The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Arctic river organic carbon export through the ice-free season: isotopic and compositional analyses of DOM and POM collected in the Lena Delta between May and August 2014

Arctic rivers are known to export large quantities of carbon by discharge of dissolved and particulate organic matter, and in a warming and progressively moister Arctic, these exports may increase resulting in a reduction of continental carbon stocks in the region. In particular, mobilization of fossil carbon from terrestrial reservoirs, stored predominantly in Yedoma deposits, will result in a net carbon loss. Therefore, the radiocarbon (14C) contents of carbon exported via rivers are of great interest to understand the on-going processes. Recent work has shown that both particulate and dissolved organic matter exported by the Lena, one of the great rivers draining Siberian permafrost regions into the Laptev Sea, consists of a complex mixture of material derived from multiple sources (e.g., Winterfeld et al., 2015, Dubinenkov et al., 2014). Organic matter derived from the different sources likely differs in its reactivity once released from the frozen deposits into the river waters. For example, it has been shown that ancient carbon is very rapidly respired, leading to predominantly modern 14C signatures of dissolved organic carbon (DOC) in Arctic river waters discharged to the ocean (Mann et al., 2015). Arctic rivers are characterized by highly variable discharge rates with a pronounced maximum during the spring freshet associated with highest concentrations of DOC and particulate organic carbon (POC). Most studies investigating the isotopic composition and quality of carbon exported by Arctic rivers, however, rely on samples taken in summer during base flow, which is due to the logistical challenges associated with sampling in the remote Siberian permafrost regions. Here we present a record of δ13C and ∆14C of DOC and POC collected between late May during the freshet and late August 2014 in the Lena Delta, and compare them with δ13C and ∆14C of DOC and POC sampled in central Siberia. The latter represent the hinterland of the large rivers, while the Lena Delta data are considered to contain an integrated signal of the watershed. The central Siberian POC is generally younger than the Lena Delta POC in spring. Throughout spring and summer, POC becomes progressively older in central Siberia, while an initial trend towards older values in the spring samples from the Lena Delta is reversed in summer, associated with a shift towards more depleted δ13C values. We interpret these aging trends as reflecting progressive thawing throughout the ice-free season, resulting in mobilization of progressively older carbon from deeper thawed layers. The summer reversal indicates admixture of fresh organic matter. We furthermore analysed the biomarker composition of Lena Delta particulate organic matter collected in spring and summer. From spring to summer, we observe trends in abundance of individual leaf-wax derived biomarkers indicating higher abundance of algal biomass in the summer particles. Trends in biomarkers associated with soil microbes suggest a shift in sources through the ice-free season. Our data illustrate that considering the seasonal evolution of carbon discharge from Arctic rivers will be required to understand the underlying mechanisms and to predict future changes. Dubinenkov, I., R. Flerus, P. Schmitt-Kopplin, G. Kattner, B.P. Koch (2014): Origin-specific molecular signatures of dissolved organic matter in the Lena Delta. Biogeochemistry, doi: 10.1007/s10533-014-0049-0 Mann, P.J., T.I. Eglinton, C.P. McIntyre, N. Zimov, A. Davydova, J.E. Vonk, R.M. Holmes, R.G.M. Spencer (2015): Utilization of ancient permafrost carbon in headwaters of Arctic fluvial networks. Nature communications, doi: 10.1038/ncomms8856 Winterfeld, M., T. Laepple, G. Mollenhauer (2015): Characterization of particulate organic matter in the Lena River delta and adjacent nearshore zone, NE Siberia – Part I: Radiocarbon inventories. Biogeosciences, doi: 10.5194/bg-12-3769-201

Seasonal changes in particulate and dissolved organic matter composition and quality in the Lena River Delta

Arctic rivers are known to export large quantities of carbon by discharge of dissolved and particulate organic carbon (DOC, POC), and in a warming and progressively moister Arctic, these exports may increase resulting in a reduction of arctic continental carbon stocks. These rivers have highly variable discharge rates with a pronounced maximum during the spring freshet associated with highest concentrations of DOC and POC. Most studies investigating the isotopic composition and quality of carbon exported by Arctic rivers rely on samples taken in summer during base flow, which is due to the logistical challenges associated with sampling in the remote Arctic permafrost regions. Here we present a record of δ13C and ∆14C of DOC and POC collected between late May during the freshet and late August 2014 in the Lena River Delta. POC ∆14C shows an initial trend towards older values in the spring samples, which is reversed in summer, associated with a shift towards more depleted δ13C values. We interpret this aging trend as reflecting progressive thawing throughout the ice-free season, resulting in mobilization of progressively older carbon from deeper thawed layers. The summer reversal indicates admixture of aquatic organic matter. DOC ∆14C, in contrast, remains at relatively modern levels with rather constant δ13C values throughout the sampling period. We furthermore analysed the biomarker composition of Lena Delta particulate OM collected in spring and summer. From spring to summer, we observe trends in abundance of individual leaf-wax derived biomarkers indicating higher abundance of algal biomass in the summer particles. Trends in soil microbial biomarkers and compound-specific δD of leaf-wax lipids suggest a shift in sources towards higher contributions from the southern catchment in summer. DOC composition investigated with FT-ICR-MS changes from spring with higher abundances of compounds with high H/C and low O/C ratios to late summer, when fewer compounds were found. Our results illustrate the seasonal variability in composition and sources of organic matter discharged by the Lena River. Paired with the strong seassonality of the hydrograph, this implies that total annual discharge of organic matter contains a disproportionally high contribution from the northern part of the catchment

Comparison of nine different commercially available molecular assays for detection of SARS-CoV-2 RNA

To face the COVID-19 pandemic, the need for fast and reliable diagnostic assays for the detection of SARS-CoV-2 is immense. We describe our laboratory experiences evaluating nine commercially available real-time RT-PCR assays. We found that assays differed considerably in performance and validation before routine use is mandatory