I accidentally stayed alive

U seriji od pet knjiga "Mi smo preživeli: Jevreji o Holokaustu" od kojih su tri prevedene na engleski jezik, sakupljena su svedočenja malobrojnih preživelih članova jevrejske zajednice o vremenu Drugog svetskog rata. Osobenost prilika u kojima se zateklo celokupno stanovništvo Kraljevine Jugoslavije ogleda se u činjenici da je tu državu, početkom rata, okupiralo pet zavojevača: Nemačka, Italija, Bugarska, Mađarska, Albanija i fašistička satelitska tvorevina, tzv. Nezavisna država Hrvatska. Te okolnosti su uslovile i različite načine preživljavanja i spašavanja Jevreja sa ovih prostora. Jevrejski istorijski muzej Saveza jevrejskih opština Jugoslavije/Srbije objavio je ove knjige uz pomoć donacija i uz volonterski rad redakcije u kojoj je sedam od devet članova preživelo Holokaust. One čine izuzetnu kolekciju tragičnih i dramatičnih iskustava o jedinstvenom izboru – borbi za život, dostojanstvo i slobodu u partizanima; o koncentracionim logorima, o izbegličkom životu pod stalnom pretnjom, o pomoći i prijateljstvima. One su i dobra podloga za istraživanje Holokausta i istorije Jevreja sa tla bivše Jugoslavije. Svako svedočenje je obogaćeno nizom fotografija i zajedno sa tekstom čine jedinstveni dokumentacioni materijal. Kako je stradanje Jevreja na tlu bivše Jugoslavije slabo poznato široj publici, ove knjige imaju zadatak da ispune taj prostor. One tako postaju spomenik za sve stradale čija se mnogobrojna imena nalaze samo u sećanjima. Jedno od tih sećanja je "Slučajno sam ostao živ" Ješue Abinuna.In five books, "We Survived: Yugoslav Jews on the Holocaust" (three of them translated into English), the testimonies of a small number of surviving members of the Jewish community about World War II were collected. The peculiarity of the circumstances in which the entire population of the Kingdom of Yugoslavia was found is reflected in the fact that at the beginning of the war, the country was occupied by five invaders: Germany, Italy, Bulgaria, Hungary, Albania and the fascist satellite formation, the so-called The Independent State of Croatia. These circumstances also led to different ways of surviving and rescuing Jews from these areas. The Jewish Historical Museum of the Federation of Jewish Communities of Yugoslavia / Serbia published these books with help of donations and volunteer work of the editorial board in which seven of nine members survived the Holocaust. These books are an extraordinary collection of tragic and dramatic experiences about unique choices - the struggle for life, dignity, and freedom in partisans; about concentration camps, about refugee life under constant threat, about help and friendships. They are also a good basis for exploring the Holocaust and the history of Jews from the former Yugoslavia. Each testimony is enriched with a series of photographs and together with the text, they make unique documentation material. As the suffering of Jews on the territory of the former Yugoslavia is poorly known to the general public, these books have the task of filling that space. They thus become a memorial for all the victims whose many names are found only in memory. One of those memories is "Slučajno sam ostao živ" (I accidentally stayed alive) by Ješua Abinun

Slučajno sam ostao živ

In five books, "We Survived: Yugoslav Jews on the Holocaust" (three of them translated into English), the testimonies of a small number of surviving members of the Jewish community about World War II were collected. The peculiarity of the circumstances in which the entire population of the Kingdom of Yugoslavia was found is reflected in the fact that at the beginning of the war, the country was occupied by five invaders: Germany, Italy, Bulgaria, Hungary, Albania and the fascist satellite formation, the so-called. The Independent State of Croatia. These circumstances also led to different ways of surviving and rescuing Jews from these areas. The Jewish Historical Museum of the Federation of Jewish Communities of Yugoslavia / Serbia published these books with the help of donations and volunteer work of the editorial board in which seven of nine members survived the Holocaust. These books are an extraordinary collection of tragic and dramatic experiences about unique choices - the struggle for life, dignity, and freedom in partisans; about concentration camps, about refugee life under constant threat, about help and friendships. They are also a good basis for exploring the Holocaust and the history of Jews from the former Yugoslavia. Each testimony is enriched with a series of photographs and together with the text, they make unique documentation material. As the suffering of Jews on the territory of the former Yugoslavia is poorly known to the general public, these books have the task of filling that space. They thus become a memorial for all the victims whose many names are found only in memory. One of those memories is "I stayed alive by coincidence" by Ješua Abinun

Hematopoietic stem cell transplantation and vasculopathy associated with STAT3-dominant-negative hyper-IgE syndrome

Dominant negative mutations in the transcription-factor STAT3 underlie the rare primary immunodeficiency Job's syndrome. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has shown promise in correction of the underlying immunological defect, with one report suggesting HSCT can prevent development of wider connective tissue complications. Here, we report the case of a 26 year old male who developed an acute ST-elevation myocardial infarction due to coronary artery ectasia and thrombosis, occurring despite pediatric allogeneic HSCT for STAT3-HIES and a predicted 10-year conventional cardiovascular risk of 0.1%. Vasculopathy associated with STAT3-HIES may persist or arise following HSCT and can precipitate life-threatening complications. This has implications for counseling and vascular surveillance, and highlights the need for further studies to determine the risk, pathogenesis, and optimal management of the vasculopathy associated with STAT3-HIES

Immunological characteristics and T cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T cell depleted autologous stem cell transplantation.

Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk of from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T cell depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission post ASCT is unknown. Immune reconstitution of T, B, NK, NK-T cell and monocytes, in parallel with T cell receptor diversity by analysis of beta variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in 5 children with sJIA before and after ASCT. At time of follow up (mean 11.5 years), 4 patients remain in complete remission, while 1 child had relapsed within 1 month of transplant. The CD8(+) TCRVb repertoire was highly oligoclonal early in immune reconstitution and re-emergence of pre-transplant TCRVb CDR3 dominant peaks was observed post transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified post transplant. These results suggest that a chimeric TCR repertoire, comprising T cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis. This article is protected by copyright. All rights reserved

Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing

PURPOSE: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions. METHODS: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs. RESULTS: We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions. CONCLUSIONS: We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs

RANKL Cytokine: From Pioneer of the Osteoimmunology Era to Cure for a Rare Disease

Since its identification, the RANKL cytokine has been demonstrated to play a crucial role in bone homeostasis and lymphoid tissue organization. Genetic defects impairing its function lead to a peculiar form of autosomal recessive osteopetrosis (ARO), a rare genetic bone disease presenting early in life and characterized by increased bone density due to failure in bone resorption by the osteoclasts. Hematopoietic stem cell transplantation (HSCT) is the only option for the majority of patients affected by this life-threatening disease. However, the RANKL-dependent ARO does not gain any benefit from this approach, because the genetic defect is not intrinsic to the hematopoietic osteoclast lineage but rather to the mesenchymal one. Of note, we recently provided proof of concept of the efficacy of a pharmacological RANKL-based therapy to cure this form of the disease. Here we provide an overview of the diverse roles of RANKL in the bone and immune systems and review the clinical features of RANKL-deficient ARO patients and the results of our preclinical studies. We emphasize that these patients present a continuous worsening of the disease in the absence of a cure and strongly wish that the therapy we propose will be further developed

Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system