Serum protein electrophoresis revealed a monoclonal gammopathy in three patients who presented with glomerulonephritis. Other features of myeloma were not found. Clinical manifestations of glomerulonephritis included marked proteinuria and significant hematuria. Rate of progression of renal failure was variable. Morphologically, glomerulonephritis was characterized by diffuse proliferative lesion with predominant mesangial involvement. Immunoglobulins and complement were found deposited in the mesangium. Immunoglobulins deposited in the glomeruli were found to consist exclusively of the circulating monoclonal IgG in one patient. Immunoglobulins eluted from the glomeruli of another patient consisted of immunoglobulin (IgM) which had electrophoretic mobility similar to that of the monoclonal spike in the serum. Selective deposition of monoclonal immunoglobulins in the glomeruli indicated that an active process was involved in their glomerular localization and that the monoclonal immunoglobulins may have had a role in the pathogenesis of glomerulonephritis in these patients.
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http://dx.doi.org/10.1016/0002-9343(77)90828-2 | DOI Listing |
Sci Immunol
January 2025
Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical HPAI H5 hemagglutinin (HA), the major target of antibody responses.
View Article and Find Full Text PDFEur J Immunol
January 2025
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
P2X7 is an extracellular adenosine 5'-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2 antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown.
View Article and Find Full Text PDFClin Transl Gastroenterol
January 2025
Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.
Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.
Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.
Cancer
February 2025
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.
Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.
J Neurol
January 2025
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Introduction: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).
Methods: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.
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