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RMD Open Jun 2024The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive...
OBJECTIVES
The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.
METHODS
Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models.
RESULTS
Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001).
CONCLUSIONS
The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Male; Female; Child; Adolescent; Peroxidase; Myeloblastin; Retrospective Studies; Kidney Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Child, Preschool; Prognosis; Predictive Value of Tests
PubMed: 38886004
DOI: 10.1136/rmdopen-2024-004315 -
JCI Insight Jun 2024Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several...
Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several factors, including reactive CD4+ T cell proliferation, and further provides no specificity information. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissuelocalized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.
PubMed: 38885329
DOI: 10.1172/jci.insight.174168 -
Journal of Pregnancy 2024There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant... (Comparative Study)
Comparative Study
Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.
There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant ( = 1.248, > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Di antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Di should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.
Topics: Humans; Female; Pregnancy; Erythrocytes; China; Adult; Pregnancy, Multiple; Isoantibodies; Rho(D) Immune Globulin; Sensitivity and Specificity; Antibody Specificity; MNSs Blood-Group System; Asian People; Kidd Blood-Group System; East Asian People
PubMed: 38883212
DOI: 10.1155/2024/5539776 -
Frontiers in Cellular and Infection... 2024As a contagious and chronic disease in the livestock industry, Paratuberculosis is a significant threat to dairy herds' genetic and economic resources. Due to intensive...
INTRODUCTION
As a contagious and chronic disease in the livestock industry, Paratuberculosis is a significant threat to dairy herds' genetic and economic resources. Due to intensive breeding and high production of dairy cattle, the incidence and prevalence are higher. Developing non-destructive diagnostic methods for the early detection and identification of healthy animals is paramount for breeding programs. Conventional methods are almost entirely destructive, have low accuracy, lack precision, and are time-consuming. Near-infrared spectroscopy (NIRS) and aquaphotomics can detect changes in biofluids and thus have the potential to diagnose disease. This study aimed to investigate the diagnostic ability of NIRS and aquaphotomics for Paratuberculosis in dairy cattle.
METHODS
Blood plasma from dairy cattle was collected in the NIR range (1,300 nm to 1,600 nm) 60 days before and 100 days to 200 days after calving in two groups, positive and negative, using the same consecutive enzyme-linked immunosorbent assay test results three times as a reference test.
RESULTS
NIRS and aquaphotomics methods invite 100% accuracy, sensitivity, and specificity to detect Paratuberculosis using data mining by unsupervised method, Principal Component Analysis, and supervised methods: Soft Independent Modeling of Class Analogiest, Linear Discriminant Analysis, Quadratic Discriminant Analysis, Partial Least Square-Discriminant Analysis, and Support Vector Machine models.
DISCUSSION
The current study found that monitoring blood plasma with NIR spectra provides an opportunity to analyze antibody levels indirectly via changes in water spectral patterns caused by complex physiological changes, such as the amount of antibodies related to Paratuberculosis by aquagram.
Topics: Animals; Cattle; Paratuberculosis; Spectroscopy, Near-Infrared; Cattle Diseases; Sensitivity and Specificity; Mycobacterium avium subsp. paratuberculosis; Female; Dairying; Enzyme-Linked Immunosorbent Assay
PubMed: 38873096
DOI: 10.3389/fcimb.2024.1374560 -
Pathology, Research and Practice Jun 2024Expression and function of TRPC3 and TRPC6 in the pancreas is a controversial topic. Investigation in human tissue is seldom. We aimed to provide here a detailed...
BACKGROUND
Expression and function of TRPC3 and TRPC6 in the pancreas is a controversial topic. Investigation in human tissue is seldom. We aimed to provide here a detailed description of the distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas.
METHODS
We collected healthy samples from cadavers (n = 4) and visceral surgery (n = 4) to investigate the respective expression profiles using immunohistochemical tracing with knockout-validated antibodies.
RESULTS
TRPC3- and TRPC6-proteins were detected in different pancreatic structures including acinar cells, as well as epithelial ductal cells from intercalate, intralobular, and interlobular ducts. Respective connective tissue layers appeared unstained. Endocrine islets of Langerhans were clearly and homogenously immunolabeled by the anti-TRPC3 and anti-TRPC6 antibodies. Insular α, β, γ, and δ cells were conclusively stained, although no secure differentiation of cell types was performed.
CONCLUSIONS
Due to aforementioned antibody specificity verification, protein expression in the immunolabeled localizations can be accepted. Our study in human tissue supports previous investigations especially with respect to acinar and insular α and β cells, while other localizations are here reported for the first time to express TRPC3 and TRPC6, ultimately warranting further research.
PubMed: 38870712
DOI: 10.1016/j.prp.2024.155403 -
Pulmonary Circulation Apr 2024A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study...
A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA-based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RHC). The CIPHER-MRI study was added to assess the performance of this CIPHER signature in a population with low probability of having PH who underwent cardiac magnetic resonance imaging (cMRI) instead of RHC. The microRNA signature was developed using a penalized linear regression (LASSO) model. Data were modeled both with and without N-terminal pro-brain natriuretic peptide (NT-proBNP). Signature performance was assessed against predefined thresholds (lower 98.7% CI bound of ≥0.73 for sensitivity and ≥0.53 for specificity, based on a meta-analysis of echocardiographic data), using RHC as the true diagnosis. Overall, 926 CIPHER participants were screened and 888 were included in the analysis. Of 688 RHC-confirmed PH cases, approximately 40% were already receiving PH treatment. Fifty microRNA (from 311 investigated) were algorithmically selected to be included in the signature. Sensitivity [97.5% CI] of the signature was 0.85 [0.80-0.89] for microRNA-alone and 0.90 [0.86-0.93] for microRNA+NT-proBNP, and the corresponding specificities were 0.33 [0.24-0.44] and 0.28 [0.20-0.39]. Of 80 CIPHER-MRI participants with evaluable data, 7 were considered PH-positive by cMRI whereas 52 were considered PH-positive by the microRNA signature. Due to low specificity, the CIPHER miRNA-based signature for PH (either with or without NT-proBNP in model) did not meet the prespecified diagnostic threshold for the primary analysis.
PubMed: 38868397
DOI: 10.1002/pul2.12386 -
Access Microbiology 2024Leptospirosis is a zoonotic disease that is prevalent worldwide. Leptospiral 3-hydroxyacyl-CoA dehydrogenase (3-HADH) is excreted in the urine of infected individuals....
Leptospirosis is a zoonotic disease that is prevalent worldwide. Leptospiral 3-hydroxyacyl-CoA dehydrogenase (3-HADH) is excreted in the urine of infected individuals. However, the potential use of 3-HADH as a biomarker for the diagnosis of leptospirosis using enzyme-linked immunosorbent assay (ELISA) has not been investigated. A technique that identifies in a patient in urine sample will be valuable in regular diagnostics and epidemic scenarios, as opposed to existing serological approaches. This study aimed to develop and evaluate an ELISA that can detect 3-HADH in the urine of patients with confirmed acute leptospirosis and to assess its potential as a screening test for leptospirosis. Laboratory confirmation of acute leptospirosis was done by -nested polymerase chain reaction (PCR) of plasma samples from suspected patients. ELISA-based determination of the presence of 3-HADH in the urine of PCR-positive patients versus PCR-negative patients matched for fever date was performed by coating ELISA plates with urine supernatants and using rabbit anti-3-HADH as the primary antibody. Receiver operating characteristic curve analysis was used to determine the cutoff values for the ELISA. The diagnostic measures between the PCR-positive and PCR-negative patients were compared using the Mann-Whitney U test. In total, 158 febrile patients were assessed, of whom 121 (76.6 %) were male. Of the 15 nested PCR-positive patients, 12 were in the acute phase of the febrile illness. The best cutoff was an average optical density (OD) value of 0.2200 for febrile patients. Sensitivity and specificity were 83.33% [95 % confidence interval (CI), 51.59-97.91 %) and 83.33 % (95 % CI, 76.05-89.13 %), respectively. The OD values for PCR-positive patients in the acute phase of the disease (≤7 days of fever) were significantly higher than those for PCR-negative patients (<0.001, =114.0, =-4.946). Detection of 3-HADH in urine by ELISA appears to be promising for the screening of acute leptospirosis in suspected patients.
PubMed: 38868371
DOI: 10.1099/acmi.0.000651.v4 -
Parasitology Research Jun 2024Rat lungworm disease or neuroangiostrongyliasis is a cerebral parasitic infection that affects humans and animals alike. Its clinical signs and symptoms can range from...
Rat lungworm disease or neuroangiostrongyliasis is a cerebral parasitic infection that affects humans and animals alike. Its clinical signs and symptoms can range from mild self-resolving to serious life-threatening conditions. Studies suggest therapeutic interventions during the early stages of infection to be more effective than in later stages. However, early diagnosis of infection is usually problematic without the knowledge of exposure and/or detection of the parasite's DNA or antibody against the parasite in the cerebrospinal fluid. This requires a lumbar puncture, which is an invasive procedure that generally requires hospitalization. This study evaluates an affordable and less invasive alternative to detect parasitic DNA by PCR from the peripheral blood of potentially infected animals. Blood samples from 58 animals (55 dogs and 3 cats) with clinical suspicion of infection were submitted to our lab between February 2019 and August 2022 by local, licensed veterinarians. DNA was extracted from whole blood, plasma, serum, and/or packed cells using the Qiagen DNeasy Blood & Tissue Kit as per the manufacturer's protocol. All 58 animals were tested by real-time PCR using the AcanITS1 assay and 32 of these animals (31dogs; 1 cat) were also tested using the AcanR3990 assay. The PCR results for both assays were classified into strongly positive > positive > weakly positive > negative, and equivocal for ambiguous results, based on the strength of the signal. The percent infection detected using the AcanITS1 and AcanR3990 assays was 12.72% (7/55) and 20.68% (6/29), respectively. The overall percent infection detected was 34.37% (11/32), with only two animals testing positive by both assays. The three cats involved in this study tested negative by both assays. These results are promising and warrant further investigations to increase sensitivity including variables that might affect detection in the blood, such as parasite load, and laboratory methodologies.
Topics: Animals; Angiostrongylus cantonensis; Strongylida Infections; Real-Time Polymerase Chain Reaction; Cats; Cat Diseases; Dogs; Dog Diseases; Sensitivity and Specificity; DNA, Helminth
PubMed: 38862687
DOI: 10.1007/s00436-024-08251-9 -
Scientific Reports Jun 2024Cardiotrophin-like cytokine factor 1 (CLCF1) is an IL-6 family cytokine with neurotrophic and immuno-modulating functions. CLCF1 mRNA has been detected in primary and...
Cardiotrophin-like cytokine factor 1 (CLCF1) is an IL-6 family cytokine with neurotrophic and immuno-modulating functions. CLCF1 mRNA has been detected in primary and secondary lymphoid organs, and up-regulation of CLCF1 mRNA levels has been associated with the T helper (Th) 17 polarization. However, information regarding CLCF1 expression by immune cells at the protein level remains scarce. We have developed a methodology that uses a monoclonal antibody (mAb) directed against CLCF1 for the detection of human and mouse CLCF1 by flow cytometry. We have successfully detected CLCF1 protein expression in cells from the mouse pro-B cell line Ba/F3 that were transduced with CLCF1 cDNA. Interestingly, we found that the anti-CLCF1 mAb inhibits CLCF1 biological activity in vitro by binding to an epitope that encompasses site III of the cytokine. Moreover, we have detected CLCF1 expression in mouse splenic T cells, as well as in vitro differentiated Th1 cells. The specificity of the fluorescence signal was demonstrated using Clcf1-deficient lymphocytes generated using a conditional knock-out mouse model. The detection of CLCF1 protein by flow cytometry will be a valuable tool to study CLCF1 expression during normal and pathological immune responses.
Topics: Animals; Flow Cytometry; Mice; Humans; Antibodies, Monoclonal; Cytokines; Mice, Knockout; Cell Line; Th1 Cells
PubMed: 38858477
DOI: 10.1038/s41598-024-64101-9 -
Journal of Feline Medicine and Surgery Jun 2024The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using...
OBJECTIVES
The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using blood serum and the urinary lateral flow assay (LFA), for the detection of in cats with histoplasmosis.
METHODS
Eight client-owned domestic cats diagnosed with histoplasmosis were selected based on cytological, histopathological, mycological, molecular or antigenic techniques. The blood serum of these animals was tested in a semi-quantitative indirect IgG antibody EIA for the detection of . Urine samples were tested for antigen using LFA.
RESULTS
Five cats were seropositive on IgG EIA (5/8, with diagnostic sensitivity equal to 62.5%; 95% confidence interval [CI] 24.5-91.5) and five cats were positive on antigen LFA (5/7, with diagnostic sensitivity equal to 71.4%; 95% CI 29.0-96.3). The combined diagnostic sensitivity when interpreted in parallel was 87.5% (7/8, 95% CI 47.3-99.7). The specificity for the anti- IgG EIA was 100% (95% CI 71.5-100) and for the antigen LFA it was also 100% (95% CI 71.5-100).
CONCLUSIONS AND RELEVANCE
The semi-quantitative indirect IgG antibody EIA for the detection of in blood serum and the urinary LFA for the detection of the same agent emerge as new minimally invasive diagnostic techniques that can assist in the approach to disseminated and pulmonary feline histoplasmosis, especially when both techniques are considered together.
Topics: Cats; Animals; Histoplasmosis; Cat Diseases; Histoplasma; Sensitivity and Specificity; Male; Female; Antibodies, Fungal; Immunoenzyme Techniques; Immunoglobulin G
PubMed: 38857445
DOI: 10.1177/1098612X241248984