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Article ; Online: Systemic Lupus Erythematosus-related Lung Disease.

Bendstrup, Elisabeth / Lynn, Evelyn / Troldborg, Anne

Seminars in respiratory and critical care medicine

2024

Abstract: Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This ... ...

Abstract	Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0044-1782653
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Article: Systemic Lupus Erythematosus-related Lung Disease

Bendstrup, Elisabeth / Lynn, Evelyn / Troldborg, Anne

Seminars in Respiratory and Critical Care Medicine

(Pulmonary Complications of Connective Tissue Diseases)

2024

Series title	Pulmonary Complications of Connective Tissue Diseases
Abstract	Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.
Keywords	systemic lupus erythematosus ; acute lupus pneumonitis ; alveolar hemorrhage ; pleural effusion ; serositis ; shrinking lung syndrome ; interstitial lung disease ; pulmonary hypertension ; pulmonary embolism
Language	English
Publishing date	2024-03-28
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0044-1782653
Database	Thieme publisher's database

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Article ; Online: C3dg Quantification by PEG Precipitation and or TRIFMA.

Troldborg, Anne / Jensenius, Jens Christian

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2227, Page(s) 43–49

Abstract: Detection of complement activation products can be carried out in a number of ways, and different methods are used in different laboratories. No international standard for measuring complement activation in the clinical setting has been agreed upon.Here ... ...

Abstract	Detection of complement activation products can be carried out in a number of ways, and different methods are used in different laboratories. No international standard for measuring complement activation in the clinical setting has been agreed upon.Here we describe a modified assay for measuring C3dg. The assay is simple, inexpensive and stable. The estimation of C3dg directly reflects complement turnover independently of activation pathway.
MeSH term(s)	Animals ; Biomarkers/analysis ; Biomarkers/blood ; Blood Protein Electrophoresis ; Chemical Precipitation ; Complement Activation/physiology ; Complement C3b/analysis ; Complement C3b/isolation & purification ; Enzyme-Linked Immunosorbent Assay/methods ; Fluorescent Antibody Technique/methods ; Fluoroimmunoassay/methods ; Humans ; Immunoelectrophoresis/methods ; Inflammation/blood ; Inflammation/diagnosis ; Inflammation Mediators/analysis ; Inflammation Mediators/blood ; Peptide Fragments/analysis ; Peptide Fragments/isolation & purification ; Polyethylene Glycols/chemistry ; Rabbits
Chemical Substances	Biomarkers ; Inflammation Mediators ; Peptide Fragments ; complement C3d,g ; Polyethylene Glycol 6000 (30IQX730WE) ; Polyethylene Glycols (3WJQ0SDW1A) ; Complement C3b (80295-43-8)
Language	English
Publishing date	2021-04-13
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1016-9_4
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Article ; Online: Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) as a Compensatory Protease Inhibitor in Hereditary Angioedema (HAE).

Troldborg, Anne / Godnic-Polai, Zsofia / Cervenak, László / Hansen, Annette G / Farkas, Henriette / Thiel, Steffen

The Journal of allergy and clinical immunology

2024

Abstract: Background: Hereditary angioedema (HAE) is a genetic disorder that manifests as recurrent angioedema attacks, most frequently due to absent or reduced C1 inhibitor (C1-INH) activity. C1-INH is a crucial regulator of enzymatic cascades in the complement, ...

Abstract	Background: Hereditary angioedema (HAE) is a genetic disorder that manifests as recurrent angioedema attacks, most frequently due to absent or reduced C1 inhibitor (C1-INH) activity. C1-INH is a crucial regulator of enzymatic cascades in the complement, fibrinolytic, and contact systems. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is an abundant plasma protease inhibitor that can inhibit enzymes in the proteolytic pathways associated with HAE. Nothing is known about its role in HAE. Objective: Investigate ITIH4 activation in HAE, establish it as a potential biomarker, and explore its involvement in HAE-associated proteolytic pathways. Methods: Specific immunoassays for non-cleaved ITIH4 (Intact ITIH4) and an assay detecting both intact and cleaved ITIH4 (Total ITIH4) were developed. We initially tested serum samples from HAE patients (n=20), ACEI-induced edema patients (ACEI) (n=20), and unknown HAE patients (U-HAE) (n=20). Validation involved an extended cohort of 80 HAE patients (60 type I, 20 type II), including samples taken at attack and quiescent disease periods, as well as 100 healthy controls. Results: In 63% of HAE patients, the Intact ITIH4 assay showed lower signals than the Total ITIH4 assay. This difference was not observed in ACEI and U-HAE patients. Western blotting confirmed cleaved ITIH4 in low-Intact ITIH4 samples. In serum samples lacking intact endogenous ITIH4, we observed immediate cleavage of added recombinant ITIH4 suggesting continuous enzymatic activity in the serum. Confirmatory HAE cohort analysis revealed significantly lower intact ITIH4 levels in both HAE type 1 and type 2 patients compared to controls, with consistently low Intact/Total ITIH4 ratios during clinical HAE attacks. Conclusion: The disease-specific low intact ITIH4 levels highlight its unique nature in HAE. The results suggest that ITIH4 may exhibit compensatory mechanisms in HAE, suggesting its utility as a diagnostic and prognostic biomarker. The variations during quiescent and active disease periods raise intriguing questions about the dynamics of proteolytic pathways in HAE.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2024.03.028
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Article ; Online: Platelets and the Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus or Antiphospholipid Syndrome.

Vils, Signe Risbøl / Troldborg, Anne / Hvas, Anne-Mette / Thiel, Steffen

TH open : companion journal to thrombosis and haemostasis

2023 Volume 7, Issue 2, Page(s) e155–e167

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2023-06-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/a-2087-0314
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Article ; Online: The Status of Sanitation in Malawi: Is SDG6.2 Achievable?

Hinton, Rebekah G K / Macleod, Christopher J A / Troldborg, Mads / Kanjaye, Modesta B / Kalin, Robert M

International journal of environmental research and public health

2023 Volume 20, Issue 15

Abstract: Ensuring access to adequate and equitable sanitation and ending open defecation by 2030 is the focus of Sustainable Development Goal 6.2 (SDG6.2). We evaluated Malawi's progress towards SDG 6.2 (specifically the goal to end open defecation), presenting ... ...

Abstract	Ensuring access to adequate and equitable sanitation and ending open defecation by 2030 is the focus of Sustainable Development Goal 6.2 (SDG6.2). We evaluated Malawi's progress towards SDG 6.2 (specifically the goal to end open defecation), presenting the results of a national survey of over 200,000 sanitary facilities and evaluating their management. Based on non-linear population dynamics, we used a linear model to evaluate the reduction in open defecation between 1992-2018, and to project whether Malawi can meet the SDG target to end open defecation by 2030 under multiple scenarios of population growth. Whilst Malawi has made considerable progress in providing sanitary provision for the population, we estimate that, at the current rate of the provision of sanitary facilities, Malawi will not reach SDG 6.2 by 2030 under any of the modelled socioeconomic scenarios. Furthermore, we compare the estimates of the extent of sanitary provision classed as improved from multiple surveys, including the USAID Demographic and Health (DHS) Surveys and Government of Malawi Census data. We conclude that some of the surveys (particularly the 2015/16 DHS) may be overestimating the level of improved sanitary provision, and we hypothesize that this is due to how pit-latrines with earth/sand slabs are classed. Furthermore, we examine the long-term sustainability of pit-latrine use, investigating the challenge of pit-latrine abandonment and identifying pit-latrine filling as a cause of the abandonment in 30.2% of cases. We estimate that between 2020-2070, 31.8 (range 2.8 to 3320) million pit-latrines will be filled and abandoned, representing a major challenge for the safe management of abandoned latrines, a potential for long-term impacts on the groundwater quality, and a significant loss of investment in sanitary infrastructure. For Malawi to reach SDG 6.2, improvements are needed in both the quantity and quality of its sanitary facilities.
MeSH term(s)	Humans ; Sanitation/methods ; Malawi ; Groundwater ; Rural Population ; Toilet Facilities
Language	English
Publishing date	2023-08-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20156528
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Article: Platelets and the Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus or Antiphospholipid Syndrome

Vils, Signe Risbøl / Troldborg, Anne / Hvas, Anne-Mette / Thiel, Steffen

TH Open

2023 Volume 07, Issue 02, Page(s) e155–e167

Abstract: Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis even when they do not have antiphospholipid syndrome (APS). Interactions between complement activation and activated platelets have been suggested in SLE ... ...

Abstract	Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis even when they do not have antiphospholipid syndrome (APS). Interactions between complement activation and activated platelets have been suggested in SLE and APS and could play a role in the increased thrombosis risk. Objectives: To explore factors potentially related to the prothrombotic pathophysiology in patients with SLE, primary APS, and healthy controls, by investigating lectin pathway proteins (LPPs), complement activation, platelet aggregation, and platelet activation. Methods: This cross-sectional cohort study included 20 SLE patients, 17 primary APS, and 39 healthy controls. Flow cytometry and light transmission aggregometry were used to assess platelet activation and aggregation. Using time-resolved immunofluorometric assays, the plasma concentrations of 11 LPPs and C3dg, reflecting complement activation, were measured. Results: H-ficolin plasma concentrations were higher in SLE and APS patients than in controls ( p = 0.01 and p = 0.03). M-ficolin was lower in SLE than in APS ( p = 0.01) and controls ( p = 0.03). MAp19 was higher in APS patients than in SLE patients ( p = 0.01) and controls ( p < 0.001). In APS patients, MASP-2 and C3dg correlated negatively with platelet activation. Platelet-bound fibrinogen after agonist stimulation and C3dg concentrations correlated negatively with platelet activation. Conclusion: We observed significant differences between SLE and APS patients regarding complement proteins and platelet activation. Particularly the negative correlations between MASP-2 and C3dg with platelet activation only observed in APS patients suggest that interactions between complement activation and platelets differ in SLE and APS.
Keywords	platelets ; complement activation ; lectin ; systemic lupus erythematosus ; antiphospholipid syndrome
Language	English
Publishing date	2023-04-01
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/a-2087-0314
Database	Thieme publisher's database

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Article ; Online: Differentiating between activation via the lectin or the classical complement pathway in patients with systemic lupus erythematosus.

Larsen, Mads Lamm / Troldborg, Anne / Toonen, Erik J M / Hurler, Lisa / Prohaszka, Zoltan / Cervenak, László / Gudmann Hansen, Annette / Thiel, Steffen

Clinical and experimental immunology

2023 Volume 214, Issue 1, Page(s) 18–25

Abstract: Complement activation is a hallmark of systemic lupus erythematosus (SLE) and can proceed through the classical (CP), lectin (LP), or alternative pathway (AP). When managing SLE patients, pathway-specific complement activation is rarely monitored as ... ...

Abstract	Complement activation is a hallmark of systemic lupus erythematosus (SLE) and can proceed through the classical (CP), lectin (LP), or alternative pathway (AP). When managing SLE patients, pathway-specific complement activation is rarely monitored as clinical assays are unavailable. In this study, we aim to differentiate between CP- or LP-mediated complement activation in SLE patients by quantifying pathway-specific protein complexes, namely C1s/C1-inhibitor (C1-INH) (CP-specific activation) and MASP-1/C1-INH (LP-specific activation). Levels for both complexes were assessed in 156 SLE patients and 50 controls using two newly developed ELISAs. We investigated whether pathway-specific complement activation was associated with disease activity and lupus nephritis (LN). Disease activity stratification was performed using SLEDAI scores assessed at inclusion. C1s/C1-INH concentrations were significantly increased in active SLE patients (SLEDAI ≥6) when compared with SLE patients with low disease activity (SLEDAI <6, P < 0.01) and correlated with SLEDAI score (r = .29, P < 0.01). In active LN, MASP-1/C1-INH plasma concentrations were significantly increased compared with nonactive LN (P = 0.02). No differences in MASP-1/C1-INH plasma concentrations were observed between active SLE patients and patients with low disease activity (P = 0.11) nor did we observe a significant correlation with disease activity (r = 0.12, P = 0.15). Our data suggest that the CP and the LP are activated in SLE. The CP is activated in active SLE disease, whereas activation of the LP might be more specific to disease manifestations like LN. Our results warrant further research into specific complement pathway activation in SLE patients to potentially improve specific-targeted and tailored-treatment approaches.
MeSH term(s)	Humans ; Complement Pathway, Classical ; Lectins ; Mannose-Binding Protein-Associated Serine Proteases/metabolism ; Lupus Erythematosus, Systemic ; Complement Activation ; Lupus Nephritis/diagnosis
Chemical Substances	Lectins ; Mannose-Binding Protein-Associated Serine Proteases (EC 3.4.21.-)
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad070
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Article ; Online: Probabilistic modelling of the inherent field-level pesticide pollution risk in a small drinking water catchment using spatial Bayesian belief networks

M. Troldborg / Z. Gagkas / A. Vinten / A. Lilly / M. Glendell

Hydrology and Earth System Sciences, Vol 26, Pp 1261-

2022 Volume 1293

Abstract: Pesticides are contaminants of priority concern that continue to present a significant risk to drinking water quality. While pollution mitigation in catchment systems is considered a cost-effective alternative to costly drinking water treatment, the ... ...

Abstract	Pesticides are contaminants of priority concern that continue to present a significant risk to drinking water quality. While pollution mitigation in catchment systems is considered a cost-effective alternative to costly drinking water treatment, the effectiveness of pollution mitigation measures is uncertain and needs to be able to consider local biophysical, agronomic, and social aspects. We developed a probabilistic decision support tool (DST) based on spatial Bayesian belief networks (BBNs) that simulates inherent pesticide leaching risk to ground- and surface water quality to inform field-level pesticide mitigation strategies in a small (3.1 km 2 ) drinking water catchment with limited observational data. The DST accounts for the spatial heterogeneity in soil properties, topographic connectivity, and agronomic practices; the temporal variability of climatic and hydrological processes; and uncertainties related to pesticide properties and the effectiveness of management interventions. The rate of pesticide loss via overland flow and leaching to groundwater and the resulting risk of exceeding a regulatory threshold for drinking water was simulated for five active ingredients. Risk factors included climate and hydrology (e.g. temperature, rainfall, evapotranspiration, and overland and subsurface flow), soil properties (e.g. texture, organic matter content, and hydrological properties), topography (e.g. slope and distance to surface water/depth to groundwater), land cover and agronomic practices, and pesticide properties and usage. The effectiveness of mitigation measures such as the delayed timing of pesticide application; a 10 %, 25 %, or 50 % reduction in the application rate; field buffers; and the presence/absence of soil pan on risk reduction were evaluated. Sensitivity analysis identified the month of application, the land use, the presence of buffers, the field slope, and the distance as the most important risk factors, alongside several additional influential variables. The pesticide pollution risk from ...
Keywords	Technology ; T ; Environmental technology. Sanitary engineering ; TD1-1066 ; Geography. Anthropology. Recreation ; G ; Environmental sciences ; GE1-350
Subject code	910
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Copernicus Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Probabilistic modelling of the inherent field-level pesticide pollution risk in a small drinking water catchment using spatial Bayesian belief networks

Troldborg, Mads / Gagkas, Zisis / Vinten, Andy / Lilly, Allan / Glendell, Miriam

eISSN: 1607-7938

2022

Abstract	Pesticides are contaminants of priority concern that continue to present a significant risk to drinking water quality. While pollution mitigation in catchment systems is considered a cost-effective alternative to costly drinking water treatment, the effectiveness of pollution mitigation measures is uncertain and needs to be able to consider local biophysical, agronomic, and social aspects. We developed a probabilistic decision support tool (DST) based on spatial Bayesian belief networks (BBNs) that simulates inherent pesticide leaching risk to ground- and surface water quality to inform field-level pesticide mitigation strategies in a small (3.1 km 2 ) drinking water catchment with limited observational data. The DST accounts for the spatial heterogeneity in soil properties, topographic connectivity, and agronomic practices; the temporal variability of climatic and hydrological processes; and uncertainties related to pesticide properties and the effectiveness of management interventions. The rate of pesticide loss via overland flow and leaching to groundwater and the resulting risk of exceeding a regulatory threshold for drinking water was simulated for five active ingredients. Risk factors included climate and hydrology (e.g. temperature, rainfall, evapotranspiration, and overland and subsurface flow), soil properties (e.g. texture, organic matter content, and hydrological properties), topography (e.g. slope and distance to surface water/depth to groundwater), land cover and agronomic practices, and pesticide properties and usage. The effectiveness of mitigation measures such as the delayed timing of pesticide application; a 10 %, 25 %, or 50 % reduction in the application rate; field buffers; and the presence/absence of soil pan on risk reduction were evaluated. Sensitivity analysis identified the month of application, the land use, the presence of buffers, the field slope, and the distance as the most important risk factors, alongside several additional influential variables. The pesticide pollution risk from surface water runoff showed clear spatial variability across the study catchment, whereas the groundwater leaching risk was uniformly low, with the exception of prosulfocarb. Combined interventions of a 50 % reduced pesticide application rate, management of the plough pan, delayed application timing, and field buffer installation notably reduced the probability of a high risk of overland runoff and groundwater leaching, with individual measures having a smaller impact. The graphical nature of BBNs facilitated interactive model development and evaluation with stakeholders to build model credibility, while the ability to integrate diverse data sources allowed a dynamic field-scale assessment of “critical source areas” of pesticide pollution in time and space in a data-scarce catchment, with explicit representation of uncertainties.
Subject code	910
Language	English
Publishing date	2022-03-09
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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