Article
Biochemistry & Molecular Biology
Aleksandra Kaluzna, Agnieszka Jura-Poltorak, Alicja Derkacz, Krystyna Olczyk, Katarzyna Komosinska-Vassev
Summary: This case-control study aimed to identify novel biomarkers for Crohn's disease (CD) and found significant differences in serum concentrations of proguanylin (pro-GN), pentraxin 3 (PTX3), and S100A12 between CD patients and healthy individuals. The serum profile of PTX3 was also correlated with disease activity and treatment response. These findings suggest that measuring pro-GN, PTX3, and S100A12 could be beneficial for the diagnosis and monitoring of CD.
Article
Rheumatology
Jean-Paul Makhzoum, Peter C. Grayson, Cristina Ponte, Joanna Robson, Ravi Suppiah, Richard A. Watts, Raashid Luqmani, Peter A. Merkel, Christian Pagnoux
Summary: This study describes the spectrum and initial impact of pulmonary manifestations in primary systemic vasculitides. Pulmonary manifestations were observed in all types of vasculitides, with eosinophilic GPA, microscopic polyangiitis, and granulomatosis with polyangiitis being the most common. Pulmonary manifestations were more severe and associated with permanent damage in ANCA-associated vasculitis.
Article
Immunology
Kristen M. Gibson, Renate Kain, Raashid A. Luqmani, Colin J. Ross, David A. Cabral, Kelly L. Brown
Summary: A study found that 35% of children with chronic systemic vasculitis had moderate to high LAMP-2-ANCA titers, with 20% having high positive titers. LAMP-2-ANCA titers did not correlate with classic ANCA titers or disease activity at diagnosis, but were negatively correlated with changes in GFR at 12-month follow-up.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Dhruti P. Chen, Claudia P. Aiello, DeMoris McCoy, Taylor Stamey, Jiajin Yang, Susan L. Hogan, Yichun Hu, Vimal K. Derebail, Eveline Y. Wu, J. Charles Jennette, Ronald J. Falk, Dominic J. Ciavatta
Summary: A GWAS identified an association between PR3-ANCA and a SNP (rs62132293) upstream of the PRTN3 gene. The variant (G allele) was shown to be an expression quantitative trait locus in healthy controls, but its clinical impact is still unknown. Patients carrying the variant allele had elevated leukocyte PRTN3 expression compared to non-carriers, while healthy controls had low PRTN3 regardless of genotype.
Article
Immunology
Marcin Surmiak, Katarzyna Wawrzycka-Adamczyk, Joanna Kosalka-Wegiel, Stanisnaw Polanski, Marek Sanak
Summary: This study characterized the profile of microRNAs trafficked by extracellular vesicles (EVs) in patients with granulomatosis with polyangiitis (GPA). Four differentially expressed microRNAs were identified in EVs from GPA patients, with miR-223-3p being the best discriminator between GPA patients and healthy controls. MiR-664a-3p was able to discriminate between active and remission phases of GPA. The correct classification rate based on multivariate discriminant analysis was 92% for acute phase and 85% for all study participants. Pathway analysis revealed potential target genes of these microRNAs, involved in focal adhesion, mTOR signaling, and neutrophil extracellular traps formation. Two microRNAs positively correlated with disease activity were found to be involved in neutrophil extracellular traps formation and apoptosis inhibition.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Su Duy Nguyen, Katariina Maaninka, Mikko Mayranpaa, Marc Baumann, Rabah Soliymani, Miriam Lee-Rueckert, Matti Jauhiainen, Petri T. Kovanen, Katariina Oorni
Summary: This study demonstrates the presence of PR3 in human atherosclerotic lesions and its ability to modify the structure and functions of LDL and HDL particles, contributing to the lipid-driven component of atherogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Medical Laboratory Technology
Taejun Yoon, Lucy Eunju Lee, Sung Soo Ahn, Jung Yoon Pyo, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee
Summary: This study found that serum progranulin is closely associated with disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and higher levels of serum progranulin may indicate higher risk of AAV disease activity.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Article
Multidisciplinary Sciences
Spyridon Lipka, Lennard Ostendorf, Udo Schneider, Falk Hiepe, Falko Apel, Tobias Alexander
Summary: This study aimed to investigate the contributions of neutrophils and NETs to the pathogenesis of GPA. The results showed that GPA patients had increased levels of activated and immature LDGs, and their sera degraded NETs less effectively, which weakly correlated with markers of disease activity.
Review
Medicine, General & Internal
Jason M. Springer, Kevin Byram
Summary: Polyarteritis nodosa is a form of vasculitis characterized by inflammation of medium-sized arteries. The discovery of additional causes and changing nomenclature have led to a decline in its incidence. Common manifestations include constitutional symptoms, skin involvement, peripheral neuropathy, gastrointestinal disease, and renal involvement. DADA2 is an important genetic cause to distinguish from primary PAN, as treatment with TNF inhibitors can prevent morbidity and mortality. The prognosis has greatly improved with systemic immunosuppressive therapy, with a 5-year survival rate above 80%.
POSTGRADUATE MEDICINE
(2023)
Article
Medicine, General & Internal
Desiree Tampe, Peter Korsten, Philipp Stroebel, Samy Hakroush, Bjoern Tampe
Summary: Proteinuria in ANCA GN is correlated with distinct clinicopathological characteristics, such as MPO subtype, MPA diagnosis, and severe kidney function deterioration. The presence of proteinuria is most prominent in ANCA GN with sclerotic class and high ANCA renal risk score, indicating specific renal involvement rather than systemic disease activity.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Eric K. Patterson, Carolina Gillio-Meina, Claudio M. Martin, Douglas D. Fraser, Logan R. Van Nynatten, Marat Slessarev, Gediminas Cepinskas
Summary: Both PR3 and HLE, serine proteases abundant in PMNs, contribute independently to vascular dysfunction in sepsis. Exogenous application of PR3 or HLE increases HUVEC permeability and decreases electrical resistance, effects that can be mitigated by CORM-3 treatment.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Maaike Cockx, Marfa Blanter, Mieke Gouwy, Pieter Ruytinx, Sara Abouelasrar Salama, Sofie Knoops, Noemie Poertner, Lotte Vanbrabant, Natalie Lorent, Mieke Boon, Sofie Struyf
Summary: Investigations on patients with primary ciliary dyskinesia (PCD) revealed that neutrophils in their peripheral blood produce fewer reactive oxygen species upon stimulation with bacterial products or cytokines, and show reduced capacity in releasing DNA during neutrophil extracellular trap formation. These findings suggest that the reduced neutrophil activity in PCD patients may contribute to recurrent respiratory infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Jerome Granel, Brice Korkmaz, Dalila Nouar, Stefanie A. I. Weiss, Dieter E. Jenne, Roxane Lemoine, Cyrille Hoarau
Summary: Granulomatosis with polyangiitis is a rare and serious necrotizing auto-immune vasculitis associated with PR3-ANCA. Despite current therapies, GPA remains a serious disease with high mortality and relapse risk, highlighting the need for new biomarkers and therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medical Laboratory Technology
Lucy Eunju Lee, Jung Yoon Pyo, Sung Soo Ahn, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee
Summary: The fibrinogen to albumin ratio at diagnosis could reflect the cross-sectional Birmingham vasculitis activity score (BVAS) in patients with AAV, but it was not predictive of poor outcomes during follow-up.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Article
Pediatrics
Begum Avci, Tuba Kurt, Fatma Aydin, Elif Celikel, Zahide Ekinci Tekin, Muge Sezer, Nilufer Tekgoz, Cuneyt Karagol, Serkan Coskun, Melike Mehves Kaplan, Umut Selda Bayrakci, Banu Acar
Summary: The aim of this study was to identify IgAVN-associated factors and evaluate the usability of PVAS at diagnosis as an early marker for the development of IgAVN. The results showed that PVAS > 3 at diagnosis is an independent predictor of IgAVN and low serum albumin is an independent risk factor for IgAVN.
PEDIATRIC NEPHROLOGY
(2023)
Article
Rheumatology
Ruud H. J. Verstegen, Peter Shrader, Stephen J. Balevic, Timothy Beukelman, Colleen Correll, Anne Dennos, Thomas Phillips, Brian M. Feldman
Summary: This study aimed to determine the dose-response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). The results did not confirm the hypothesis that increased dosing of TNF inhibitors leads to improved treatment outcomes.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Kiem Oen, Karine Toupin-April, Brian M. Feldman, Roberta A. Berard, Cia'ran M. Duffy, Lori B. Tucker, Jiahao Tian, Dax G. Rumsey, Jaime Guzman
Summary: This study validates the JIA parent global assessment as a valid measure of health-related quality of life. Comparisons with other HRQoL measures show good construct validity. However, reliability estimates and measurement errors were unsatisfactory, likely due to the time interval between assessments. Causal pathway analysis confirms previous findings.
Article
Rheumatology
Jonathan Park, Michelle Batthish, Roberta A. Berard, Gaelle Chedeville, Jean-Philippe Proulx-Gauthier, Dax G. Rumsey, Lori B. Tucker, Stephanie Wong, Jaime Guzman
Summary: Canadian pediatric rheumatology practices were generally in line with the 2019 JIA guideline recommendations, except for the frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis.
Article
Ecology
Christina L. Wiesmann, Yue Zhang, Morgan Alford, Corri D. Hamilton, Manisha Dosanjh, David Thoms, Melanie Dostert, Andrew Wilson, Daniel Pletzer, Robert E. W. Hancock, Cara H. Haney
Summary: Members of the bacterial genus Pseudomonas can form mutualistic, commensal, and pathogenic associations with diverse hosts. The study found that the regulatory gene ColR/S is functionally conserved between Pseudomonas aeruginosa and Pseudomonas fluorescens, but there are differences in the regulon. ColR/S allows Pseudomonas to sense and respond to a host, and the divergence of the ColR regulon may be related to different lifestyles.
Article
Pediatrics
Khalid Taha, Atul Sharma, Kristine Kroeker, Colin Ross, Bruce Carleton, David Wishart, Mara Medeiros, Tom D. D. Blydt-Hansen
Summary: This study aims to develop a novel urine test based on metabolomics to estimate the exposure of mycophenolate in pediatric renal transplantation. The urine samples were analyzed for 133 unique metabolites, and a top 10 urinary metabolite classifier was developed to estimate MPA exposure. The test was validated and showed correlation with allograft inflammation and eGFR ratio.
PEDIATRIC TRANSPLANTATION
(2023)
Article
Rheumatology
Kristen I. Gibson, Britt Drogemoller, Dirk M. Foell, Susanne Benseler, Jinko Graham, Robert E. W. A. Hancock, Raashid A. Luqmani, David L. Cabral, Kelly J. Brown, Colin Ross
Summary: This study conducted a genome-wide association study of pediatric ANCA-associated vasculitis (AAV) and found a significant genetic association between HLA-DPB1*04:01 allele and pediatric AAV. The study also suggested that childhood- and adult-onset vasculitis may share a common genetic predisposition. These findings contribute to improved classification tools and treatment strategies for AAV.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Si-Yue Yu, Tiffany Carlaw, Tyler Thomson, Alexandra Birkenshaw, Genc Basha, Daniel Kurek, Cassie Huang, Jayesh Kulkarni, Lin-Hua Zhang, Colin J. D. Ross
Summary: The development of CRISPR genome editing technology has potential for treating genetic diseases, but delivering genome editors to affected tissues is challenging. In this study, a luminescent ABE (LumA) mouse model was developed, which showed restoration of luciferase activity through A-to-G correction. The model was validated using FDA-approved lipid nanoparticle formulations and demonstrated successful restoration of luciferase activity in treated mice. This model can be used to evaluate the efficacy and safety of genome editors and delivery systems for optimizing genome editing therapeutics.
Review
Economics
Gillian R. Currie, Brittany Gerber, Diane Lorenzetti, Karen MacDonald, Susanne M. Benseler, Francois P. Bernier, Kym M. Boycott, K. Vanessa Carias, Bettina Hamelin, Robin Z. Hayeems, Claire LeBlanc, Marinka Twilt, Gijs van Rooijen, Durhane Wong-Rieger, Rae S. M. Yeung, Deborah A. Marshall
Summary: Rare diseases impose a significant burden on various aspects. Limited evidence exists on the socioeconomic burden of rare diseases, particularly for those without available treatments. This study developed a framework to guide future research on the cost elements of rare diseases.
Article
Multidisciplinary Sciences
Shahid Chaudhary, Zahir Ali, Muhammad Tehseen, Evan F. Haney, Aaron Pantoja-Angles, Salwa Alshehri, Tiannyu Wang, Gerard J. Clancy, Maya Ayach, Charlotte Hauser, Pei-Ying Hong, Samir M. Hamdan, Robert E. W. Hancock, Magdy Mahfouz
Summary: This study demonstrates the efficient production of bioactive amidated AMPs through transient expression in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine alpha-amidating mono-oxygenase. The AMPs purified from plants exhibit robust killing activity against highly virulent and antibiotic-resistant pathogens, and can prevent their biofilm formation when used in combination with antibiotics. The techno-economic analysis also shows the potential economic advantages and scalability for industrial use of this platform.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Arjun S. Baghela, Jasmine Tam, Travis M. Blimkie, Bhavjinder K. Dhillon, Robert E. W. Hancock
Summary: In this study, a compendium of 103 gene sets related to sepsis was built by collecting data from transcriptomic studies. The gene sets comprise 20,899 unique genes, and the study describes the commonly involved molecular mechanisms. A database called SeptiSearch was created to provide bioinformatic tools for the sepsis community to explore and validate these gene sets.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
Summary: This study compared the gene expression trajectories between severe COVID-19 patients and contemporaneous non-COVID-19 severe sepsis patients during hospitalization. COVID-19 patients had 1,215 differentially expressed genes compared to non-COVID-19 sepsis patients at ICU admission, but the number dropped to 9 genes after one week. The findings highlight the importance of early antiviral treatment for COVID-19 and the potential for heme-related therapeutics.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Cesar de la Fuente-Nunez, Angela Cesaro, Robert E. W. Hancock
Summary: Despite advances in antibiotic discovery, millions of people still die from infections every year. Antibiotic failure is not solely due to antibiotic resistance, but also related to biofilm formation, sepsis, and the microbiome. To address the crisis of antibiotic failure, it is necessary to explore treatment strategies beyond antibiotics and develop new anti-infectives or host-directed therapies.
DRUG RESISTANCE UPDATES
(2023)
Article
Dentistry, Oral Surgery & Medicine
Jinghao Hu, Jian Yu, He Liu, Zhejun Wang, Markus Haapasalo, Evan F. Haney, Robert E. W. Hancock, Shuli Deng, Ya Shen
Summary: This study evaluated the antimicrobial effects of commercially available mouthrinses and a D-enantiomeric peptide on oral multispecies biofilms. The results showed that DJK-5 demonstrated the highest percentage of dead bacteria and may be a potential candidate for future mouthrinses.
JOURNAL OF DENTISTRY
(2023)
Article
Immunology
Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
Summary: Transcriptional evidence showed persistent immune dysfunction in both severe COVID-19 and non-COVID-19 septic patients, associated with increased mortality. This highlights the potential for immunomodulatory therapies targeting common mechanisms of immune dysfunction in both diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Dan Wang, Jian Yu, He Liu, Tian Zhang, Evan F. Haney, Robert E. W. Hancock, Lin Peng, Ya Shen
Summary: This study aimed to investigate the effectiveness of DJK-5-D enantiomeric antibiofilm peptide on the corrosion resistance of titanium with different surface roughness. The results showed that DJK-5 effectively enhanced the corrosion resistance of titanium while killing S. mutans biofilms, with smooth surfaces more susceptible to peptide treatment.
JOURNAL OF DENTISTRY
(2023)