The prevalence of celiac disease (CeD) in children with type 1 diabetes mellitus (T1DM) is significant, and celiac serology screening is routinely done in T1DM patients. The sequence of CeD and T1DM diagnosis and the natural history of transient celiac serology in T1DM is poorly defined. We aimed to investigate the temporal relationship between T1DM and CeD diagnoses, and the long-term natural history of celiac serology and CeD diagnosis in children with T1DM. A retrospective cohort study of 1,799 children with T1DM, treated at a single tertiary center (2009-2024), was evaluated for clinical, laboratory, and histologic data. Patients with positive anti-tissue-transglutaminase IgA antibodies (anti-TTG) were stratified based on CeD diagnosis or long-term serological behavior on a gluten-containing diet. Among 136 patients with T1DM and positive anti-TTG, 113 were diagnosed with CeD, 15 had persistent seropositivity (without confirmed CeD), and eight had a single borderline result (< ×3 upper limit of normal). CeD was diagnosed after T1DM in 81.4% of cases, and prior to TIDM in 18.6%. Patients diagnosed with CeD prior to T1DM exhibited more gastrointestinal symptoms, higher EMA positivity, and poorer glycemic control (p < 0.05). HbA1c values at follow-up were significantly higher in patients with CeD, compared to those with a single borderline anti-TTG, p < 0.01. In conclusion, most, but not all, patients with T1DM and elevated celiac serology, eventually develop biopsy-confirmed CeD. CeD can precede T1DM in a significant number of cases, emphasizing the need for continued monitoring for celiac serology in children diagnosed with T1DM and monitoring for developing T1DM in patients with CeD.

End-stage renal disease (ESRD) patients receiving maintenance hemodialysis are at high risk of hepatitis B virus (HBV) infection and demonstrate inadequate immune response to vaccination. The objective of the study was to assess the antibody response (anti-HBs levels) of hepatitis B vaccinated maintenance hemodialysis patients. This cross-sectional observational analytical study was conducted at Marine City Medical College Hospital, Chittagong, Bangladesh for 34 months of period among 50 patients receiving maintenance hemodialysis for more than 4 months. Demographic and clinical data were collected and post-vaccination anti-HBs titers were measured. Patients were classified as high responders (anti-HBs ≥100 mIU/ml), poor responders (anti-HBs ≥10 to <100 mIU/ml) and non-responders (anti-HBs <10 mIU/ml). The mean age of participants was 52±10 years; 60.0% were male. The mean duration of dialysis was 19.7±7.7 months. The common causes of ESRD were diabetic nephropathy (58.0%), glomerulonephritis (24.0%), hypertension (12.0%) and others (6.0%). Overall, 38.0% were high responders, 26.0% poor responders and 36.0% non-responders, seroconversion rate was 64.0%. Mean anti-HBs titers were 663±463 mIU/ml in high responders, 31.55±23.24 mIU/ml in poor responders and 3.23±1.98 mIU/ml in non-responders. Age >50 years, presence of diabetes mellitus and lower serum albumin were significantly associated with poor or non response (p<0.05). Development of protective antibody levels after hepatitis B vaccination in maintenance hemodialysis patients was inadequate. Older age, diabetes and low serum albumin were important predictors of poor response. Strategies such as booster dosing and revaccination may improve seroconversion rates in this population.

Preterm delivery is an important risk factor for child mortality and psychiatric, metabolic and cardiovascular disease later in life. In most of the cases, the cause of prematurity remains unidentified. There is still ongoing debate about whether abnormal maternal thyroid function during pregnancy contributes to a higher risk of preterm birth. This study aimed to examine the relationship between hypothyroidism, the presence of anti-thyroid antibodies and preterm delivery. This cross-sectional analytic study was conducted in the Department of Obstetrics and Gynaecology at Dhaka Medical College Hospital (DMCH), Bangladesh from June 2022 to May 2023. Two hundred patients were enrolled in this study obeying exclusion and inclusion criteria. Purposive sampling method was used for the selection of respondent. Both preterm and term labor was diagnosed clinically. Gestational age was established based on LMP and early dated ultrasonography. Estimation of maternal thyroid stimulating hormone (Serum TSH) was done by Immuno-radiometric assay and anti-thyroperoxidase antibody (Anti-TPO) by Siemens ADVIA Centaur XPT Chemiluminescence Immunoassay methods. Relevant data was collected in a predesigned questionnaire. Among women who experienced preterm delivery, 27.0% were found to have hypothyroidism, whereas only 12.0% of those who delivered at term had this condition. Anti-TPO antibody positivity was observed in 16.0% of the preterm group compared with 7.0% of the term delivery group. Both the prevalence of hypothyroidism and anti-TPO antibody positivity were significantly higher in the preterm delivery group, with the differences reaching statistical significance (p<0.05). But this significant association was with very early preterm group not with moderate preterm delivery. Hypothyroidism had effect on preterm delivery rates, but had significant association with very early preterm delivery. The existence of anti-TPO antibodies in the serum had a significant increasing effect on preterm deliveries and could be regarded as risk factor.

Protecting populations against pathogens that induce non-sterilizing immunity remains a major public health challenge. However, conventional mathematical models are often incompatible with within-host data, offering limited insight into how immune responses drive epidemics. To address this gap, we develop a modular, data-driven mathematical framework that links immunological and virological dynamics to population-level transmission. Our approach derives infectiousness from viral load and protection against reinfection from time-varying immune responses, allowing epidemic trajectories to emerge from the summation of individual-level processes. As an example, we use viral load quantified in a SARS-CoV-2 human challenge study and binding antibody levels post-vaccination against SARS-CoV-2. The framework captures individual-level infection dynamics and shows that immune responses fundamentally shape epidemic trajectories. We show that weak correlations between antibody levels and protection lead to frequent reinfections and endemic circulation, whereas strong correlations generate recurrent explosive outbreaks. We fit the model to simulated case data to demonstrate its ability to recover underlying protection and reinfection dynamics. Applied to real-world data, this framework could provide new insights into the drivers of epidemic patterns and inform vaccination strategies for pathogens with non-sterilizing immunity.

Anti-neutrophil cytoplasmic antibodies (ANCA) positivity is not uncommon among patients with interstitial lung disease(ILD), but its clinical significance and disease classification remain poorly defined. Some patients present only with pulmonary fibrosis and show no evidence of systemic vasculitis throughout long-term follow-up, whereas others gradually develop ANCA-associated vasculitis (AAV). Current classification systems generally place such cases in the categories of AAV-associated ILD, ANCA-positive ILD, or interstitial pneumonia with autoimmune features (IPAF). However, none of these categories adequately accounts for their marked clinical heterogeneity and dynamic evolution. Recent studies suggest that ANCA-associated interstitial lung involvement may represent a disease spectrum linking pulmonary fibrosis and systemic vasculitis rather than a discrete disease entity with well-defined boundaries. Drawing on relevant research advances, this commentary examines the challenges in classifying ANCA-positive ILD and reconsiders its clinical significance from the perspectives of disease spectrum and dynamic evolution. Such an approach may provide a more comprehensive framework for understanding its biological heterogeneity and clinical behavior.

A 52-year-old male patient presented with a 6-month history of cough and exertional dyspnea that had worsened over 2 days. Six months earlier, he had developed exertional dyspnea accompanied by a paroxysmal dry cough. At another hospital, anti-RNP/Sm and anti-Jo-1 antibodies were weakly positive, anti-Ku antibodies were positive, and the rheumatoid factor level was elevated. High-resolution computed tomography (HRCT) of the chest demonstrated pulmonary emphysema, honeycomb pattern in the lower lobes, scattered patchy ground-glass opacities and consolidations, as well as traction bronchiectasis. Bronchoalveolar lavage culture, tuberculosis-related investigations, and liquid-based cytology were all negative for pathogens and malignant cells. He was treated first with glucocorticoids and subsequently with glucocorticoids plus mycophenolate mofetil; however, follow-up chest CT revealed that the pulmonary lesions had increased in extent and density. Upon admission, physical examination revealed crackles bilaterally. Repeat autoantibody testing remained positive. Following multidisciplinary discussion, repeat bronchoscopy was performed, and a transbronchial lung biopsy established the diagnosis of pulmonary adenocarcinoma involving both lungs.

Epidermal growth factor receptor (EGFR), cellular mesenchymal-epithelial transition factor (c-MET), and B7 homolog 3 (B7H3) are important targets for antibody-based drug development in colorectal cancer (CRC). To overcome the limitations of single-target antibody therapies - such as limited efficacy, widespread resistance, narrow patient populations, and treatment-related toxicities - various bispecific antibodies or antibody-drug conjugate (ADCs) targeting two targets are being extensively validated in clinical settings. A deeper understanding of their expression profiles and co-expression patterns of actionable therapeutic targets may guide more effective treatment strategies. We evaluated the immunohistochemical expression of B7H3, c-MET, and EGFR in a cohort of 193 CRC patients. Among which, B7H3 exhibited the highest positivity rate (80.83%) in CRC tissues, followed by c-MET (77.20%) and EGFR (47.15%). The positive rates of B7H3 showed no significant differences across patient gender, age, TNM stage, differentiation grade, or tumor site. In contrast, the c-MET positivity rate was elevated in patients with stage I-II disease, and the expression of EGFR was significantly higher in female patients than in male patients. Concurrent assessment of the three targets in metastatic lesions revealed that B7H3 expression levels were comparable between primary and metastatic tumors, whereas c-MET expression was significantly higher in primary lesions. Co-expression analysis indicated that the group with the highest patient coverage was the B7H3/c-MET dual-positive group, followed by the B7H3/EGFR, and c-MET/EGFR combinations, and the proportion of patients with at least one positive target exceeded 80%. Finally, mRNA profile from TIMER database reveals that CD276 and MET expression in CRC tumor tissues were higher than those in the majority of normal tissues. Therefore, utilizing B7H3/c-MET combination therapies that integrate intracellular signaling inhibition with immune checkpoint modulation could potentially extend therapeutic benefits to a wider range of CRC patients.

Nimotuzumab is an anti-epidermal growth factor receptor antibody. This Phase I study evaluated the pharmacokinetics and safety of nimotuzumab plus irinotecan in Chinese patients with advanced solid tumors. At single ascending dosage (SAD) stage, four cohorts (100, 200, 400, and 600 mg) of patients received nimotuzumab intravenously on Day 1, alongside irinotecan 180 mg/m2 on Day 8. Three weeks later, all patients in the four cohorts transferred to multiple ascending dosage (MAD) stage: nimotuzumab was administrated weekly for 6 weeks, alongside irinotecan (Days 1, 15, 29, 43, and 57, 180 mg/m2). Primary objective was pharmacokinetics, safety and tolerability was also examined. From December 2012 to October 2014, in SAD and MAD stages, there were 28 and 39 patients with Stage IV solid tumors. The area under the concentration curve (AUC0-∞) for a single dose of nimotuzumab was 10.2 ± 2.7 (100 mg), 37.6 ± 10.0 (200 mg), 114.8 ± 35.5 (400 mg), 197.6 ± 32.0 (600 mg) (×100 h µg/mL), and for multiple dose, it was 26.7 ± 3.4 (100 mg), 87.1 ± 12.0 (200 mg), 193.4 ± 46.9 (400 mg) and 446.3 ± 100.7 (600 mg) (×100 h µg/mL). There was low incidence of rash and no dose-limiting toxicities occurred. This study indicated that nimotuzumab at doses ranging from 100 to 600 mg exhibited a manageable and tolerable safety profile.

REGN17092, a fully human immunoglobulin (Ig) G1 antibody with M252Y/S254T/T256E (YTE) modification in the Fc portion, was assessed in a first-in-human study (ClinicalTrials.gov, NCT05923424). REGN17092 was designed to target the severe acute respiratory coronavirus 2 (SARS-CoV-2) S protein. However, due to the emergence of new SARS-CoV-2 variants, the program was discontinued. In this single-center, randomized, placebo-controlled, single-ascending-dose study, participants received a single IV dose of REGN17092 (300, 1200, or 2400 mg) or placebo, or a single SC dose of REGN17092 (300 or 1200) or placebo. Endpoints assessed included pharmacokinetics (PK), safety, and immunogenicity. Allometric scaling was used to predict the terminal half-life of REGN17092 and to ensure adequate exposure multiples relative to the exposure at the NOAEL. Forty participants were included. Mean concentrations of REGN17092 in serum increased in a dose-proportional manner and were consistent with linear PK for a single dose administered IV or SC. PK analysis of a single dose of REGN17092 administered IV or SC suggests that REGN17092 has a half-life of 80-90 days and showed detectable penetration into nasal fluid. No anti-drug antibody responses were noted. In this Phase 1 study, REGN17092 was tolerable with a long half-life, highlighting the value of YTE modification.

A simultaneous pharmacokinetic (PK)/pharmacodynamic (PD) analysis was conducted to characterize relationships between anti-B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate, belantamab mafodotin, and longitudinal multiple myeloma (MM) disease markers (soluble BCMA [sBCMA], M-protein). Data from patients with relapsed/refractory MM receiving belantamab mafodotin monotherapy in the DREAMM-1 (NCT02064387), DREAMM-2 (NCT03525678), DREAMM-3 (NCT04162210), or DREAMM-5 (NCT04126200) trials were included. The dataset contained 510 patients with 15,860 PK and PD observations. Previous population PK and M-protein PD models were combined to create a new starting model. Overparameterization was reduced using sensitivity analyses to create a 2-compartment base model for belantamab mafodotin with a linear clearance component and target-mediated drug disposition assuming quasi-equilibrium between belantamab mafodotin and sBCMA binding. Free belantamab mafodotin affected M-protein elimination rate via a direct effect, and M-protein in turn scaled sBCMA synthesis rate. sBCMA was assumed to transfer into the central free sBCMA compartment through a reservoir compartment, allowing capture of observed differences in timescales. Stepwise covariate modeling led to the final model, which contained eight covariate effects (baseline sBCMA, albumin, body weight, and sex on belantamab mafodotin clearance; baseline body weight and sex on belantamab mafodotin central volume of distribution; extramedullary disease at screening and baseline sBCMA on M-protein death rate constant). Simulations of belantamab mafodotin doses/schedules showed concentrations of free sBCMA and M-protein decreased as free and total belantamab mafodotin increased with higher doses. The PKPD model captured the clearance of belantamab mafodotin and the highly dynamic interactions between belantamab mafodotin PK, M-protein, and sBCMA.

Respiratory syncytial virus (RSV) glycoprotein G is heavily glycosylated and of variable size following virus growth in transformed cell lines or primary cells. However, it is unknown if the cell culture medium can influence the patterns of glycosylation. Therefore, we tested whether the choice of culture medium can affect the glycosylation of RSV G protein, viral infectivity and antibody recognition. The RSV G ectodomain was produced in HEK293T cells cultured in three different media. Marked differences in molecular weight were observed that were abolished in glycosylation-deficient knockout cells. RSV produced in A549 cells cultured in the same media also differed in relative G protein signals in virus stocks and virus spread. Higher apparent G protein glycosylation was associated with lower binding signals of human F protein-specific monoclonal antibodies to RSV-infected cells. These data show that the cell culture medium can influence biological properties of RSV preparations with consequences for antibody recognition and viral spread.

The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis drives immune exclusion in pancreatic ductal adenocarcinoma (PDA). Building on our preclinical data, we conducted the first stage of an open-label, single-arm phase 2 clinical trial combining CXCR4 inhibition (motixafortide), PD-1 blockade (cemiplimab), and chemotherapy (gemcitabine/nab-paclitaxel [GN]; MCGN) in 11 treatment-naïve patients with metastatic PDA ( NCT04543071 ). The primary endpoint, objective response rate, was 64% partial response and 55% confirmed partial response per Response Evaluation Criteria in Solid Tumors. Secondary endpoints include median progression-free survival of 9.7 months (95% confidence interval [CI]: 5.9-not reached [NR]), overall survival of 10.1 months (95% CI: 9.3-NR), duration of response of 8.2 months, and 91% disease control rate. One patient achieved a pathological complete response after pancreatoduodenectomy and hepatectomy, remaining disease-free for 18 months without adjuvant therapy. Exploratory single-nucleus RNA-sequencing of serial biopsies showed reduced tumor heterogeneity, depletion of epithelial-to-mesenchymal transitional states, and enrichment of CXCL12+ cancer-associated fibroblasts in responders relative to resistant patients. MCGN also induced tumor inflammation as confirmed by tissue staining and T cell rescue. A multicenter randomized phase 2 trial comparing MCGN to GN in patients with treatment-naïve metastatic PDA is ongoing.