immunodeficiency diseases in their family and can be used for prenatal diagnosis.