Reading tea leaves worldwide: decoupled drivers of initial litter decomposition mass-loss rate and stabilisation

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models

Delineating the deranged immune system in systemic lupus erythematosus and antiphospholipid syndrome

Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease that predominantly affects women of child-bearing age. In SLE, immune complexes are deposited into tissues, including skin, joint and kidneys, leading to tissue inflammation. The pathogenesis of SLE is complex and includes derailments of both the innate and adaptive immune system. Antiphospholipid antibodies (aPL) are strongly associated with thrombotic events and pregnancy morbidity among patients with SLE. Approximately 20% of SLE patients have antiphospholipid syndrome (APS), defined as the persistent presence of aPL in patients who experienced at least one thrombotic or obstetric complication. APS also affects patients without an underlying disease and is then termed primary APS (PAPS). In this thesis we investigated the role of the immune system in patients with APS as compared with patients with SLE. Key immunological abnormalities characteristic of SLE including the interferon (IFN) signature, release of neutrophil extracellular traps (NETs) and increased levels of B-cell activating factor (BAFF) were studied in patients with PAPS. We found that the IFN signature is present in 50% of PAPS patients as compared with 75% of SLE patients. In patients with APS, the IFN signature is associated with increases in cardiovascular disease associated non-classical monocyte subsets. Furthermore we identified that the IFN status of SLE and APS patients can be easily assessed by measuring galectin-9 levels in peripheral blood. Increases in NETs, low-density granulocytes (LDGs) and BAFF were found both in SLE and APS. In addition, mechanisms underlying increased activity of both plasmacytoid and myeloid dendritic cells (pDCs and mDCs) were studied in patients with SLE, SLE+APS and PAPS by means of RNA sequencing and microRNA profiling followed by subsequent in vitro studies. pDCs showed an overall reduced expression of microRNAs both in SLE and APS which was a result of the in vivo activation of pDCs by stimulation of Toll-like receptor 7. RNA sequencing identified a self-perpetuating role for type I IFN signalling in the activation of both pDCs and mDCs, both in SLE and APS. Such shared immunological perturbations among autoimmune diseases may relate to treatment responses of drugs targeting specific pathways. Hopefully, studying autoimmune diseases based on a molecular taxonomy, rather than classification criteria, improves treatment outcomes in patients with autoimmune diseases

Spatial patterns of plasmodium falciparum clinical incidence, asymptomatic parasite carriage and anopheles density in two villages in Mali

Heterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission. In the two study areas that were <1 km2 in size, we observed evidence for spatial clustering of Anopheles densities or malaria parasite carriage during the dry season. Anopheles density and malaria prevalence appeared associated in some of our detected hotspots. However, many households with high parasite prevalence or high Anopheles densities were located outside the identified hotspots. Our findings indicate that within small villages exposed to low- or mesoendemic-malaria transmission, spatial patterns in mosquito densities and parasite carriage are best detected in the dry season. Considering the high prevalence of parasite carriage outside detected hotspots, the suitability of the area for targeting control efforts to households or areas of more intense malaria transmission may be limited

Autoantibodies to Cytosolic 5 '-Nucleotidase 1A in Primary Sjogren's Syndrome and Systemic Lupus Erythematosus

Contains fulltext : 192050.pdf (publisher's version ) (Open Access

Submandibular gland amyloidosis: A rare manifestation of extranodal marginal lymphoma – A case report and literature review

Amyloidosis of the submandibular gland is a rare manifestation of extranodal marginal zone lymphoma (eMZL). Here, we present a case-report of a 62-year-old female patient with a history of eMZL, limited stage IIEA. The patient was initially treated with radiotherapy; however large glands remained with lack of clinical response to the radiotherapy. Consequently, a surgical excision of the submandibular glands was performed, and histology revealed massive amyloid deposits in the gland tissue next to eMZL. This case report highlights the importance of considering amyloidosis as a possible cause of submandibular gland enlargement in patients with a history of lymphoma and emphasizes the need for a histological diagnosis to direct appropriate treatment

The identification of CCL18 as biomarker of disease activity in localized scleroderma

Contains fulltext : 204252.pdf (publisher's version ) (Closed access)BACKGROUND: Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. OBJECTIVE: To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. METHODS: A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. RESULTS: From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs=0.4604, P<0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. CONCLUSION: CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease

Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk

Item does not contain fulltextOBJECTIVES: Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD. METHODS: A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA. RESULTS: The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with 'signature' markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction. CONCLUSION: CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5−CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies. Using high-dimensional protein and RNA single-cell analyses, Dutertre et al. analyze human dendritic cell and monocyte subsets and identify markers that delineate them and unravel their heterogeneity. They also reveal the presence of inflammatory CD14+ DC3s, a subset of cDC2s, that correlate with disease progression and may be functionally involved in systemic lupus erythematosus immunopathology. © 2019 Elsevier Inc

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5−CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies. Using high-dimensional protein and RNA single-cell analyses, Dutertre et al. analyze human dendritic cell and monocyte subsets and identify markers that delineate them and unravel their heterogeneity. They also reveal the presence of inflammatory CD14+ DC3s, a subset of cDC2s, that correlate with disease progression and may be functionally involved in systemic lupus erythematosus immunopathology. © 2019 Elsevier Inc