Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity

Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF- B-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF- B signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity

Hematopoietic cell transplantation in severe combined immunodeficiency : The SCETIDE 2006-2014 European cohort

Publisher Copyright: © 2021 The AuthorsBackground: Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective: We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods: HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results: Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P 0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion: Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.Peer reviewe

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings

Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study.

peer reviewedAllogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT

Bi-temporal analysis of landscape changes in the easternmost mediterranean deltas using binary and classified change information

PubMedID: 23307139The aim of this study is (1) to quantify landscape changes in the easternmost Mediterranean deltas using bi-temporal binary change detection approach and (2) to analyze relationships between conservation/management designations and various categories of change that indicate type, degree and severity of human impact. For this purpose, image differencing and ratioing were applied to Landsat TM images of 1984 and 2006. A total of 136 candidate change images including normalized difference vegetation index (NDVI) and principal component analysis (PCA) difference images were tested to understand performance of bi-temporal pre-classification analysis procedures in the Mediterranean delta ecosystems. Results showed that visible image algebra provided high accuracies than did NDVI and PCA differencing. On the other hand, Band 5 differencing had one of the lowest change detection performances. Seven superclasses of change were identified using from/to change categories between the earlier and later dates. These classes were used to understand spatial character of anthropogenic impacts in the study area and derive qualitative and quantitative change information within and outside of the conservation/ management areas. Change analysis indicated that natural site and wildlife reserve designations fell short of protecting sand dunes from agricultural expansion in the west. East of the study area, however, was exposed to least human impact owing to the fact that nature conservation status kept human interference at a minimum. Implications of these changes were discussed and solutions were proposed to deal with management problems leading to environmental change. © 2013 Springer Science+Business Media New York

Analysis of road development and associated agricultural land use change

PubMedID: 29209817Development of road network is one of the strongest drivers of habitat fragmentation. It interferes with ecological processes that are based on material and energy flows between landscape patches. Therefore, changes in temporal patterns of roads may be regarded as important landscape-level environmental indicators. The aim of this study is to analyze road development and associated agricultural land use change near the town of Erdemli located in the eastern Mediterranean coast of Turkey. The study area has witnessed an unprecedented development of agriculture since the 2000s. This process has resulted with the expansion of the road network. Associations between agricultural expansion and road development were investigated. High-resolution satellite images of 2004 and 2015 were used to analyze spatial and temporal dimensions of change. Satellite images were classified using a binary approach, in which land areas were labeled as either “agriculture” or “non-agriculture.” Road networks were digitized manually. The study area was divided into 23 sublandscapes using a regular grid with 1-km cell spacing. Percentage of landscape (PL) for agriculture and road density (RD) metrics were calculated for the earlier (2004) and later (2015) years. Metric calculations were performed separately for each of the 23 sublandscapes in order to understand spatial diversity of agriculture and road density. Study results showed that both RD and PL exhibited similar increasing trends between 2004 and 2015. © 2017, Springer International Publishing AG, part of Springer Nature.CAYDAG 111Y253Funding information This project is supported by Turkish Scientific and Technological Research Council (TUBITAK) under the Grant Number CAYDAG 111Y253

Land-use change and urbanization of Adana, Turkey

This study analyses land-use/land-cover (LULC) changes in Adana city, Turkey, using satellite data of 1984 and 2000. Study of the expansion of the city over adjacent agricultural fields and semi-natural areas was the major focus. The satellite images were classified using supervised classification prior to comparison of LULC on two different dates. The change map was produced by pixel-to-pixel comparison of the classified images. Urban and built-up area increased by a factor of 2.07 during the 16 years; about 30 per cent on agricultural land and 70 per cent on previously semi-natural land. Permanent immigration and urban development strategies were the main driving forces. Some policy perspectives are also given. Copyright © 2003 John Wiley and Sons, Ltd

Analysis of landscape changes as a tool for monitoring ecosystem dynamics [Ekosistem dinamiklerinin i·zlenmesine bir araç olarak peyzaj degişimlerinin analizi]

This study aimed to provide a framework as a basis for determining qualitative and quantitative aspects of landscape changes. Special emphasis was placed on pixel-based comparison of satellite images and the advantages of this approach over traditional change detection based on a simple comparison of the area of a given land cover type at different dates was discussed. The results of this study showed that coastal landscape has high spatial heterogeneity. The results also suggested that rapid and complex changes in these areas resulting from human interference can be identified accurately by using spatially-referenced information. The use of "from one date to another" (-from ,-to) change categories was reported to provide more information on the movement, fragmentation, and consolidation components of landscape changes and the utility of the products of this approach for creating future secenarios was mentioned