Raum:
Posterbereich 4 - Foyer Ebene 1
Thema:
Inflammation, Infektion und Autoimmunerkrankungen
Präsentationsart:
Posterpräsentation
Dauer:
60 Minuten
08:00 Uhr
P-04-01:
A novel automated DiaSys procalcitonin immunoassay compared with four different BRAHMS-partnered immunoassays
A. Eidizadeh (Göttingen, DE)
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Autor:innen:
A. Eidizadeh (Göttingen, DE)
M. Wiederhold (Göttingen, DE)
M. Schnelle (Göttingen, DE)
A. Fischer (Göttingen, DE)
L. Binder (Göttingen, DE)
Introduction: Procalcitonin (PCT) is an important biomarker of sepsis and respiratory infections. Various automated immunoassays for measuring PCT in patient plasma are available in medical laboratories. However, due to a lack of international reference material for PCT, the assays are not always comparable.
Methods: In this study, we compared a new turbidimetric immunoassay from DiaSys, measured on the Abbott Architect c16000 and Alinity c, with four BRAHMS-associated chemiluminescence immunoassays (Abbott Architect i2000SR, Alinity i, Roche Cobas e411 and DiaSorin Liaison XL) using 120 random patient plasma samples from the clinical laboratory routine at the University Medical Center Goettingen.
Results: The DiaSys assay showed clear differences as compared to the BRAHMS-associated assays when measured on Architect c: i.e. 58% positive mean bias vs. Architect i, 67% vs. Cobas and 23% vs. Liaison. As a result, additional 19% our patients would have a suspected bacterial infection, when using PCT values from the DiaSys assay and commonly accepted decision limits. A crosscheck of the DiaSys calibrator on the BRAHMS-associated systems showed a low recovery of the calibrator material (approx. 50%).
Conclusions: Overall, this study shows significant differences between the DiaSys and BRAHMS-associated assays. This could be attributed to a potential DiaSys calibrator problem. This highlights the need for an international reference material for harmonization of the PCT assays.
08:05 Uhr
P-04-02:
Control of neutrophil effector function by the actin-regulatory protein Coronin-1a
N. Föger (Hannover, DE)
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Autor:innen:
A. Shaverskyi (Hannover, DE)
L. Kyeong-Hee (Hannover, DE)
N. Föger (Hannover, DE)
Background:
Neutrophils are innate immune cells that as key players of acute inflammation play fundamental roles in antimicrobial responses but can also contribute to inflammation-related tissue damage. To encounter pathogenic challenge, neutrophils have developed powerful defense mechanisms, such as the release of bioactive mediators from secretory granules and the generation of reactive oxygen species (ROS) to kill phagocytosed microbes. Neutrophil activation and execution of effector function involves dynamic reorganization of the actin cytoskeleton. The regulatory pathways and functional links between neutrophil activation/function and actin cytoskeletal regulation are, however, still only poorly understood.
Objective:
We here explored the role of the evolutionary highly conserved actin-regulatory protein Coronin-1a (Coro1a) for neutrophil effector function.
Methods:
Employing neutrophils from Coro1a-deficient and wild type mice we analyzed different neutrophil-mediated defense reactions that were induced by various stimuli. Additional experiments were aimed at uncovering the mechanism underlying Coronin-1a function in neutrophils.
Results:
Gene and protein expression analysis confirmed high expression of Coronin-1a in neutrophils. Analysis of developing neutrophil subsets in the bone marrow indicated normal neutrophil development in Coro1a-deficient mice and allowed us to examine the effects of Coro1a-deficiency on effector function of mature neutrophils. Consistent with a negative regulatory function of Coronin-1a on actin polymerization, Coro1a-deficient neutrophils had increased F-actin levels, indicating altered actin cytoskeletal organization. Importantly, evaluation of ROS generation (also called oxidative burst reaction), a key antimicrobial defense mechanisms of neutrophils, revealed impaired oxidative burst formation in Coro1a-deficient neutrophils in response to a wide range of different stimuli. Similarly, the release of prestored mediators from neutrophil granules, termed neutrophil degranulation, was also significantly reduced in Coro1a-deficient neutrophils, despite normal levels of intragranular compounds in resting cells. Initial mechanistic studies indicate an involvement of Coronin-1a in cellular signaling pathways during neutrophil activation.
Conclusion:
In summary, our data revealed alterations in actin cytoskeletal regulation in Coro1a-deficient neutrophils that were associated with impaired oxidative burst formation and decreased neutrophil degranulation (mediator release), thus indicating a critical involvement of Coronin-1a in neutrophil-mediated defense mechanisms. Ongoing experiments are aimed at further identifying the underlying mechanism and its physiological relevance.
08:10 Uhr
P-04-03:
2 years external quality assessment for the detection of anti-SARS-CoV-2 antibodies - a critical retrospective
M. Kittel (Mannheim, DE)
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Autor:innen:
M. Kittel (Mannheim, DE)
A. Bode (Bonn, DE)
R. Eichner (Mannheim, DE)
S. Aida (Mannheim, DE)
V. Ast (Mannheim, DE)
M. Neumaier (Mannheim, DE)
V. Haselmann (Mannheim, DE)
In the last year, a large number of assays for the serological detection of antibodies to the new SARS-CoV-2 virus have been brought to market and are being widely used in laboratories. These new developments have highlighted the importance of controlling the analytical methods currently in use to ensure patient safety. External quality assessment (EQA) is an important tool for both standardization of test results and their harmonization, and thus for ensuring high-quality diagnostic procedures. As these results are essential to estimate the prevalence of SARS-CoV-2 infections, the effect of immunizations, and post-infection immunity, this level of quality is mandatory. The Reference Institute for Bioanalytics (RfB) was the first provider to offer a proficiency test, for the detection of anti-SARS CoV-2 antibodies.
In the CoVimm EQA-schemes blinded panels of pre-characterized human serum samples with variable anti-SARS-CoV-2 antibody titers for detection of different anti-SARS-CoV-2-antibodies (IgG, IgA, IgM, total, nucleocapsid, and spike-protein-specific).
In this study, the 4 rounds of the CoVimm EQA were evaluated and compared in an aggregated format with the goal to gain insight into the quality and development of diagnostics for the detection of anti-SARS-CoV-2 antibodies.
In the four distribution rounds from 2020 to 2021, a total of 296 laboratories from 25 countries reported a total of 5,020 results for anti-SARS-CoV-2 antibody detection using more than 26 different assays. In terms of diagnostic sensitivity and specificity, significant differences were found between the various assays used and also between certified and lab-developed tests. Moreover, it could be observed that with the progress of the pandemic and the availability of vaccines, different requirements were imposed on the methods of antibody detection. The evaluation of the EQA-results also revealed, that there are still considerable deficits in the application of the test procedures on the part of the users. In particular, the use of obviously unsuitable assays concerning their intended use illustrates these application errors.
In summary, the EQA highlighted various aspects of the diagnostic situation. First, it should be emphasized that the testing landscape remains heterogeneous, but is increasingly concentrated among large providers.
Regrettably, there have been no noticeable improvements in the standardization of methods during the last year.
Assuming that the lessons learned from the current pandemic prove true, the number of cases, and thus the workload of laboratories will decrease significantly during the summer season. This break should be used urgently to refocus on and improve the quality of diagnostics offered. Current deficiencies should be addressed and laboratories should be aware of their responsibility for reported results.
08:15 Uhr
P-04-04:
The First Infection Wave: Clinical And Laboratory Characteristics Of COVID-19 Patients At The University Hospital Schleswig-Holstein In Kiel
V. Backes (Kiel, DE)
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Autor:innen:
V. Backes (Kiel, DE)
F. Leypoldt (Kiel, DE)
J. Franzenburg (Kiel, DE)
J. Dargvainiene (Kiel, DE)
D. Esser (Kiel, DE)
K. Wandinger (Kiel, DE)
R. Markewitz (Kiel, DE)
R. Junker (Kiel, DE)
Aims: After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan in December 2019, the novel virus spread quickly throughout the world, causing a pandemic. Although most people develop mild symptoms, especially old and multimorbid patients have an increased risk for an adverse outcome. The aim of this study was to analyse the cohort of coronavirus disease 2019 (COVID-19) patients at the University Hospital Schleswig-Holstein Campus Kiel during the first infection wave and derive a laboratory-value-based prediction model for severe COVID-19 in hospitalized patients.
Methods: This retrospective cohort study was conducted on 43 consecutive hospitalized patients with positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction, admitted to the University Hospital Schleswig-Holstein in Kiel from March to August 2020. Non-hospitalized patients were excluded. All patients were categorized according to the Ordinal Scale for Clinical Improvement (WHO) into two groups: mild to moderate disease versus severe disease. Clinical and laboratory parameters were acquired from patient files and compared between the groups.
Results: 31 patients were categorized as mild to moderate disease and 12 patients as severe disease. Age over 60 years (p=0.0479), chronical heart failure (p=0.0321) and oxygen supplementation at the day of admission (p < 0.0001) were associated with severe disease. Main complications of COVID-19 were acute renal failure, cardiac arrhythmia, and septic shock. 18.6 % of patients died during the evaluation period. Most common cause of death was septic shock. C-reactive protein (day 0+1 of hospitalisation: p=0.0007, day 4+5 of hospitalisation: p=0.0035), interleukine-6 (day 0+1: p=0.002, day 4+5: p < 0.0001), neutrophil-to-lymphocyte ratio (day 0+1: p=0.0002, day 4+5: p=0.0105) and procalcitonin concentrations (day 0+1: p=0.0002, day 4+5: p < 0.0001) were significantly higher in patients with severe disease. Furthermore, a low prothrombin time at the day of admission was associated with severe disease (p=0.0002). Sodium (day 0+1: p=0.1435, day 4+5: p=0.0006) and creatine kinase (day 0+1: p=0.0547, day 4+5: p < 0.0001) were significantly higher in patients with severe COVID-19 than in mild-to-moderate disease during the course of hospitalization but not at admission.
Conclusion: We could identify several inflammatory and acute-phase parameters which were significantly associated with a severe course of COVID-19 in hospitalized patients. Our results support the hypothesis that worse outcomes are mainly associated with hyperinflammation leading to multi-organ failure, including kidney damage and altered coagulation. A prediction model of risk factors for severe course of COVID-19 in hospitalized patients did not yield sufficient power due to the low incidence of COVID-19 in Schleswig-Holstein during the first wave resulting in small patient numbers.
08:20 Uhr
P-04-05:
Potential of integrative diagnostics predicting ICU demand in COVID-19 patients
C. Gerhards (Mannheim, DE)
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Autor:innen:
C. Gerhards (Mannheim, DE)
V. Haselmann (Mannheim, DE)
S. Schaible (Mannheim, DE)
V. Ast (Mannheim, DE)
M. Kittel (Mannheim, DE)
M. Ebert (Mannheim, DE)
A. Teufel (Mannheim, DE)
M. Thiel (Mannheim, DE)
A. Hertel (Mannheim, DE)
S. Schönberg (Mannheim, DE)
M. Frölich (Mannheim, DE)
M. Neumaier (Mannheim, DE)
Abstract
Introduction: The establishment of integrative diagnostic models combining quantitative imaging and laboratory findings may support the identification of vulnerable COVID-19 patients and aid assessments regarding required intensive care unit (ICU) treatment. We have investigated laboratory biomarkers including cell-free deoxyribonucleic acid (cfDNA) and radiomics for their synergistic integrated diagnostics potential.
Methods: Hospitalized SARS-CoV-2 infected patientes (n=52) were enrolled between May 2020 and September 2021. Retrospective image segmentation analyses of chest computed tomography (CT) and analysis of routine laboratory biomarkers together with prospectively obtained quantitative cfDNA concentrations were performed using separate feature selection and application of a minimal redundancy algorithm for both diagnostic modalities. The algorithm was established using cross-wise validation and subsequent verification in subset of algorithm-naïve patients. The clinical decision endpoint “ICU stay likely/unlikely” was optimized based on the prediction by the algorithm.
Results: The integrated model comprises six radiomics and seven laboratory biomarkers. Root mean square of the deviations between actual and predicted ICU-days was 5.3 days in cross-validation set and 12.3 days in test-cohort. Radiomic model accuracy was 0.54, cfDNA model accuracy was 0.47, routine laboratory model accuracy was 0.74 and combined model accuracy was 0.87 with an AUC of 0.91. The combined model performed superior to the individual radiological and laboratory models to predicting ICU requirement (adjusted R2 = 0.896).
Conclusion: The integration of radiomics and laboratory data shows synergistic potential to improve clinical decision making of COVID-19 patients. Based on the results of our routine patient cohort, this model may contribute to stratification of ICU capacities.
08:25 Uhr
P-04-06:
CD248 induces maladaptive unfolded protein response in diabetic kidney disease
R. Biemann (Leipzig, DE)
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Autor:innen:
R. Biemann (Leipzig, DE)
S. Krishnan (Magdeburg, DE)
J. Manoharan (Leipzig, DE)
D. Gupta (Leipzig, DE)
A. Mathew (Leipzig, DE)
S. Kohli (Leipzig, DE)
K. Shahzad (Leipzig, DE)
M. Naumann (Magdeburg, DE)
B. Isermann (Leipzig, DE)
Aims:
Dysfunction of mesangial cells plays a major role in the pathogenesis of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The underlying molecular mechanisms, however, are incompletely understood.
Methods and Results:
By unbiased gene expression analysis of glucose-exposed mesangial cells, we identified the transmembrane receptor CD248 as the most upregulated gene and maladaptive unfolded protein response (UPR) as one of the most upregulated pathways. Upregulation of CD248 was confirmed in glucose-stressed mesangial cells in vitro, in renal glomeruli isolated from diabetic mice (STZ and db/db models, representing type 1 and type 2 diabetes mellitus, respectively) in vivo, and in glomerular kidney sections from patients with DKD. Time course analysis revealed that glomerular CD248 induction precedes the onset of albuminuria, mesangial matrix expansion and maladaptive UPR activation (hallmarked by C/EBP homologous protein, CHOP, induction) but is paralleled by loss of the adaptive UPR regulator spliced X box binding protein (sXBP1). Mechanistically, CD248 induces the assembly of a multiprotein UPRosome comprising heat shock protein 90 (HSP90), BH3 interacting domain death agonist (BID) and inositol requiring enzyme 1 (IRE1α), in which BID impedes IRE1α-mediated XBP1 splicing and sXBP1-dependent gene expression. Overexpression of HSP90 or BID in vitro or genetic reduction of XBP1 in vivo abrogates the protective effects of CD248-deficiency.
Conclusion:
In the current study, we identified CD248 as a regulator of the adaptive UPR mediator XBP1 that induces maladaptive UPR signaling in renal glomeruli under diabetic conditions and in mesangial cells exposed to high glucose conditions in vitro. This research is expected to provide new mechanistic insights and identify the transmembrane receptor CD248 as a potential biomarker and a new druggable target in DKD.
08:30 Uhr
P-04-07:
Evaluation of a laboratory-based high-throughput SARS-CoV-2 antigen assay
S. Hörber (Tübingen, DE)
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Autor:innen:
S. Hörber (Tübingen, DE)
C. Drees (Tübingen, DE)
T. Ganzenmueller (Tübingen, DE)
D. Biskup (Tübingen, DE)
A. Peter (Tübingen, DE)
Objectives: Antigen tests are an essential part of SARS-CoV-2 testing strategies. Rapid antigen tests are easy to use but less sensitive compared to nucleic acid amplification tests (NAT) and less suitable for large-scale testing. In contrast, laboratory-based antigen tests are suitable for high-throughput immunoanalyzers. Here we evaluated the diagnostic performance of the laboratory-based Siemens Healthineers SARS-CoV-2 Antigen (CoV2Ag) assay.
Methods: In a public test center, from 447 individuals anterior nasal swab specimens as well as nasopharyngeal swab specimens were collected. The nasal swab specimens were collected in sample inactivation medium and measured using the CoV2Ag assay. The nasopharyngeal swab specimens were measured by RT-PCR. Additionally, 9046 swab specimens obtained for screening purposes in a tertiary care hospital were analyzed and positive CoV2Ag results confirmed by NAT.
Results: In total, 234/447 (52.3%) participants of the public test center were positive for SARS-CoV-2-RNA. Viral lineage B1.1.529 was dominant during the study. Sensitivity and specificity of the CoV2Ag assay were 88.5% (95%CI: 83.7%-91.9%) and 99.5% (97.4%-99.9%), respectively. Sensitivity increased to 93.7% (97.4%-99.9%) and 98.7% (97.4%-99.9%) for swab specimens with cycle threshold values < 30 and < 25, respectively. Out of 9046 CoV2Ag screening tests from hospitalized patients, 21 (0.2%) swab specimens were determined as false-positive by confirmatory NAT.
Conclusions: Using sample tubes containing inactivation medium the laboratory-based high-throughput CoV2Ag assay is a very specific and highly sensitive assay for detection of SARS-CoV-2 antigen in nasal swab specimens including the B1.1.529 variant. In low prevalence settings confirmation of positive CoV2Ag results by SARS-CoV-2-RNA testing is recommended.
08:35 Uhr
P-04-08:
Alternative polyadenylation regulates the SARS-CoV-2 entry factor NRP1
S. Hartleb (Mainz, DE)
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Autor:innen:
S. Hartleb (Mainz, DE)
E. Khan (Mainz, DE)
J. Nourse (Mainz, DE)
S. Danckwardt (Mainz, DE)
Background:
Neuropilin-1 (NRP1) has recently been identified as neuronal SARS-CoV-2 (co)receptor controlling host cell entry and infectivity. Apart from membrane bound NRP1 a truncated isoform lacking the transmembrane domain exists, which acts as functional antagonist to full-length NRP1. Recently, diversification of the transcriptome at the 3’end by alternative polyadenylation (APA) has emerged as a pervasive and evolutionarily conserved layer of gene regulation. APA is, for example, involved in the IgM heavy chain class switch in activated B-cells resulting in the conversion from a membrane bound to a soluble IgM. Here we set out to explore if and how APA affects the expression of soluble and membrane bound NRP1.
Methods:
The existence and location of several poly-A-sites in the human NRP1 gene was confirmed by 3' RACE PCR. To measure the influence of different APA factors on the expression of NRP1, we transfected BE2C cells with silencing RNAs to knockdown central components that regulate APA (PCF11, CPSF6 and NUDT21). The knockdown efficiency was controlled by western blot. The transfected cells were harvested to isolate RNA and proteins. RT-qPCR was performed to measure expression changes of NRP1 isoforms on mRNA level.
Results:
We confirmed different poly-A-site usage in the human NRP1 gene, which leads to the expression of different NRP1 RNA isoforms. We also demonstrate that CPSF6, a key determinant regulating APA, controls poly-A-site usage, with knockdown of CPSF6 resulting in upregulation of the soluble NRP1 isoform.
Conclusion:
We show that APA regulates the expression of NRP1, the neuronal SARS-CoV-2 entry (co)receptor. Downregulation of CPSF6 results in the expression of a truncated NRP1 mRNA isoform, encoding a soluble NRP1 protein that lacks the transmembrane domain. Truncated NRP1 thereby functionally competes with full-length membrane bound NRP1 and acts as a soluble decoy receptor. Based on these findings is tempting to speculate that APA evolved as a regulatory mechanism controlling SARS-CoV-2 cell entry and infectivity.
08:40 Uhr
P-04-09:
Performance evaluation of the EUROArray assay for molecular detection of dermatomycosis
M. Krolik (Buchs, CH)
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Autor:innen:
M. Krolik (Buchs, CH)
S. Bigler (Liebefeld, CH)
T. Bodmer (Liebefeld, CH)
M. Risch (Buchs, CH)
L. Risch (Buchs, CH)
N. Wohlwend (Buchs, CH)
Introduction
Superficial and cutaneous dermatomycosis is one of the most common fungal infection and remains a global concern. Increased mobility facilitates spreading and manifestation of originally rare dermatophyte species. While conventional culture is considered the gold standard for diagnosis of dermatomycosis, it is laborious, lengthy and requires a high level of expertise. In contrast, novel molecular approaches promise rapid yet sensitive and specific detection of dermatophytes. Here, we evaluate the performance of a novel PCR-based microarray compared to culture as reference.
Materials & Methods
A total of 272 KOH positive clinical samples were prospectively analysed in parallel by culture and the EUROArray Dermatomycosis (EUROImmun, Kriens, Switzerland). For cultural analysis, sample material was plated and incubated on Sabouraud, Dermatophyte and Candida Agar (BioMérieux, Petit-Lancy Switzerland). Primary material was digested by Proteinase K followed by automated extraction via easyMAG (BioMérieux, Petit-Lancy Switzerland) and subsequently used for the identification of 23 dermatophyte, 3 yeast and 3 mould species by the EUROArray.
Results
Dermathophytes were detected in 233/272 (85%) of the KOH positive clinical samples by EUROArray with Trichophyton rubrum (n=194) and Trichophyton interdigitale (n=36) clearly dominating over Microsporum canis (n=2) and Nannizzia gypsea (n=1). Whereas culturally only 93/272 (34%) of the obligate pathogenic agents could be identified. Results from culture were available after a mean of 25 days, while results from the EUROArray were obtained on the same day that the samples were processed.
Conclusion
Our data illustrate the increased sensitivity and shortened time to result compared to cultural analysis. We demonstrate that clinically relevant and human pathogenic dermatophytes, which did not yield a corresponding result in the time-consuming cultural rearing, are identified by molecular biological detection. Overgrowth by mould and inhomogeneous distribution of dermatophytes in the primary material are major obstacles. These can be overcome by the EUROArray enabling targeted therapy within a short period of time.
08:45 Uhr
P-04-10:
Sensitivity and Specificity of the Roche SARS-Cov-2 Antigen Assay in a hospital setting
B. Rolinski (Meißen, DE)
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Autor:innen:
B. Rolinski (Meißen, DE)
J. Gebauer (Meißen, DE)
A. Prantz (Meißen, DE)
D. Krnac (Meißen, DE)
C. Kutschker (Meißen, DE)
Aim
We evaluated the performance of the Roche SARS-CoV-2 Antigen Assay with respect to calibration stability and robustness as well as sensitivity and specificity.
Methods
We run the Roche SARS-CoV-2 Antigen Assay in three 400 bed hospitals on every patient at admission in conjunction with a SARS-CoV-2 rt-PCR (Seegene). Antigen tests were performed on two Cobas 6000 and one Elecsys e411. Data were evaluated from 10.3.2021 to 23.04.2022. A total of 35090 data sets were available for analysis.
Results
Antigen results ranged from 0,07 to 34149 U/ml and ct values ranged from 9 to 39,89. A total of 32642 samples were negative both by PCR and Antigen Assay, whereas 1421 samples where positive in both assay. 151 samples were false positive and 522 false negative resulting in a sensitivity of 0,7313 and a specificity of 0,9954.
Conclusion
The Roche SARS-CoV-2 Antigen assay performed very stable over more than one year and on three different instruments. The assay proved to be sufficient sensitive and highly specific for the detection of SARS-CoV-2 infection.
08:50 Uhr
P-04-12:
Antimicrobial Activity of CLEC3A: Potential in the Prevention and Treatment of Septic Arthritis
D. Elezagic (Köln, DE)
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Autor:in:
D. Elezagic (Köln, DE)
Introduction: The dramatic increase in antibiotic resistance has caused bacterial infections to once again become a serious global health threat. Moreover, the stagnating development of novel antibiotics urges for alternative antimicrobial agents. Particularly promising alternatives to conventional antibiotics are antimicrobial peptides (AMPs), which are part of the innate immune system. The cartilage-specific C-type lectin domain family 3 member A (CLEC3A) exhibits structural similarities to AMPs, which prompted us to investigate its antimicrobial activity.
Methods: We performed immunoblot to detect CLEC3A peptides in human cartilage extracts. To investigate their antimicrobial activity, we designed peptides and recombinantly expressed CLEC3A domains and used them to perform viable count assays using E.coli, P.aeruginosa and S.aureus. We investigated the mechanism of their antimicrobial activity by fluorescence and scanning electron microscopy. In addition, we coated CLEC3A peptides on titanium, a commonly used prosthetic material, and performed fluorescence microscopy to quantify bacterial adhesion. Moreover, we assessed the peptides' cytotoxicity against murine fibroblasts (NIH3T3) using MTT cell viability assays. To enhance the peptides´ performance, we altered the native peptides’ sequences, generating 6 modified peptides.
Results: CLEC3A fragments were indeed detected in human cartilage extracts. Moreover, bacterial supernatants lead to fragmentation of recombinant and cartilage-derived CLEC3A. CLEC3A-derived peptides killed E.coli, P.aeruginosa and S.aureus. The modified peptides exhibited even more efficient bacterial killing (including that of a Methicillin-resistant S.aureus strain). The antimicrobial activity of the native peptides occurs by permeabilizing bacterial membranes. Coating CLEC3A-derived AMPs on titanium lead to significantly reduced bacterial adhesion to the material. Additionally, modifying the peptides considerably reduces cytotoxicity levels against NIH3T3 cells.
Conclusions: We first identify cartilage-specific AMPs originating from CLEC3A and resolve the mechanism of their antimicrobial activity. In a translational approach, through modifying peptides´ sequences, we pinpoint CLEC3A-derived AMPs with enhanced antimicrobial activity and reduced cytotoxicity. In addition, by coating prosthetic material with the peptides, we point to a novel approach in the prevention and treatment of septic arthritis. In vivo experiments involving mouse infection models are currently ongoing and are expected to shed light on the practical use of native and modified CLEC3A-derived AMPs in fighting infection.