The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent 'structure and specificity features', and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
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http://dx.doi.org/10.1080/19420862.2020.1729683 | DOI Listing |
Neurol Neuroimmunol Neuroinflamm
May 2025
Department of Neurology, University Hospital of Marseille, France.
Background And Objectives: A simple, quick, and reproducible procedure for distinguishing multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD) at inaugural optic neuritis (ION) could be highly valuable in guiding early management.
Methods: We included all adults admitted to the MS center of Marseille for ION between March 2016 and April 2024, with CSF analysis including the kappa free light chain (K-FLC) index. Receiver operating characteristic curves were used to measure the diagnostic ability of the K-FLC index.
Cancer Rep (Hoboken)
March 2025
Department of Oncology, KU Leuven, Leuven, Belgium.
Background: CD19-directed chimeric antigen receptor T-cell therapy tisagenlecleucel has shown promising results in the treatment of pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, around 50% of patients relapse after tisagenlecleucel. Following multiple relapses, limited treatment options are left, and the prognosis is dismal.
View Article and Find Full Text PDFDaru
March 2025
Department of Pharmacy, Beijing Hospital; National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), No. 1 Dahua Road, Dongcheng District, Beijing, 100730, P.R. China.
Background: Rituximab (RTX) is one of the treatment options for refractory myasthenia gravis (MG), yet the optimal dosing schedule remains undetermined. Our study aims to explore this issue and offer a valuable reference for clinical dosing.
Methods: This is a single-arm meta-analysis.
Clin Exp Nephrol
March 2025
Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan.
Nephrotic syndrome is the most common glomerular disease in children, and various hypotheses regarding its etiology have been proposed, primarily focusing on immune-related mechanisms. Nephrotic syndrome can manifest as a monogenic disease caused by deleterious variants in genes such as NPHS1, which encodes nephrin. In steroid-sensitive nephrotic syndrome, HLA class II and immune-related genes have been identified as susceptibility genes.
View Article and Find Full Text PDFPurpose: To investigate the efficacy, safety, tolerability, and serum IgG trough levels of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in US pediatric patients with primary immunodeficiency diseases (PIDDs).
Methods: This phase 3, open-label, prospective study (NCT03277313) was conducted at 17 US centers. Eligible patients aged 2 to < 16 years had PIDDs and had received immunoglobulin G (IgG) at a consistent dose for ≥ 3 months before screening.
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