The complement system and human autoimmune diseases

Journal of Autoimmunity, Journal Year: 2022, Volume and Issue: 137, P. 102979 - 102979

Published: Dec. 18, 2022

Genetic deficiencies of early components the classical complement activation pathway (especially C1q, r, s, and C4) are strongest monogenic causal factors for prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency C4A acquired C1q by autoantibodies frequent among patients with SLE. Here we review basis in disease, discuss complex diversity seen C4 its association provide guidance as to when clinicians should suspect test deficiencies, outline current understanding mechanisms relating autoimmunity. We focus primarily on SLE, role SLE well-established, will also other informative diseases such inflammatory arthritis myositis.

Language: Английский

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Understanding the mechanisms of viral and bacterial coinfections in bovine respiratory disease: a comprehensive literature review of experimental evidence

Veterinary Research, Journal Year: 2022, Volume and Issue: 53(1)

Published: Sept. 6, 2022

Bovine respiratory disease (BRD) is one of the most important diseases impacting global cattle industry, resulting in significant economic loss. Commonly referred to as shipping fever, BRD especially concerning for young calves during transport when they are susceptible developing disease. Despite years extensive study, managing remains challenging its aetiology involves complex interactions between pathogens, environmental and host factors. While at beginning twentieth century, scientists believed that was only caused by bacterial infections ("bovine pasteurellosis"), we now know viruses play a key role induction. Mixtures pathogenic bacteria frequently isolated from secretions animals with illness. The increased diagnostic screening data has changed our understanding pathogens contributing development. In this review, aim comprehensively examine experimental evidence all existing studies performed understand coinfections cattle. fact pneumonia not always been successfully reproduced vivo calf modelling, several attempted investigate clinical significance different pathogens. studied model induction primary viral infection followed secondary superinfection, strong suggesting could potentially be common scenarios onset. Different vitro indicated priming may increase adherence colonization tract, possible mechanism underpinning bronchopneumonia onset addition, few on demonstrated also pathogenicity and, similarly, dual two severity lesions. Therefore, pathogen dynamics hypothesized which limited superinfection.

Language: Английский

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The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Aug. 29, 2023

Objective To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and rate pneumonia caused by related to checkpoint inhibitors (CIP) in patients with non-small cell cancer (NSCLC) who are getting immunotherapy (ICIs). Patients methods 507 NSCLC received at least two ICI treatments between June 2020 December 2022 Affiliated Hospital Kunming University Science Technology(AHKUST) were included a retrospective cohort study. Based on whether there was concurrent BLI diagnosis from high-resolution CT scans chest, divided into groups: 238 group (NSCLC-BLI group), 269 alone group. The collected therapeutic outcome measures objective response (ORR), progression-free survival (PFS), overall (OS), incidence CIP. We analyzed effect efficacy treatment CIP patients.Inclusion criteria based staged I IV according 8th edition International Association for Lung Cancer Research (IASLC) Results NSCLC-BLI showed superior ORR when treated ICIs. Multifactorial logistic regression Cox analyses, adjusted confounders, identified as an independent positive prognostic factor (HR=0.482, 95%CI: 0.391-0.550; P<0.001) PFS (HR=0.619; 0.551-0.771; P<0.001). No correlation OS found. Out 26 cases CIP, 12 14 group, no significant difference (P=0.145). Conclusion receiving show compared without increased risk, positioning predictive improved outcomes However, study has limitations including its nature lacking data bacteria types levels, which could influence outcomes.

Language: Английский

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Performance of targeted next-generation sequencing in the detection of respiratory pathogens and antimicrobial resistance genes for children

Journal of Medical Microbiology, Journal Year: 2023, Volume and Issue: 72(11)

Published: Nov. 1, 2023

Introduction. Respiratory tract infection, which is associated with high morbidity and mortality, occurs frequently in children. At present, the main diagnostic method culture. However, low pathogen detection rate of culture approach prevents timely accurate diagnosis. Fortunately, next-generation sequencing (NGS) can compensate for deficiency culture, its application clinical diagnostics has become increasingly available.Gap Statement. Targeted NGS (tNGS) a platform that select enrich specific regions before data enter pipeline. performance tNGS respiratory pathogens antimicrobial resistance genes (ARGs) infections children unclear.Aim methodology. In this study, we estimated ARGs 47 bronchoalveolar lavage fluid (BALF) specimens from using conventional susceptibility testing (AST) as gold standard.Results. RPIP (Respiratory Pathogen ID/AMR enrichment) generated almost 500 000 reads each specimen. pathogens, showed targeted superiority detecting difficult-to-culture bacteria, including Mycoplasma pneumoniae. Compared results sensitivity specificity were 84.4 % (confidence interval 70.5-93.5 %) 97.7 (95.9 -98.8%), respectively. Moreover, single infection was detected 10 BALF specimens, multiple 34, largest number bacterial/viral coinfections. Nevertheless, there also three where no detected. Furthermore, analysed drug containing Streptococcus pneumoniae, 25 out study. A total 58 tetracycline, macrolide-lincosamide-streptogramin, beta-lactams, sulfonamide aminoglycosides identified by 19 patients. Using AST standard, coincidence rates erythromycin, penicillin sulfonamides 89.5, 79.0, 36.8 42.1 %, respectively.Conclusion. These demonstrated detection, particularly well predicting to erythromycin significance diagnosis pathogenic guidance treatment.

Language: Английский

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Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(1), P. 41 - 41

Published: Jan. 4, 2024

Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 HM proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from 2000-2020. Seventeen out sixty-three (27.0%) had GNRs (most

Language: Английский

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The breathtaking world of human respiratory in vitro models: Investigating lung diseases and infections in 3D models, organoids, and lung‐on‐chip

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(3)

Published: Feb. 15, 2024

Abstract The COVID‐19 pandemic illustrated an urgent need for sophisticated, human tissue models to rapidly test and develop effective treatment options against this newly emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Thus, in particular, the last 3 years faced extensive boost pulmonary model development. Nowadays, 3D models, organoids lung‐on‐chip, perfusion, or precision‐cut lung slices are used study complex research questions primary cells. These provide physiologically relevant systems studying SARS‐CoV‐2 and, of course, other pathogens, but they are, too, suited pathologies, such as CF, chronic obstructive disease, asthma, more detail terms viral infection. With these cornerstone has been laid further advancing organs by, example, inclusion several immune cell types humoral components, combination with microfluidic organ‐on‐chip devices, standardization harmonization devices reliable reproducible drug vaccine testing high throughput.

Language: Английский

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The Impact of Multiplex PCR in Diagnosing and Managing Bacterial Infections in COVID-19 Patients Self-Medicated with Antibiotics

Antibiotics, Journal Year: 2022, Volume and Issue: 11(4), P. 437 - 437

Published: March 24, 2022

The multiplex PCR is a powerful and efficient tool that was widely used during the COVID-19 pandemic to diagnose SARS-CoV-2 infections has applications for bacterial identification, as well determining resistance antibiotics. Therefore, this study aimed determine usability of PCR, especially in patients self-medicated with antibiotics, where cultures often give false-negative results. A cross-sectional developed two units, 489 eligible were included antibiotic takers non-antibiotic takers. Antibiotic mostly over-the-counter medication; they suffered significantly more chronic respiratory conditions most cephalosporins (41.4%), macrolide (23.2%), penicillin (19.7%). disease severity these higher than takers, superinfections common finding same group (63.6%). had longer hospital ICU admissions, although mortality rate not bacteria involved secondary Staphylococcus aureus (22.2%), Pseudomonas aeruginosa (27.8%), Klebsiellaspp (25.0%). Patients self-medicating antibiotics rates multidrug resistance. test accurate identifying resulted quicker initiation therapeutic compared instances culture initially performed, an average 26.8 h vs. 40.4 h, respectively. stay also shorter by 2.5 days when initial assessment infections. When adjusted age, severity, pulmonary disease, use represented significant independent risk factor prolonged hospitalization (AOR = 1.21). Similar findings observed smoking status 1.44), superinfection 1.52), performing only conventional 1.17), duration 48 sampling from time admission 1.36). Multiplex may be very effective method diagnosing individuals Utilizing strategy screen who exhibit signs sepsis clinical deterioration will result faster recovery period hospitalization.

Language: Английский

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The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(2)

Published: Jan. 24, 2023

Concurrent infections with multiple pathogens are often described in cattle respiratory illness. However, how the host-pathogen interactions influence clinical outcome has been only partially explored this species. Influenza D virus (IDV) was discovered 2011. Since then, IDV detected worldwide different hosts. A significant association between and bacterial sick shown epidemiological studies, especially Mycoplasma bovis. In an experimental challenge, aggravated M. bovis-induced pneumonia. mechanisms through which drives increased susceptibility to superinfections remain unknown. Here, we used organotypic lung model precision-cut slices study interplay bovis coinfection. Our results show that a primary infection promotes superinfection by increasing replication ultrastructural damages pneumocytes. our model, impaired innate immune response triggered decreasing expression of several proinflammatory cytokines chemokines important for cell recruitment clearance. Stimulations agonists cytosolic helicases Toll-like receptors (TLRs) revealed activation RIG-I/MDA5 desensitizes TLR2 activation, similar what observed infection. The cross talk these two pattern recognition leads nonadditive response, alters TLR2-mediated cascade controls These highlight were not so far improve understanding bovine host-microbe pathogenesis. IMPORTANCE spread influenza population, question about impact on disease (BRD) remains still unanswered. Animals affected BRD coinfected pathogens, viruses bacteria. particular, suspected enhance secondary superinfections. use ex vivo tissue effects increases pathogen seems activate pathways inhibit against This may allow increase its proliferation delay clearance from tissue. suggest could have negative pathology cattle.

Language: Английский

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Coinfections in the lung: How viral infection creates a favorable environment for bacterial and fungal infections

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(5), P. e1011334 - e1011334

Published: May 4, 2023

While it is well established that secondary bacterial pneumonia plays a significant role in the morbidity and mortality of patients with severe respiratory viral infections, bacteria are not only threat for these patients.Over last decade, there has been rise number infections acquiring fungal specifically filamentous mold Aspergillus fumigatus [1,2].Importantly, while occur less frequently than pneumonias, they associated greater [1].Because immune suppression major risk factor [3], may create transient suppressed state allowing to occur.Here, we discuss what have learned about how antiviral host responses lung environment susceptible infection this translate into susceptibility.

Language: Английский

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Bacterial Community- and Hospital-Acquired Pneumonia in Patients with Critical COVID-19—A Prospective Monocentric Cohort Study

Antibiotics, Journal Year: 2024, Volume and Issue: 13(2), P. 192 - 192

Published: Feb. 16, 2024

The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence community- and hospital-acquired (CAP HAP) its effect mortality in critically ill admitted intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 31 December 2022. secondary objectives this include identifying etiology CAP HAP exploring capabilities diagnostic tools, a focus inflammatory biomarkers. Data were collected from electronic information hospital system, encompassing biomarkers, microbiological findings, daily visit records, subsequently evaluated by ICU physicians clinical microbiologists. Out 171 suffering critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically who experienced exhibited higher compared without any infection, rates 38% 56% versus 11%, respectively. In most frequent causative agents chlamydophila mycoplasma; Enterobacterales, which multidrug-resistant 71% cases; Gram-negative non-fermenting rods; Staphylococcus aureus. Notably, no strains Streptococcus pneumoniae detected, only single strain each Haemophilus influenzae Moraxella catarrhalis was isolated. etiologic causing Enterobacterales rods. Based presented results, commonly used biochemical markers demonstrated poor predictive accuracy. To confirm diagnosis our patient cohort, it necessary assess initial values (particularly procalcitonin), consider signs indicative and/or rely positive findings. For diagnostics, appropriate conduct regular detailed examinations (with evaluating respiratory functions) closely monitor dynamics (preferably Interleukin-6).

Language: Английский

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