Search Results (216)

Therapeutic antibodies have revolutionized hematology, offering targeted and effective treatments for both malignant and non-malignant diseases. In hematologic malignancies, anti-CD20, anti-CD19, anti-CD38, and anti–B-cell maturation antigen (BCMA) antibodies have markedly improved survival outcomes, whereas antibody–drug conjugates and bispecific antibodies continue to expand therapeutic possibilities. Besides cancer, complement inhibitors such as eculizumab, ravulizumab, and the recently approved crovalimab have redefined paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome management, and the bispecific antibody emicizumab has transformed prophylaxis in hemophilia A. Furthermore, novel antibody formats such as the trifunctional anti-CD38 × CD3 antibody (Tri-31C2) exhibit enhanced anti-myeloma activity compared to chimeric CD38 antibodies, underscoring the future potential of T-cell–redirecting designs. This review summarizes key developments in therapeutic antibodies for hematological disorders, their action mechanisms, and emerging strategies to further optimize their efficacy and safety. Full article

Shiga toxin-producing Escherichia coli (STEC) is a major foodborne pathogen, responsible for severe gastrointestinal disease and hemolytic uremic syndrome (HUS). Here, we report Click Detect, a novel diagnostic platform that leverages click display to efficiently produce sensing probes for sandwich-style antigen detection. Click display is an in vitro protein display technology that generates uniform and covalently linked protein–cDNA conjugates in a simple one-pot reaction format within 2 h. The captured sensing probe can be quantified by standard nucleic acid amplification assays. Using click displayed DARPin (D_#20) as the sensing probe and a high-affinity nanobody (N_G1) as the capture reagent, Click Detect reliably detected Shiga toxin 2 (Stx2) at 600 fM by quantitative PCR (qPCR) and 6 pM by loop-mediated isothermal amplification (LAMP). The assay maintained comparable sensitivity in matrices containing up to 40% public swimming pool water or lettuce extract, highlighting robustness for real-world surveillance applications. Key advantages of Click Detect include simple, rapid, and cost-effective (~USD 0.04 per assay) sensing probe preparation, as well as a versatile plug-and-play probe format for detecting other targets. We believe that Click Detect has great potential as a novel sensing platform for food/environmental monitoring and point-of-care diagnostics, with potentially broad applicability to other toxins and protein targets. Full article

Background/Objectives: Hemolytic uremic syndrome is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Liver involvement in pediatric hemolytic uremic syndrome is increasingly recognized, but its clinical significance remains unclear. This study aimed to evaluate the relationship between liver involvement and clinical outcomes in children with hemolytic uremic syndrome. Methods: We retrospectively analyzed 25 pediatric patients diagnosed with hemolytic uremic syndrome. Patients were grouped based on liver involvement, defined by elevated transaminase levels. Demographic, clinical, laboratory, and treatment data were collected. Associations between liver involvement, intensive care unit admission, dialysis, plasma exchange, and length of intensive care unit stay were assessed using statistical analyses. Results: Liver involvement was observed in 68% of patients. Although liver involvement was not associated with the need for dialysis, affected patients required plasma exchange and intensive care unit admission significantly more often. An AST cutoff of ≥42 U/L moderately predicted adverse outcomes (AUC: 0.619), while ALT had limited prognostic value (AUC: 0.658). Transaminase levels normalized within a mean of 3.76 ± 1.92 days. No mortality was observed in our cohort, in contrast to previously reported rates of 2–5%. Conclusions: Liver involvement in pediatric hemolytic uremic syndrome is common but generally follows a reversible and benign course. While it is associated with increased intensive care unit admission and plasma exchange, it does not independently predict disease severity. These findings emphasize the importance of supportive management and suggest that liver involvement should be interpreted in the context of the overall clinical picture. Full article

The Shiga toxin-producing strain of Escherichia coli with serotype O157:H7 can cause acute bloody diarrhea, which can lead to life-threatening hemolytic uremic syndrome. According to the World Health Organization, this bacterium causes 2.8 million cases annually. Therefore, this theoretical study based on molecular docking and dynamics examined the inhibitory capacity of a series of aza-heterocyclic derivatives against the effector protein NleL of enterohemorrhagic E. coli (PDB ID: 3NAW), by determining affinity energy, stability, H-bond interactions and binding free energies of the compounds. The results obtained have enabled the identification of compounds with the potential to inhibit this infectious strain, contributing to an understanding of this protein. Full article

Microbial growth in food represents a public health problem that requires immediate attention. In Ecuador, 8924 cases of foodborne illness (FBD) were reported in 2020, most of them caused by bacteria. It is estimated that Escherichia coli causes 2,801,000 acute illnesses per year and results in 3890 cases of hemolytic uremic syndrome, 270 cases of end-stage renal disease and 230 deaths. Under this context, in this work, alginate capsules containing bioactive compounds from Lactobacillus plantarum GP108 were developed and their antimicrobial effect against E.coli was measured. The formulation of the capsules was carried out using a completely randomized experimental design with three formulations: maximum, average and minimum. The antimicrobial activity was measured by in vitro tests based on the increase in optical density during 7 days of exposure of E. coli with the capsules. By analysis of variance (ANOVA), it was found that the percentage inhibition of the capsules depended only on the formulation (p-value < 0.05), but not on the number of exposure capsules (p-value > 0.05). Tukey’s test indicated that the average formulation is the best at inhibiting the growth of E. coli, maintaining an average of 11.66% inhibition for 7 days. These findings show that bioactive compounds produced by L. plantarum GP108 encapsulated in alginate could be of potential use for food biopreservation. Full article

Background: Pregnancy-Related Acute kidney injury (PRAKI) is a critical complication of pregnancy, defined by the sudden deterioration in renal function during gestation or within the initial six weeks postpartum. Pregnancy is thought to increase the risk of acute kidney injury (AKI) by 51%. This is linked to the anatomical alterations that occur during pregnancy and special conditions, such as preeclampsia/eclampsia. PRAKI’s epidemiology and outcome vary between developed and developing nations. PRAKI is an uncommon entity in high-income countries; however, its incidence has recently increased. The aim of this systematic review is to evaluate the maternal and perinatal outcomes and risk factors affecting pregnancies affected by AKI. Methods: Comprehensive research was performed in PubMed/Medline, Scopus, and Google Scholar electronic databases from 2015 up to January 2025, using the terms AKI, PRAKI, sepsis, preeclampsia/eclampsia, liver enzymes, low platelet count (HELLP) syndrome, and pregnancy. After a thorough assessment, 25 full-text articles were obtained. Results: Our results revealed that preeclampsia, eclampsia, HELLP syndrome, and antepartum and postpartum hemorrhage predispose women to PRAKI. Other unusual factors, like disseminated intravascular coagulation (DIC) or hemolytic uremic syndrome (HUS), should not be underestimated. Furthermore, the latest published data showed unfavorable maternal and fetal outcomes in pregnancies affected by AKI compared to the general population. Conclusions: PRAKI constitutes a serious pregnancy complication that requires immediate treatment. The higher prevalence of PRAKI in developing countries (4–26%) versus wealthy nations (1.0–2.8%) has considerably indicated the impact of socioeconomic status and the accessibility of health services. Full article

Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred in Europe, resulting in symptoms ranging from bloody diarrhea to life-threatening colitis and hemolytic uremic syndrome (HUS). Since treatment options remain limited and have changed little over the past 40 years, there is an urgent need for an effective vaccine. Such a vaccine would offer major public health and economic benefits by preventing severe infections and reducing outbreak-related costs. A multiepitope vaccine approach, enabled by advances in immunoinformatics, offers a promising strategy for targeting HUS-causing E. coli (O104:H4 and O157:H7 serotypes) with minimal disruption to normal microbiota. This study aimed to design an immunogenic multiepitope vaccine (MEV) construct using bioinformatics and immunoinformatic tools. Methods and Results: Comparative proteomic analysis identified 672 proteins unique to E. coli O104:H4, excluding proteins shared with the nonpathogenic E. coli K-12-MG1655 strain and those shorter than 100 amino acids. Subcellular localization (P-SORTb) identified 17 extracellular or outer membrane proteins. Four proteins were selected as vaccine candidates based on transmembrane domains (TMHMM), antigenicity (VaxiJen), and conservation among EHEC strains. Epitope prediction revealed ten B-cell, four cytotoxic T-cell, and three helper T-cell epitopes. Four MEVs with different adjuvants were designed and assessed for solubility, stability, and antigenicity. Structural refinement (GALAXY) and docking studies confirmed strong interaction with Toll-Like Receptor 4 (TLR4). In silico immune simulations (C-ImmSim) indicated robust humoral and cellular immune responses. In Conclusions, the proposed MEV construct demonstrated promising immunogenicity and warrants further validation in experimental models. Full article

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article

Background/Objectives: The field of nephrology is increasingly embracing advanced treatments and clinical trials that focus on inhibiting specific components of the complement cascade, a key driver in complement-mediated kidney diseases. Materials and Methods: This review aims to summarize innovative therapies targeting various pathways, including the inhibition of the terminal part of the complement pathway (mainly C5), the alternative pathway (factor B inhibitors), and the lectin pathway (MASP inhibitors. C5 inhibitors play a critical role in preventing the formation of the membrane attack complex (MAC), offering effective solutions for conditions like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G). Results: A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases. Conclusions: Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases. Full article

Complement system inhibitors are emerging as promising therapies in nephrology, particularly for diseases where complement dysregulation is central to pathogenesis. This review summarizes the role of complement activation in kidney diseases and current evidence supporting complement-targeted treatments. As the complement system can be involved in the pathogenesis of different diseases to varying degrees, several research works have been conducted. These research efforts aim, firstly, to understand the mechanisms and role of complement cascade components in the most prevalent nephrological diseases and, secondly, to explore the potential of complement system inhibitors in these conditions and their possible clinical applications. Clinical trials demonstrate that complement inhibitors are most effective in conditions with significant complement involvement, such as C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These agents show variable benefits in diseases with partial complement activation, including lupus nephritis and ANCA-associated vasculitis, while their role in disorders like diabetic nephropathy and focal–segmental glomerulosclerosis remains limited. Complement inhibition offers a targeted strategy to prevent disease progression and improve outcomes in selected nephrological disorders. Full article

There is rapidly increasing evidence of the role of complement in different forms of kidney disease and this has broadened the field to involve not only atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G), but also a number of other glomerular diseases, mainly ANCA-associated renal vasculitis, immune-complex glomerulonephritis, membranous nephropathy, and IgA nephropathy (IgAN). In parallel, the field of therapeutic agents able to target the three complement pathways at different levels, both proximally and terminally, has grown tremendously in recent years. This has led to the approval of agents targeting complement for ANCA-associated vasculitis, IgA nephropathy, and, very recently, C3 glomerulopathy. The real-world implementation of these agents remains a challenge. This review will attempt, through the presentation of representative clinical vignettes, to provide some practical guidance for the nephrologist in how to navigate these new therapeutic opportunities, focusing on aHUS, C3G, and IgAN. Full article

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing Escherichia coli-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease. Full article

Background: Enterohemorrhagic Escherichia coli (EHEC) is a considerable public health concern associated with several foodborne outbreaks of bloody diarrhea (BD) and the potentially lethal hemolytic uremic syndrome (HUS), the pathophysiology of which is attributable to the Shiga toxin (Stx) produced by this bacterium. In most patients, supportive treatment will be sufficient; however, in some cases, antibiotic treatment may be necessary. Most antibiotics are not recommended for EHEC infection treatment, particularly those that kill the bacteria, since this triggers the release of Stx in the body, inducing or worsening HUS. Azithromycin, which prevents the release of Stx and is a weaker inducer of the SOS system, has been successfully used to reduce EHEC shedding. It is necessary to identify compounds that eliminate EHEC without inducing Stx release. The use of natural compounds such as curcumin (CUR), a polyphenol derived from turmeric, has been highlighted as an alternative bactericidal treatment approach. Objective: The objective of this study was to establish the effect of CUR and its interactions with selected antibiotics on resistant EHEC O157/H7/EDL933. Methods: Bacterial cultures were exposed to CUR at three different concentrations (110, 220, and 330 µg/mL) and 1.2% DMSO, and the antimicrobial activity of CUR was assessed by measuring the optical density at 600 nm (OD600). The synergy of CUR and the antibiotics was determined with the FIC method. RT-PCR was performed to determine the expression levels of the bla_CTX-M-15, catA1, acrAB-tolC stx2A, and stx2B genes. Results: Our data indicate that CUR did not affect the growth of EHEC, but when combined with the antibiotics, it acted as a bacterial resistance breaker. Synergistic combinations of CUR and cefotaxime or chloramphenicol significantly reduced colony counts. Conclusions: Our findings support the potential of CUR as a sensitizer or in combination therapy against EHEC. Full article

Background: Atypical hemolytic uremic syndrome (HUS) is a rare form of thrombotic microangiopathy (TMA) characterized by complement dysregulation. Cocaine use has been reported to be a potential trigger of TMA; however, the underlying mechanisms remain poorly elucidated. Proposed hypotheses include direct endothelial injury, activation of the complement cascade, and the unmasking of whether HUS is genetic or acquired. Case Report: We report the case of a 47-year-old man who presented with hypertensive emergency and acute kidney injury following intranasal cocaine use. The laboratory findings were consistent with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and markedly elevated lactate dehydrogenase (LDH) levels. Renal biopsy (RB) revealed classic features of TMA, including glomerular capillary thrombosis, fibrinoid necrosis, and acute tubular injury. Complement studies demonstrated reduced levels of Factor I, indicative of complement dysregulation. The patient was treated with therapeutic plasma exchange and four weekly doses of eculizumab, resulting in hematologic remission and significant improvement in renal function, without the need for dialysis. Genetic testing for known atypical HUS-associated mutations was negative; therefore, maintenance therapy with eculizumab was discontinued without clinical relapses. Discussion: This case underscores cocaine as a rare but important precipitating factor for atypical HUS in predisposed individuals. Early diagnosis, RB, and complement evaluation were essential in determining the etiology and guiding targeted therapy. Complement inhibition with eculizumab was effective in halting disease progression and preventing long-term renal damage. Conclusions: This case highlights the relevance of considering cocaine use as a potential trigger of complement-mediated TMA. Early identification of aHUS features and prompt initiation of complement inhibition therapy may be critical to preventing irreversible kidney injury. Full article

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen that causes a variety of diseases, ranging from self-limiting gastroenteritis to life-threatening extra-intestinal diseases such as hemolytic uremic syndrome. EspF, an effector protein secreted by the type III secretion system of EHEC, is primarily responsible for the development of inflammatory colitis. Our previous study revealed that EspF interacts with the host Annexin A6 (ANXA6) protein and targets the endoplasmic reticulum (ER). Given the critical effects of ER stress on the host responses of gastroenteritis, we explored the role of EspF–ANXA6 interaction in ER stress. Caco-2 cells were infected with different strains of EHEC and transfected with modified plasmids to establish in vitro research models. Our results revealed that infection with espF-deletion EHEC strains significantly exacerbated ER stress. Specifically, the phosphorylation of eIF2α was elevated, and the expression levels of BiP, ATF4, and CHOP were increased by more than 15% compared to those in cells infected with wild-type EHEC strains. Further experiments showed that EspF co-localizes with BiP and down-regulates the PERK pathway. Meanwhile, the EspF–ANXA6 interaction could aggravate the inhibition of the PERK pathway and stimulate calcium influx to disturb ER homeostasis, eventually leading to apoptosis. Our findings suggest that the EspF–ANXA6 interaction could inhibit ER stress through the PERK pathway, which may limit cell-to-cell communication and block the clearance of bacteria in host cells. Full article