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12 pages, 375 KB  
Article
High Prevalence of Occult Hepatitis B Virus Co-Infection Identified in Treponema Pallidum-Positive Blood Donations: Implications for HBV Risk Reduction
by Xianlin Ye, Xiaoxuan Xu, Jinfeng Zeng, He Xie, Jujun Sun, Baoren He and Limin Chen
Pathogens 2026, 15(7), 776; https://doi.org/10.3390/pathogens15070776 - 22 Jul 2026
Abstract
Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood [...] Read more.
Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood donors globally. In addition, sexual contact with individuals chronically infected with hepatitis B virus (HBV) is recognized as one of the primary routes of HBV transmission. Blood donors may acquire HBV infection through sexual contact with chronically infected partners, particularly with occult hepatitis B infections (OBIs), which are characterized by intermittent and extremely low viral loads. Therefore, the prevalence of OBIs among syphilis-positive blood donations and the corresponding risks to blood safety require further investigation. This study aimed to investigate the prevalence of OBIs among syphilis-positive blood donors and assess the surrogate value of TP testing for evaluating OBI-related risks to blood supply. After routine screening using serological assays and nucleic acid testing (NAT), blood donation samples with positive anti-TP enzyme-linked immunosorbent assay (ELISA) results were collected and further confirmed by the Treponema Pallidum Particle Agglutination Assay (TPPA). For blood donations confirmed positive for syphilis, further tests were performed to characterize whether the donations had HBV co-infection, including electrochemiluminescence immunoassay (ECLI) for the detection of hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), anti-hepatitis B e antibody (anti-HBe), and anti-hepatitis B core antibody (anti-HBc). Additionally, quantitative real-time polymerase chain reaction (qPCR) was used for HBV DNA quantification, and nested PCRs for the S and basal core promoter/precore (BCP/PC) region were conducted in combination with high-volume nucleic acid extraction. Subsequently, molecular characterization of HBV DNA in these co-infected samples was carried out by DNA sequencing to analyze the viral genetic features. Of 252 anti-TP ELISA+ donations screened from 64,871 blood samples, 138 (138/250, 55.2%) donations were confirmed syphilis-positive but NAT−, among which 78 (78/138, 56.5%) were anti-HBc-positive, and 88 (88/138, 63.7%) had anti-HBs. Notably, seven donations (7/138, 5.1%) were diagnosed as OBI co-infections, and available sequence analysis revealed that three cases were genotype B and one case was genotype C. In addition, several mutations in the S region of the HBV genome were identified, including Q101R, K122R, Q129H, T131N, M133T, G145R, and Y161F mutations. Furthermore, nucleotide mutations such as T1719G, A1752T, G1896A, and A1762T/G1764A in the BCP/PC regions were also detected in these OBI donations. These mutations may contribute to the extremely low HBV viral loads and/or failure in HBsAg detection, collectively leading to OBIs. These data indicate that syphilis screening of blood donors has potential to serve as an additional safeguard measure for excluding donations co-infected with OBIs. The high prevalence of undetected OBIs in syphilis-positive blood donors further supports that syphilis screening has the potential to serve as a surrogate marker for HBV-related risks in the blood supply. Full article
(This article belongs to the Special Issue Advances in the Epidemiology of Human Infectious Diseases)
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22 pages, 2348 KB  
Review
Challenges in Differential Diagnosis and Management of Lymphoepithelial Sialadenitis (LESA): A Scoping Review
by Miruna Bratiloveanu, Mihai Dumitru, Bogdan Banica, Oana Maria Patrascu, Crenguta Serboiu, Andreea Marinescu, Alina Oancea, Daniela Vrinceanu and Adrian Costache
Life 2026, 16(7), 1199; https://doi.org/10.3390/life16071199 - 20 Jul 2026
Viewed by 118
Abstract
Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone [...] Read more.
Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Objective: This scoping review mapped current evidence on diagnostic challenges, differential diagnostic criteria, management strategies, and surveillance considerations for LESA. Eligibility criteria: Sources were selected using the Population–Concept–Context framework and included the literature addressing salivary gland lymphoepithelial lesions, LESA, Sjögren’s disease-associated salivary gland involvement, or related lymphoid-rich salivary gland disorders published from 2010 onward. Sources of evidence and charting methods: Google Scholar was searched, records were screened in sequential stages, and relevant data were charted narratively across clinical, serological, imaging, histopathological, immunophenotypic, molecular, therapeutic, and follow-up domains. Results: Thirty-seven sources were included. The evidence indicates that LESA is usually characterized by chronic lymphoplasmacytic inflammation, acinar atrophy, lymphoepithelial lesions, and preserved lobular architecture; however, these findings may overlap with early or established MALT lymphoma. Immunohistochemistry, assessment of light-chain restriction, clonality testing, serological markers, and imaging are useful adjuncts, but no single test is independently definitive. Conservative management and symptomatic care are appropriate for stable disease, whereas corticosteroids, immunomodulatory therapy, sialendoscopy, surgery, radiotherapy, or systemic lymphoma therapy may be considered according to clinical context. Conclusions: LESA requires integrated clinicopathological interpretation and multidisciplinary follow-up. Key evidence gaps include the absence of standardized LESA-specific diagnostic criteria, limited validation of molecular and flow cytometric approaches in salivary gland specimens, and lack of consensus surveillance protocols. Full article
(This article belongs to the Special Issue The Oral-Systemic Link in Chronic Mucosal Diseases)
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15 pages, 12185 KB  
Case Report
DNAJB9 in Fibrillary Glomerulonephritis: Diagnostic Biomarker, Putative Autoantigen, or Disease-Associated Scaffold? A Case-Based Narrative Review
by Larrisa Lebedev, Mahmud Mansur, Mustafa Seh, Elena Rotshild, Ornit Itzhaki, Alexander Wechsler, Anna Tobar and Nomy Levin Iaina
Life 2026, 16(7), 1186; https://doi.org/10.3390/life16071186 - 17 Jul 2026
Viewed by 149
Abstract
Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily [...] Read more.
Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily ultrastructural diagnosis into a molecularly recognizable disease. However, the pathogenic significance of DNAJB9 remains unresolved: it may represent a highly specific biomarker, a putative autoantigen, a chaperone-associated scaffold, or a marker of disturbed protein quality control. We report two patients with positive glomerular DNAJB9 staining and markedly divergent clinical phenotypes. The first patient, a 58-year-old man, presented with severe acute kidney injury, nephritic urinary sediment, severe hypertension, crescentic immune-complex glomerulonephritis, and dialysis-requiring kidney failure. Electron microscopy and IgG subclass staining were unavailable; therefore, the findings were interpreted as probable rather than definitive DNAJB9-positive FGN. Diagnostic and causal interpretation was further complicated by concurrent Klebsiella pneumoniae urinary tract infection, mild bilateral hydronephrosis, acute tubulointerstitial injury, and severe hypertension. Kidney function did not recover despite glucocorticoids and cyclophosphamide, but the adverse outcome and treatment response cannot be attributed to FGN alone. The second patient, a 66-year-old woman, presented with chronic proteinuria, preserved kidney function, inactive urinary sediment, and lupus-like serologic findings. Electron microscopy demonstrated randomly arranged, nonbranching 13–19 nm fibrils, and DNAJB9 staining confirmed FGN. She was managed with angiotensin receptor blockade and dapagliflozin, with reduction of proteinuria to below 1 g/day. Together with previously published cohorts, these cases illustrate the diagnostic value of DNAJB9 staining and the potential clinicopathologic heterogeneity of FGN. However, Case 1 should be considered a clinically confounded, hypothesis-generating example and not definitive evidence that FGN alone caused the crescentic presentation, dialysis dependence, or lack of response to immunosuppression. Full article
(This article belongs to the Special Issue Pathogenesis and Novel Treatment for Kidney Diseases)
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13 pages, 380 KB  
Article
Beyond the Surface: Antinuclear Antibodies in Rheumatoid Arthritis—Experiences from a Single-Center, Cross-Sectional Observational Study
by Hanna Cholerzyńska, Gabriela Kot, Łukasz Świątek and Bogna Grygiel-Górniak
Antibodies 2026, 15(4), 58; https://doi.org/10.3390/antib15040058 - 10 Jul 2026
Viewed by 248
Abstract
Background: Antinuclear antibodies (ANA) can be detected in patients with rheumatoid arthritis (RA) and pose many diagnostic challenges, especially when RA presents an atypical course and requires differentiation from other systemic connective tissue diseases (sCTDs). This study assessed ANA fluorescence patterns and immunoblot [...] Read more.
Background: Antinuclear antibodies (ANA) can be detected in patients with rheumatoid arthritis (RA) and pose many diagnostic challenges, especially when RA presents an atypical course and requires differentiation from other systemic connective tissue diseases (sCTDs). This study assessed ANA fluorescence patterns and immunoblot profiles, as well as the relationships between ANA titers, antibody expression intensity, and markers of disease activity in patients with RA. Methods: This single-center, cross-sectional, observational study included 81 RA patients (53 ANA-positive) meeting the 2010 ACR/EULAR classification criteria. ANA titers and fluorescence patterns were assessed using indirect immunofluorescence. Anti-extractable nuclear antigen (ENA) autoantibody profiles and expression intensity were assessed using immunoblot analysis. Demographic, clinical, and laboratory data were obtained. Spearman’s rank correlation coefficient was used to analyze the relationship between ANA titers and selected variables. Univariate and multivariate logistic regression analyses were performed to identify factors associated with ANA positivity. Results: The cohort consisted primarily of women (86.4%) with moderate disease activity. ANA fluorescence patterns were heterogeneous, with nucleolar and homogeneous patterns most frequently observed. Immunoblot analysis also revealed diverse autoantibody profiles without a clearly dominant specificity. Ro-52, SS-A, and Sm antibodies were detected more frequently, although their prevalence remained relatively low. No statistically significant correlations were found between ANA titers and inflammatory markers, serological parameters, or disease activity indices. Conclusions: RA patients with positive ANA demonstrated marked immunological heterogeneity, without concomitant symptoms of sCTD. A positive result in RA may reflect generalized immune dysregulation rather than a distinct clinical subtype. Further studies with larger cohorts are needed to clarify the clinical significance of ANAs in rheumatoid arthritis. Full article
(This article belongs to the Section Antibody-Based Diagnostics)
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26 pages, 3001 KB  
Review
The Basophil Activation Test in Allergy Diagnostics: Clinical Applications, Methodological Challenges, and Proposed Clinical Frameworks
by Marina Izmailovich, Aizhan Kabyldina, Zamira Seilkhan, Aruzhan Zhussip, Raushan Kozhanova, Tair Nurpeissov, Gulzada Uteubaeva, Olga Kazimirova, Alyona Lavrinenko, Lyubov Brizitskaya, Elina Suleimanova and Zarina Shaikhina
Cells 2026, 15(14), 1241; https://doi.org/10.3390/cells15141241 - 9 Jul 2026
Viewed by 189
Abstract
The basophil activation test (BAT) is a modern in vitro functional assay used for the diagnosis of immunoglobulin E-mediated allergic reactions. The method is based on flow cytometric assessment of activation marker expression on peripheral blood basophils after stimulation with specific allergens. BAT [...] Read more.
The basophil activation test (BAT) is a modern in vitro functional assay used for the diagnosis of immunoglobulin E-mediated allergic reactions. The method is based on flow cytometric assessment of activation marker expression on peripheral blood basophils after stimulation with specific allergens. BAT has gained increasing clinical relevance in allergology, particularly in patients with anaphylaxis risk, polysensitization, drug hypersensitivity, and inconclusive skin or serological test results. This narrative review summarizes current evidence on the diagnostic performance and clinical applications of BAT in food allergy, drug hypersensitivity, Hymenoptera venom allergy, latex sensitization, and allergen immunotherapy monitoring. The review discusses the immunological mechanisms of basophil activation, the role of CD63 and CD203c, methodological aspects of the assay, sensitivity and specificity data, and advantages and limitations compared with conventional diagnostic approaches. Particular attention is given to protocol standardization, interpretation criteria, and the problem of non-responder patients. Current evidence indicates that BAT demonstrates high specificity and provides functional assessment of clinically relevant allergic reactions. In addition, this review proposes practical clinical frameworks for integrating BAT into allergy diagnostic pathways and for managing inconclusive or non-responder BAT results. Further standardization, multiplex formats, and automated analytical approaches may expand its role in personalized allergy diagnostics. Full article
(This article belongs to the Special Issue Allergy and Immunity)
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17 pages, 922 KB  
Article
Reassessing Regional Tick-Borne Encephalitis Endemicity in Poland Through Seroprevalence Analysis in Blood Donors, 2021–2022
by Katarzyna W. Pancer, Magdalena Rosińska, Gerhard Dobler, Daniel Rabczenko, Agnieszka Kołakowska-Kulesza, Beata Gad, Anna Poznańska and Piotr Grabarczyk
Pathogens 2026, 15(7), 720; https://doi.org/10.3390/pathogens15070720 - 8 Jul 2026
Viewed by 275
Abstract
TBEV is a major cause of viral central nervous system infections in Europe, with heterogeneous geographical distribution and substantial underdiagnosis in low-incidence regions. This study aimed to evaluate the validity of regional TBE risk classification in Poland by combining surveillance-based incidence data with [...] Read more.
TBEV is a major cause of viral central nervous system infections in Europe, with heterogeneous geographical distribution and substantial underdiagnosis in low-incidence regions. This study aimed to evaluate the validity of regional TBE risk classification in Poland by combining surveillance-based incidence data with serological markers of TBEV exposure. Plasma samples from 5541 blood donors residing in nine regions were tested by anti-TBEV IgG ELISA, followed by confirmatory VNT, IFA, and anti-NS1 IgG ELISA to differentiate infection-induced from vaccine-induced antibodies. Regions were classified based on average TBE incidence registered in surveillance systems in 2015–2019. Overall, 272 (4.9%) donors were positive in TBEV IgG ELISA and 177 (3.2%) also in a confirmatory assay. Seroprevalence expressed by markers consistent with past TBEV infection (anti-NS1 IgG) was estimated at 0.13% (95% CI 0.05–0.26%), ranging from 0.0% to 0.33% by voivodeship, whereas vaccine-induced immunity accounted for the majority of samples with detected specific antibodies (3.1%). Surprisingly, seroprevalence in a highly affected region (0.29%) was at the same level as in one that was less affected (0.33%). Moreover, all except one seropositive donor lived in urban areas. In four out of nine voivodeships, no anti-NS1 TBEV IgG was detected. By utilising precise laboratory algorithms, we demonstrated a much lower seroprevalence that estimated from prior research relying on screening tests. In addition, we confirmed low vaccination coverage. Integrating sero-epidemiological data with surveillance systems may improve risk assessment and inform targeted prevention strategies. Full article
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20 pages, 12386 KB  
Article
Deciphering the Multi-Target Mechanisms of Sheshang Jiedu Decoction Against Snake Envenomation-Induced Acute Hepatic Dysfunction: An Integrated Multi-Omics Study
by Linfeng Wang, Jianqi Zhao, Fangwei Xia, Dianyun Sun, Qian Lei, Meilin Liu, Xiao Shi, Yang Yang and Chunhong Huang
Pharmaceuticals 2026, 19(7), 1050; https://doi.org/10.3390/ph19071050 - 7 Jul 2026
Viewed by 360
Abstract
Objective: This study aimed to experimentally validate the hepatoprotective efficacy of Sheshang Jiedu Decoction (SSJDD) against Deinagkistrodon acutus (D. acutus) venom-induced acute liver injury (ALI) and systematically elucidate its multicomponent, multitarget mechanisms using an integrated multi−omics strategy. Methods: SSJDD [...] Read more.
Objective: This study aimed to experimentally validate the hepatoprotective efficacy of Sheshang Jiedu Decoction (SSJDD) against Deinagkistrodon acutus (D. acutus) venom-induced acute liver injury (ALI) and systematically elucidate its multicomponent, multitarget mechanisms using an integrated multi−omics strategy. Methods: SSJDD constituents and serum-absorbed metabolites were profiled using UPLC-Q-Exactive HFX MS, and potential targets were predicted via network pharmacology. An in vivo model was established by intraperitoneally injecting Kunming mice with D. acutus venom, followed by a 7-day oral SSJDD intervention. The therapeutic efficacy was assessed by histopathological examination, serological analysis, and detection of oxidative stress markers in liver tissues. Label-free quantitative proteomics was performed on murine livers to map dynamic protein alterations and signaling cascades. Results: Integrated metabolomic and network analyses identified 15 primary active serum metabolites converging on core regulatory targets, including TP53, AKT1, and CASP3. In vivo, SSJDD dose-dependently ameliorated venom-induced lobular necrosis, suppressed elevated transaminases, and restored redox homeostasis without intrinsic hepatotoxicity. Quantitative proteomics revealed that venom triggered profound acute oxidative stress and coagulopathies, progressing to chronic metabolic disruption. SSJDD intervention substantially attenuated these proteomic alterations—reducing differentially expressed proteins by 84%—steering the hepatic microenvironment toward baseline homeostasis. Enrichment analyses demonstrated that these effects were primarily driven by modulating the coagulation-inflammation axis and the PI3K−Akt signaling pathway. Conclusions: SSJDD provides robust protection against D. acutus venom-induced ALI. Its active metabolites synergistically orchestrate hepatic repair and restore microenvironmental stability, primarily by targeting the PI3K−Akt pathway and regulating the coagulation-inflammation axis. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 4723 KB  
Article
Completeness of MMR Vaccination and Durability of Vaccine-Induced Antibody Responses in Children with Inflammatory Bowel Disease
by Ivan S. Samolygo, Alexey A. Tinkov, Marina A. Manina, Anton S. Antishin, Albina S. Pestova, Ekaterina A. Yablokova, Ekaterina V. Prutskova, Mikhail P. Kostinov and Svetlana I. Erdes
Biomedicines 2026, 14(7), 1526; https://doi.org/10.3390/biomedicines14071526 - 7 Jul 2026
Viewed by 318
Abstract
Background: Children with IBD are at increased risk of suboptimal maintenance of vaccine-induced immunity, particularly when the MMR vaccination course is incomplete before diagnosis and initiation of immunosuppressive therapy. We conducted a prospective study to evaluate the durability of antibody responses to measles, [...] Read more.
Background: Children with IBD are at increased risk of suboptimal maintenance of vaccine-induced immunity, particularly when the MMR vaccination course is incomplete before diagnosis and initiation of immunosuppressive therapy. We conducted a prospective study to evaluate the durability of antibody responses to measles, mumps, and rubella in pediatric IBD patients and to determine how completeness of MMR vaccination influences long-term antibody persistence over 12 months. Methods: Sixty children with IBD were included. Demographic characteristics, clinical disease activity (PUCAI/PCDAI), inflammatory markers (CRP, ESR), and fecal calprotectin were extracted from electronic medical records. Vaccination completeness was ascertained from documented immunization history. Serum antibodies to measles, rubella, and mumps were measured at baseline and after 12 months. Seroprotection was defined using standard laboratory thresholds. Antibody decay over time was assessed with paired non-parametric tests, and time to loss of seroprotection was analyzed using Cox proportional hazards models. In addition, Bayesian ANOVA modeling was applied to quantify evidence for differences in antibody concentrations and decay kinetics according to vaccination status. Results: Overall, 66.7% of patients had completed the full MMR vaccination course. At baseline, seroprotection rates were 48.3% for measles, 76.7% for rubella, and 70% for mumps. After 12 months, median antibody concentrations declined significantly for all three antigens. Corresponding seroprotection rates changed to 46.7% for measles (p = 0.414), 70% for rubella (p = 0.046), and 66.7% for mumps (p = 0.157). Incomplete MMR vaccination was identified as a major modifiable risk factor for accelerated antibody waning in children with IBD. Cox regression demonstrated that incompletely vaccinated patients had a 2.13-fold higher risk of losing measles seroprotection (95% CI 1.07–4.24; p = 0.032), a 5.27-fold higher risk for rubella (95% CI 1.86–14.95; p = 0.002), and a 4.82-fold higher risk for mumps (95% Cl 1.68–13.85; p = 0.004). Bayesian analyses provided decisive evidence that vaccination completeness strongly influences baseline antibody levels. Conclusions: Incomplete MMR vaccination is associated with markedly reduced durability of vaccine-induced immunity to measles, mumps, and rubella in children with IBD. These findings underscore the need for systematic prevaccination screening, timely completion of age-appropriate vaccination before initiation of immunosuppressive therapy when feasible, and individualized serological monitoring to identify patients at highest risk of vaccine-preventable infections. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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16 pages, 1904 KB  
Article
Molecular Characterization, SNP-Based Strain Profiling, and Seroprevalence of Bacillus anthracis in Ruminants in Jordan
by Amin A. Aqel, Mohammad Abu Lubad, Hamed Alzoubi, Daniel S. Schabacker, Sara Forrester, Scott Schlueter, Mark Khemmani, Alan J. Wolfe, Tahir Yaqub, Muhammad Waqar Aziz, Mohammed Alsbou and Yasser Gaber
Microorganisms 2026, 14(7), 1483; https://doi.org/10.3390/microorganisms14071483 - 7 Jul 2026
Viewed by 280
Abstract
Anthrax is an endemic and undercharacterized zoonotic disease in the Middle East, including Jordan. Between 2018 and 2020, we conducted a comprehensive investigation of 13 confirmed anthrax outbreaks in Jordan, analyzing 822 samples from animal farm environments, including carcasses, asymptomatic livestock, and abiotic [...] Read more.
Anthrax is an endemic and undercharacterized zoonotic disease in the Middle East, including Jordan. Between 2018 and 2020, we conducted a comprehensive investigation of 13 confirmed anthrax outbreaks in Jordan, analyzing 822 samples from animal farm environments, including carcasses, asymptomatic livestock, and abiotic environmental surfaces. All samples were tested by qPCR targeting the chromosomal marker (ba177) and the plasmid marker pXO1 (pag). Among carcass samples, 75/195 (38.5%) were ba177-positive, of which 81% harbored the pXO1. Of specimens from live-animals and from environmental surfaces, 218/627 (35%) were positive by qPCR, likely reflecting environmental contamination during active outbreak periods. Serological analysis using anti-protective antigen (PA) ELISA revealed a high seroprevalence of 53% (75/141) among asymptomatic animals, indicating widespread sub-clinical exposure to B. anthracis antigens and previously undocumented endemicity. An integrated approach combining qPCR with ELISA demonstrated that 11% of seropositive animals with paired swab testing also yielded swab samples that were positive by qPCR, suggesting environment-to-host transition. Molecular strain typing using canonical SNP (canSNP) analysis identified the rare sublineage C.USA.A1055 within lineage C.Br.A1005 across two distinct outbreaks, suggesting the environmental persistence of this endemic lineage. Overall, our findings provide the first systematic molecular and serological surveillance baseline data for Jordan, demonstrating a complex genomic persistence and subclinical exposure landscape. This study suggests the need for enhanced surveillance strategies under the One Health framework to mitigate the risk of anthrax endemicity. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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17 pages, 5106 KB  
Article
Genetic Epidemiology of Bovine Leptospirosis: A Global Perspective from Sequence and Genome Datasets
by Luiza Aymée, Ana Luiza dos Santos Baptista Borges, Maria Isabel Nogueira Di Azevedo and Walter Lilenbaum
Animals 2026, 16(13), 2017; https://doi.org/10.3390/ani16132017 - 2 Jul 2026
Viewed by 315
Abstract
Leptospirosis is an important reproductive disease in bovine hosts, yet its epidemiology is still largely inferred from serology, which provides limited resolution in bovines. Although genetic studies based on genotyping and whole-genome sequencing approaches are increasing, a comprehensive overview is still lacking. We [...] Read more.
Leptospirosis is an important reproductive disease in bovine hosts, yet its epidemiology is still largely inferred from serology, which provides limited resolution in bovines. Although genetic studies based on genotyping and whole-genome sequencing approaches are increasing, a comprehensive overview is still lacking. We analyzed bovine-origin sequences and genome metadata from databases to characterize patterns of Leptospira species and serogroups and to describe genotyping methods and molecular markers. Metadata were retrieved from GenBank and the Institut Pasteur cgMLST databases until January 2026. Extracted variables included species, genotyping approach/markers, serological classification of isolates, sample type and origin (renal vs. genital), clinical signs, and geographic location; climates were assigned using Köppen–Geiger classification. After selection, 569 records were retrieved: 411 single-locus sequences (eight molecular markers), 95 MLST profiles, and 63 genomes, from 35 countries, with most reports from South America (57.6%). Records spanned tropical, temperate, steppe, Mediterranean, and continental-cold climates. Nine species and 14 serogroups were identified; tropical and temperate areas showed greater diversity. The main agents, L. interrogans, L. borgpetersenii, and serogroup Sejroe, were predominant and widespread. Notably, L. noguchii, L. santarosai, L. venezuelensis, and L. wolffii were mostly concentrated in the Americas. Most records were from renal samples (68.7%), indicating limited focus on genital leptospirosis, and 83.5% lacked clinical information, limiting links between strains and manifestations. Overall, bovine leptospirosis is worldwide distributed, but gaps persist in marker standardization for single-locus sequencing and genome availability. Standardized genotyping, increasing genital sampling, and improving clinical metadata are essential for refining surveillance and clarifying the role of emerging species. Full article
(This article belongs to the Section Cattle)
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13 pages, 1002 KB  
Article
Differential Binding and Neutralising Antibody Responses Across COVID-19 Severity in a Saudi Multicentre Cohort
by Mariam M. AlEissa, Nada Saleh, Ahdab A. Alsaieedi, Raghad A. AlQurashi, Esraa A. Hawsa, Muath ben Shaded, Amer M. Alshehri, Eyad Y. Abu Sarhan, Osamah T. Khojah, Walid A. Nouh, Sami S. Almudarra, Khaled I. AlAbdulkareem, Ghada Garaween, Maha Alzayer, Yusra Alyafee, Monera Alrukhayes, Reema Alduaiji, Fahad A. Almsned and Abdullah M. Assiri
Viruses 2026, 18(7), 696; https://doi.org/10.3390/v18070696 - 24 Jun 2026
Viewed by 357
Abstract
Background: Humoral immune responses to SARS-CoV-2 are well documented, yet the immunopathogenic mechanisms distinguishing severe from critical disease remain incompletely defined, particularly in Middle Eastern populations. We investigated antibody responses across levels of clinical severity in a Saudi Arabian cohort. Methods: In this [...] Read more.
Background: Humoral immune responses to SARS-CoV-2 are well documented, yet the immunopathogenic mechanisms distinguishing severe from critical disease remain incompletely defined, particularly in Middle Eastern populations. We investigated antibody responses across levels of clinical severity in a Saudi Arabian cohort. Methods: In this multicentre study, we analysed 406 participants stratified into five clinical groups: controls, asymptomatic, mild, severe, and critically ill requiring intensive care unit (ICU) admission. SARS-CoV-2-specific IgG and IgM levels were quantified alongside surrogate ACE2-RBD neutralisation activity. Associations between humoral markers, demographic factors, comorbidities, and disease severity were assessed. Results: SARS-CoV-2-specific IgG and IgM levels differed significantly across disease severity groups (p < 0.001), with higher levels observed in groups with greater clinical severity. No significant difference in IgG or IgM levels was observed between the severe and ICU groups (IgG p = 0.384; IgM p = 0.768). While binding antibody levels were associated with severity, surrogate ACE2-RBD neutralising activity did not differ significantly across groups (p = 0.209). Increasing age (χ2 = 44.5) and the presence of comorbidities (χ2 = 31.9) were associated with more severe clinical categories, whereas sex was not. Conclusions: These findings suggest that antibody levels provide useful information about exposure and immune activation, but antibody quantity alone does not fully explain the transition from severe to critical disease. The results support interpreting serological measures alongside clinical factors such as age and chronic illness. Full article
(This article belongs to the Special Issue COVID-19 Complications and Co-Infections: 2nd Edition)
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18 pages, 1685 KB  
Article
Precision Proteomic Profiling of Systemic Lupus Erythematosus—Correlating Disease Activity and Complement Levels with Clinical Phenotypes
by Jacob Skallerup, Christopher Aboo, Dorte B. Bekker-Jensen, Katherine Tran, Jie Ren, Malene Møller Jørgensen, Jonathan M. Blackburn, Anne Troldborg and Allan Stensballe
Biomedicines 2026, 14(6), 1408; https://doi.org/10.3390/biomedicines14061408 - 22 Jun 2026
Viewed by 508
Abstract
Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement [...] Read more.
Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement activation (measured through C3dg, a complement breakdown product) in SLE patients utilizing high-throughput mass spectrometry and autoantibody profiling. Methods: Plasma samples from 39 SLE patients in four mutually exclusive groups based on either disease activity scores (high/low SLEDAI) or complement activation levels (high/low C3dg) were analyzed using rapid LC-MS/MS, followed by unsupervised and supervised protein expression analysis. Complement activation was evaluated by measuring C3dg levels, and disease activity was scored using SLEDAI. Autoantibody reactivities were profiled using global autoantibody protein microarrays. Data are available via ProteomeXchange with identifier PXD066214. Results: Differential proteomic analyses revealed 25 proteins associated with SLE disease activity (high vs. low SLEDAI scores) and 25 proteins linked to complement activation levels (high vs. low C3dg). Enriched pathways indicated that adaptive immune response, classical complement activation, and immunoglobulin production correlated with disease activity, while complement activation and coagulation cascades were primarily associated with complement activation levels. Autoantibody profiling highlighted distinct reactivity patterns between subgroups, suggesting varying degrees of immune-mediated tissue damage. Conclusions: In this study, disease activity and complement activation markers were associated with overlapping yet non-identical plasma proteomic patterns in SLE. These findings support the feasibility of rapid mass spectrometry-based proteomics and autoantibody profiling for generating candidate molecular signatures in SLE. These findings serve as exploratory signatures that require validation in larger independent cohorts before they can be considered for clinical stratification and decision-making. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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33 pages, 518 KB  
Article
Sharp-Wave EEG Activity and Cytomegalovirus Exposure in Schizophrenia Spectrum Disorders: A Neuroimmune Perspective
by Mădălina Georgeta Sighencea, Marius Cornițescu and Simona Corina Trifu
J. Clin. Med. 2026, 15(12), 4841; https://doi.org/10.3390/jcm15124841 - 22 Jun 2026
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Abstract
Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG [...] Read more.
Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG features, inflammatory markers, and clinical–cognitive variables. Methods: In this prospective cross-sectional study, 123 patients with schizophrenia spectrum disorders underwent integrated clinical, cognitive, laboratory, and qualitative visual EEG assessments. CMV exposure was determined via IgG serology. Results: Global electroencephalographic EEG organization did not differ by CMV serostatus. However, a descriptive increase in resting-state sharp-wave discharges was observed in CMV-seronegative patients, independent of baseline cortical rhythms. Immunologically, CMV-seropositive individuals exhibited significantly higher total leukocyte counts, consistent with latent viral immune remodeling rather than overt systemic inflammation. Clinically, CMV-seropositive patients demonstrated descriptively higher scores on the disorganization dimension derived from the PANSS (Positive and Negative Syndrome Scale) five-factor consensus model. While these variations did not retain statistical significance after multiple testing correction, separate dimensional analyses revealed that patients exhibiting sharp waves demonstrated better overall cognitive functioning and superior performance within a memory-related item grouping. Notably, the presence of sharp-wave activity was independent of both peripheral inflammatory profiles and treatment-resistant status, underscoring a distinct electrophysiological phenotype. Conclusions: CMV exposure represents a modulating biological background associated with corrected leukocyte elevations and subtle electrophysiological variability, rather than a direct determinant of global clinical severity. The nominal EEG variations and their independent link to better-preserved memory performance highlight non-linear neuroimmune interactions. Given the cross-sectional design, these exploratory patterns warrant a non-causal interpretation but outline a foundation for future longitudinal investigations. Full article
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16 pages, 766 KB  
Article
Detection of Dengue Virus and Serological Evidence of Chikungunya and Zika Virus Exposure in Patients with Acute Febrile Syndrome in Córdoba, Colombia
by Paula A. Avilés-Vergara, Dina Ricardo-Caldera, Carlos Alberto Bolívar Pineda, Eliud Daniel Pérez Vergara, Ana Carolina Negrette Oquendo, Luis Carlos Ruiz Garces, Sara Cecilia Soto-De León and Catalina Tovar-Acero
Trop. Med. Infect. Dis. 2026, 11(6), 162; https://doi.org/10.3390/tropicalmed11060162 - 17 Jun 2026
Viewed by 534
Abstract
Background/Objectives: Arboviral diseases transmitted by Aedes mosquitoes, including Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), represent a major public health challenge in tropical regions. Their clinical similarity complicates differential diagnosis, particularly in settings of viral co-circulation, and may lead to underdiagnosis. The [...] Read more.
Background/Objectives: Arboviral diseases transmitted by Aedes mosquitoes, including Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), represent a major public health challenge in tropical regions. Their clinical similarity complicates differential diagnosis, particularly in settings of viral co-circulation, and may lead to underdiagnosis. The objective was to detect acute dengue infection and assess serological evidence of Chikungunya and Zika virus exposure among patients with acute febrile syndrome and clinical suspicion of dengue in the department of Córdoba, Colombia. Methods: A prospective descriptive study was conducted between 2023 and 2024 in healthcare institutions in Montería and Sahagún. Serum samples were analyzed by ELISA to detect DENV NS1 antigen, anti-CHIKV IgM, and anti-ZIKV IgG antibodies. Sociodemographic, clinical, and laboratory variables were described, and the association between prior ZIKV infection and dengue severity was assessed. Results: Ninety patients were included. Isolated laboratory marker detection was observed for DENV NS1 antigen in 36.7% (33/90), anti-ZIKV IgG in 30.0% (27/90), and anti-CHIKV IgM in 2.2% (2/90); combined arboviral markers were identified in 22.2% (20/90), and 8.9% (8/90) had no detectable markers. Among NS1-confirmed dengue cases (n = 47), 61.7% (29/47) were classified as dengue with warning signs. Anti-ZIKV IgG detection was not associated with dengue clinical classification (p = 0.989), although platelet counts were lower in IgG-positive cases (p = 0.037). Conclusions: The findings support laboratory-supported diagnosis and integrated acute febrile illness surveillance in Córdoba, including locally adapted vector control, in a setting of arbovirus co-circulation with overlapping laboratory markers. Full article
(This article belongs to the Section Vector-Borne Diseases)
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16 pages, 280 KB  
Review
Management of Periprosthetic Joint Infections: A Multidisciplinary Approach
by Madhan Jeyaraman, Filippo Migliorini, Luise Schäfer and Naveen Jeyaraman
Antibiotics 2026, 15(6), 614; https://doi.org/10.3390/antibiotics15060614 - 17 Jun 2026
Viewed by 607
Abstract
Periprosthetic joint infection (PJI) remains one of the most severe and complex complications following joint arthroplasty. With the global increase in primary hip and knee replacements, the clinical and economic burden associated with PJI continues to grow. Although relatively uncommon, PJI is linked [...] Read more.
Periprosthetic joint infection (PJI) remains one of the most severe and complex complications following joint arthroplasty. With the global increase in primary hip and knee replacements, the clinical and economic burden associated with PJI continues to grow. Although relatively uncommon, PJI is linked to substantial morbidity, elevated mortality, and significantly higher healthcare costs compared to aseptic revision procedures. The challenge is compounded by the intricate pathogenesis of biofilm-forming microorganisms, heterogeneous clinical presentations, and the lack of universally standardised diagnostic criteria. This review provides an integrated overview of current evidence concerning the pathophysiology, risk factors, and microbiological patterns associated with PJI. Contemporary diagnostic pathways based on the Musculoskeletal Infection Society/International Consensus Meeting (MSIS/ICM) criteria are summarised, including the utility and limitations of established serological markers, emerging synovial biomarkers such as alpha-defensin, and the complementary roles of culture techniques, histopathology, and molecular assays. Medical and surgical treatment strategies are outlined, including debridement with implant retention, one-stage and two-stage revision approaches, and organism-directed antimicrobial therapy. Preventive strategies spanning preoperative optimisation, intraoperative protocols, and postoperative risk reduction are also highlighted. Despite significant advances, important gaps persist, particularly in antimicrobial resistance, the management of polymicrobial or culture-negative infections, and the treatment of high-risk or immunocompromised patients. Continued interdisciplinary collaboration and high-quality clinical research are essential to refine diagnostic algorithms, improve therapeutic outcomes, and reduce the incidence of this increasingly consequential complication. Full article
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