Blood Advances

Allogeneic hematopoietic cell transplantation (allo-HCT) hinges on a delicate trade-off between graft-versus-tumor control and graft-versus-host disease (GvHD), mediated by donor T-cell recognition of antigens presented by recipient human leukocyte antigen (HLA) molecules. We hypothesized that, beyond allele-level matching, sequence divergence at peptide-binding grooves across donor and recipient HLA loci shapes these responses. To this end, we evaluated the effect of HLA evolutionary divergence...

ObjectivesThe therapeutic efficacy of rituximab has reduced the discriminatory power of the International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL), particularly within intermediate-risk categories. To address this "risk dilution," we aimed to develop and internally validate the AB-IPI (Albumin-BCL2 Refined Prognostic Index) using a hypothesis-driven approach that integrates tumor burden, host fitness, and tumor biology. MethodsThis multi-center retrospective study analyze...

T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates. Clonality testing is frequently required for diagnosis. It lacks the spatial context and is slow and expensive, relying on complex, multiplexed PCR reactions, interpreted by experienced scientists or pathologists. We previously published details of a pair of highly specific monoclonal antibodies against the two alternatively used, but very similar, T-cell receptor {beta} constant regions, TCR{beta}1 and T...

BackgroundSickle Cell Anaemia (SCA), a genetic blood disorder caused by a single mutation in the beta globin gene, displays a highly variable clinical course. Hydroxyurea (HU), an effective treatment, has an unclear mechanism of action. Plasma proteins can act as biomarkers for understanding disease states and response to HU treatment in SCA patients. MethodsPlasma proteome profiling of 31 healthy individuals and 76 SCA patients, including those with and without HU treatment, was performed usin...

A role for substance P in promoting neurogenic inflammation and pain has been described in sickle cell disease (SCD). However its origin and contribution to SCD pathophysiology remain unclear. We measured substance P level in plasma from 225 patients with SCD and observed the highest concentrations during acute chest syndrome (ACS). Therefore, we tested the hypothesis that substance P may induce ACS. In transgenic sickle mice, unlike control mice, intravenous injection of substance P caused leth...

ObjectivePost-thrombotic syndrome (PTS), a common complication of deep vein thrombosis, lacks objective diagnostic biomarkers and its molecular mechanisms remain poorly understood. This study aimed to identify plasma biomarkers and clarify pathways using integrated multi-omics and machine learning. MethodsProteomic and metabolomic profiling of 75 PTS patients and 75 controls was performed. Differential expression analysis, pathway enrichment, and protein-metabolite network analysis were conduct...

ObjectiveAutoimmune diseases (ADs) markedly elevate venous thromboembolism (VTE) risk, yet the shared genetic architecture and tissue-specific regulatory mechanisms of this "Autoimmune-Thrombotic Axis" remain poorly defined. We aimed to characterize the genomic landscape of immunothrombosis to identify causal links and therapeutic targets. Approach and ResultsWe integrated large-scale GWAS data for VTE and 16 ADs using a multi-omics framework, including pleiotropy scanning, local genetic correl...

Iron deficiency (ID) is the most common nutritional deficiency worldwide, often caused by insufficient dietary intakes. Oral supplementation is one of the means to improve iron status. This study evaluated the efficacy and safety of two low-dose iron supplements - >Your< Iron Forte Capsules (YIFC) and Ferrous Sulfate Capsules (FSC) - in individuals with dietary ID. One hundred and one participants (mean age 30.6 years; 98% women) with low iron stores (mean serum ferritin 16.1 {micro}g/L) were ra...

BackgroundAnthracyclines are central to childhood cancer therapy but predispose patients to cardiotoxicity leading to long-term cardiovascular risk. Endothelial injury and impaired repair contribute to this, yet pediatric data remain limited. ObjectiveTo longitudinally assess endothelial injury and repair in childhood cancer patients treated with anthracyclines by quantifying circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs). MethodsIn a single-centre retrospective c...

PurposeSepsis-associated immunothrombosis significantly contributes to high mortality, yet the role of N-glycosylation in this process remains poorly understood. This study aimed to comprehensively profile the plasma N-glycosylation landscape in sepsis and elucidate how its specific reprogramming in the complement and coagulation cascades influences immunothrombotic balance and patient outcomes. MethodsWe performed in-depth 4D-DIA proteomic and N-glycomic analyses on plasma from 43 sepsis patie...

Allogeneic hematopoietic cell transplantation is the only curative option for many patients with acute myeloid leukemia (AML). In the current study, we designed and implemented a personalized assay, called v96, incorporating up to 96 mutations in 30 AML patients undergoing transplantation. The assay was performed on DNA derived in cells from the bone marrow as well as in cell-free plasma. All 30 (100%) of patients harbored molecular evidence of residual leukemia during remission that was detecta...

BackgroundPediatric long COVID is associated with substantial symptom burden, yet evidence-based pharmacologic treatments remain limited. Low-dose naltrexone (LDN) has been proposed as a potential symptomatic therapy, but data in pediatric populations is lacking. MethodsWe conducted a retrospective analysis of pediatric and young adult patients ([&le;]25 years) with a clinical diagnosis of long COVID who were prescribed LDN between July 2020 and July 2025 at three multidisciplinary pediatric lo...

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and life-threatening complication of chimeric antigen receptor (CAR) T-cell therapy, with early detection being critical for timely intervention and improved outcomes. Cytokines such as interleukin-6 (IL-6) are key mediators of the inflammatory cascade underlying ICANS pathogenesis, but prospective clinical evidence for their predictive value is limited. Here we quantify IL-6 levels in a prospective cohort of 40 CAR-T pat...

Meningiomas are the most common primary brain tumors and, despite their benign reputation, often behave aggressively. Meningiomas are morphologically heterogeneous, yet the full significance of their histologic diversity is unclear. This is in large part because many features are not readily quantifiable by traditional observer-based light microscopy. Molecular testing improves prognostic stratification, but is not universally accessible. We therefore sought to determine whether an artificial in...

BackgroundIn lung transplantation, de novo immunodominant donor-specific anti-HLA antibodies recognizing HLA-DQ antigens (dn-iDSA-DQ) are predominant and can induce chronic lung allograft dysfunction (CLAD). We previously developed a method to measure the active concentration of dn-iDSA-DQ. We aimed to determine whether this new quantitative biomarker is associated with transplantation outcomes. MethodsThis retrospective multicentre cohort study included 90 lung transplant recipients (LTRs) dev...

BackgroundIron metabolism disorder is highly prevalent before and after heart transplantation (HTx). The impact of pretransplant and posttransplant iron disorder on posttransplant outcomes is unclear. ObjectivePretransplant serum levels of key regulator proteins of iron metabolism (hepcidin, interleukin-6, erythroferrone) were tested for prediction of the composite outcome 1-year posttransplant all-cause mortality (ACM) or [&ge;]moderate acute cellular rejection (ACR). Furthermore, serum levels...

Syphilis remains a major public health concern. However, current serologic assays are limited in their ability to distinguish active from previously treated disease. We applied tandem mass tag-based quantitative proteomics to plasma from 10 adults with active syphilis and 10 age- and gender-matched non-diseased controls. We identified 54 differentially regulated proteins (36 upregulated, 18 downregulated). Those proteins map to immune and inflammatory responses, acute-phase signaling, coagulatio...

POLE sequencing for somatic mutations (POLEmut) guides adjuvant therapy in endometrial cancer (EC), but cost and infrastructural considerations lead to limited uptake. Omission of POLE testing leads to unnecessary exposure to radiotherapy and/or chemotherapy. We developed POLARIX, a multiple instance deep learning model with attention pooling, which predicts POLE mutation status from routine hematoxylin and eosin whole-slide images (WSIs). Trained on 2,238 cases from eleven EC cohorts, POLARIX s...

Background & AimsPerihilar cholangiocarcinoma is an aggressive malignancy with clinical heterogeneity and poor long-term outcomes after resection. Current prognostic assessment relies mainly on anatomical staging and pathological features, which incompletely capture the entire postoperative risk. We aimed to determine whether integrative analysis of clinical, surgical, pathological and tumor genomic data could improve time-resolved, individualized recurrence-risk prediction after curative-intent...

ObjectiveTo explore the application value of dual-staining for specific AT sequence binding protein 2 (SATB2) immunohistochemistry and elastic lamina in detecting elastic lamina invasion (ELI) in pT3 colon cancer, and to assess its association with clinicopathological characteristics, staging, and prognosis. MethodsThis retrospective cohort study enrolled 176 pT3 colon cancer patients who underwent radical resection at Affiliated Jinhua Hospital Zhejiang University School of Medicine. The deepe...