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Current Oncology (Toronto, Ont.) May 2022Immunoproliferative small intestinal disease (IPSID) is an uncommon disease with a higher prevalence in the developing world. IPSID diagnosis relies mainly on a tissue... (Review)
Review
Immunoproliferative small intestinal disease (IPSID) is an uncommon disease with a higher prevalence in the developing world. IPSID diagnosis relies mainly on a tissue biopsy and a high index of suspicion. Treatment options are variable; however, they mainly include anthracycline-based chemotherapy with or without antibiotics in advanced stages. Because of the paucity of IPSID, our perception of the disease remains narrow, and investigating the optimal lines of therapy and prevention without a complete comprehension of the disease is challenging. In our review, we explore the expansion of knowledge about IPSID, which has been developing over the years, to help increase the detection of IPISD cases and further research the most appropriate lines of therapy and prevention.
Topics: Biopsy; Humans; Immunoproliferative Small Intestinal Disease
PubMed: 35621691
DOI: 10.3390/curroncol29050301 -
The Journal of Clinical Investigation Apr 2023The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad...
The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.
Topics: Animals; Cricetinae; SARS-CoV-2; COVID-19; Antibodies; Epitopes; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 36862518
DOI: 10.1172/JCI166844 -
Current Topics in Microbiology and... 2015Immunoglobulin (Ig) E is the most tightly regulated of all Ig heavy chain (IgH) isotypes and plays a key role in atopic disease. The gene encoding for IgH in mature B... (Review)
Review
Immunoglobulin (Ig) E is the most tightly regulated of all Ig heavy chain (IgH) isotypes and plays a key role in atopic disease. The gene encoding for IgH in mature B cells consists of a variable region exon-assembled from component gene segments via V(D)J recombination during early B cell development-upstream of a set of IgH constant region CH exons. Upon activation by antigen in peripheral lymphoid organs, B cells can undergo IgH class switch recombination (CSR), a process in which the initially expressed IgH μ constant region exons (Cμ) are deleted and replaced by one of several sets of downstream CH exons (e.g., Cγ, Cε, and Cα). Activation of the IL-4 receptor on B cells, together with other signals, can lead to the replacement of Cμ with Cε resulting in CSR to IgE through a series of molecular events involving irreversible remodeling of the IgH locus. Here, we discuss the molecular mechanisms of CSR and the unique features surrounding the generation of IgE-producing B cells.
Topics: Animals; Humans; Immunoglobulin Class Switching; Immunoglobulin E; Immunoglobulin Heavy Chains; Transcription, Genetic
PubMed: 25553793
DOI: 10.1007/978-3-319-13725-4_2 -
Frontiers in Immunology 2021Heritability of Spondyloarthritis (SpA) is highlighted by several familial studies and a high association with the presence of human leukocyte antigen (HLA)-B27. Though... (Review)
Review
Heritability of Spondyloarthritis (SpA) is highlighted by several familial studies and a high association with the presence of human leukocyte antigen (HLA)-B27. Though it has been over four decades since the association of HLA-B27 with SpA was first determined, the pathophysiological roles played by specific HLA-B27 allotypes are not fully understood. Popular hypotheses include the presentation of arthritogenic peptides, triggering of endoplasmic reticulum (ER) stress by misfolded HLA-B27, and the interaction between free heavy chains or heavy chain homodimers of HLA-B27 and immune receptors to drive IL-17 responses. Several non-HLA susceptibility loci have also been identified for SpA, including endoplasmic reticulum aminopeptidases (ERAP) and those related to the IL-23/IL-17 axes. In this review, we summarize clinical aspects of SpA including known characteristics of gut inflammation, enthesitis and new bone formation and the existing models for understanding the association of HLA-B27 with disease pathogenesis. We also examine newer insights into the biology of HLA class I (HLA-I) proteins and their implications for expanding our understanding of HLA-B27 contributions to SpA pathogenesis.
Topics: Endoplasmic Reticulum Stress; HLA-B27 Antigen; Humans; Interleukin-17; Interleukin-23; Spondylitis, Ankylosing
PubMed: 33763060
DOI: 10.3389/fimmu.2021.601518 -
Journal of Hematology & Oncology Sep 2020The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with... (Review)
Review
The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer methods using next-generation sequencing, such as ClonoSeq, are being incorporated in clinical trials. Other techniques under evolution include CAPP-seq and anchored multiplex polymerase chain reaction-based methods. This review article aims to provide a comprehensive update on the status of minimal residual disease detection and its prognostic effect in mantle cell patients. The role of circulating tumor DNA-based minimal residual disease detection in lymphomas is also discussed.
Topics: Biomarkers, Tumor; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; DNA, Neoplasm; Flow Cytometry; Forecasting; Gene Rearrangement, B-Lymphocyte, Heavy Chain; High-Throughput Nucleotide Sequencing; Humans; Immunoglobulin Heavy Chains; Liquid Biopsy; Lymphoma, Mantle-Cell; Multiplex Polymerase Chain Reaction; Neoplasm, Residual; Prognosis; Translocation, Genetic
PubMed: 32972438
DOI: 10.1186/s13045-020-00961-8 -
American Journal of Kidney Diseases :... May 2024Light and heavy chain deposition disease (LHCDD) is a rare form of monoclonal immunoglobulin deposition disease (MIDD), and limited clinical data are available...
RATIONALE & OBJECTIVE
Light and heavy chain deposition disease (LHCDD) is a rare form of monoclonal immunoglobulin deposition disease (MIDD), and limited clinical data are available characterizing this condition. We described the clinicopathological characteristics and outcomes of LHCDD.
STUDY DESIGN
Case series.
SETTING & PARTICIPANTS
13 patients with biopsy-proven LHCDD, diagnosed between January 2008 to December 2022, at two Chinese medical centers.
FINDINGS
Among the 13 patients described, 6 were men and 7 were women, with a mean age of 52.6 ± 8.0 years. Patients presented with hypertension (76.9%), anemia (84.6%), elevated serum creatinine (84.6%, median serum creatinine 1.7 mg/dL), proteinuria (100%, average urine protein 3.0g/24h), nephrotic syndrome (30.8%) and microscopic hematuria (76.9%). Serum immunofixation electrophoresis showed monoclonal immunoglobulin for 11 (84.6%) patients. Serum free light chain (FLC) ratios were abnormal in 11 (84.6%) patients, and heavy/light chain (HLC) ratios were abnormal in 9 of 10 (90%) patients with available data. Five patients were diagnosed with multiple myeloma. A histological diagnosis of nodular mesangial sclerosis was made in 10 (76.9%) patients. Immunofluorescence demonstrated deposits of IgG subclass (γ-κ/γ-λ:4/3) in 7 patients, and IgA (α-κ/α-λ:2/3) in 5 patients. Six patients underwent IgG subclass staining (γ1/γ2/γ3:3/2/1). The deposits of IgD-κ were confirmed by mass spectrometry in 1 patient. Among 12 patients for whom data were available over a median of 26.5 months, 11 received chemotherapy, and 1 received conservative treatment. One patient died. Three (25%) patients progressed to kidney failure. Among the 9 patients evaluable for hematological and kidney disease progression, five (56%) had a hematologic response and one (11%) achieved improvement in kidney disease.
LIMITATIONS
Retrospective descriptive study, limited number of patients, UPEP or UIFE missing for most patients.
CONCLUSIONS
In this case series of LHCDD, light and heavy chain deposition in kidney tissues were most frequent with monoclonal IgG1-κ. Among patients with evaluable data, more than half had hematologic response but a kidney response was uncommon.
PubMed: 38750878
DOI: 10.1053/j.ajkd.2024.03.021 -
Frontiers in Immunology 2018Discussion of the antibody repertoire usually emphasizes diversity, but a conspicuous feature of the light chain repertoire is its lack of diversity. The diversity of... (Review)
Review
Discussion of the antibody repertoire usually emphasizes diversity, but a conspicuous feature of the light chain repertoire is its lack of diversity. The diversity of reported allelic variants of germline light chain genes is also limited, even in well-studied species. In this review, the implications of this lack of diversity are considered. We explore germline and rearranged light chain genes in a variety of species, with a particular focus on human and mouse genes. The importance of the number, organization and orientation of the genes for the control of repertoire development is discussed, and we consider how primary rearrangements and receptor editing together shape the expressed light chain repertoire. The resulting repertoire is dominated by just a handful of IGKV and IGLV genes. It has been hypothesized that an important function of the light chain is to guard against self-reactivity, and the role of secondary rearrangements in this process could explain the genomic organization of the light chain genes. It could also explain why the light chain repertoire is so limited. Heavy and light chain genes may have co-evolved to ensure that suitable light chain partners are usually available for each heavy chain that forms early in B cell development. We suggest that the co-evolved loci of the house mouse often became separated during the inbreeding of laboratory mice, resulting in new pairings of loci that are derived from different sub-species of the house mouse. A resulting vulnerability to self-reactivity could explain at least some mouse models of autoimmune disease.
Topics: Animals; Antibodies; Gene Rearrangement; Genes, Immunoglobulin Light Chain; Genetic Variation; Immunoglobulin Light Chains; Mice, Inbred Strains; Receptors, Immunologic; Self Tolerance; Species Specificity
PubMed: 30349529
DOI: 10.3389/fimmu.2018.02249 -
International Reviews of Immunology Jan 2018Camelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen-binding units to occur in nature. VHHs possess high degrees of solubility and robustness... (Review)
Review
Camelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen-binding units to occur in nature. VHHs possess high degrees of solubility and robustness enabling generation of multivalent constructs with increased avidity - characteristics that mark their superiority to other antibody fragments and monoclonal antibodies. Capable of effectively binding to molecular targets inaccessible to classical immunotherapeutic agents and easily produced in microbial culture, VHHs are considered promising tools for pharmaceutical biotechnology. With the aim to demonstrate the perspective and potential of VHHs for the development of prophylactic and therapeutic drugs to target diseases caused by bacterial and viral infections, this review article will initially describe the structural features that underlie the unique properties of VHHs and explain the methods currently used for the selection and recombinant production of pathogen-specific VHHs, and then thoroughly summarize the experimental findings of five distinct studies that employed VHHs as inhibitors of host-pathogen interactions or neutralizers of infectious agents. Past and recent studies suggest the potential of camelid heavy-chain variable domains as a novel modality of immunotherapeutic drugs and a promising alternative to monoclonal antibodies. VHHs demonstrate the ability to interfere with bacterial pathogenesis by preventing adhesion to host tissue and sequestering disease-causing bacterial toxins. To protect from viral infections, VHHs may be employed as inhibitors of viral entry by binding to viral coat proteins or blocking interactions with cell-surface receptors. The implementation of VHHs as immunotherapeutic agents for infectious diseases is of considerable potential and set to contribute to public health in the near future.
Topics: Animals; Bacterial Infections; Camelidae; Dental Caries; Diarrhea; Escherichia coli Infections; Humans; Immunization, Passive; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Lipopolysaccharides; Poliomyelitis; Recombinant Proteins; Respiratory Syncytial Virus Infections; Streptococcus mutans; Virus Diseases
PubMed: 29182399
DOI: 10.1080/08830185.2017.1397657 -
Diagnostic Pathology Aug 2022Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The... (Review)
Review
BACKGROUND
Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood.
CASE PRESENTATION
We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum.
CONCLUSIONS
Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia.
Topics: Heavy Chain Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis; Lymphoma; Mutation; Myeloid Differentiation Factor 88; Waldenstrom Macroglobulinemia
PubMed: 35932039
DOI: 10.1186/s13000-022-01244-1 -
Methods in Molecular Biology (Clifton,... 2017Multiple myeloma is a heterogeneous disease. Its chromosomal abnormalities have been extensively studied with a view to accurate prognostication and personalized... (Review)
Review
Multiple myeloma is a heterogeneous disease. Its chromosomal abnormalities have been extensively studied with a view to accurate prognostication and personalized therapy. Here, we describe the techniques commonly employed for elucidating chromosomal aberrations, prognostic impact of recurrent chromosomal abnormalities, and recently updated risk stratification systems.
Topics: Chromosome Aberrations; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Humans; In Situ Hybridization, Fluorescence; Interphase; Molecular Targeted Therapy; Multiple Myeloma; Neoplasm Staging; Polyploidy; Prognosis; Risk; Translocation, Genetic
PubMed: 27910031
DOI: 10.1007/978-1-4939-6703-2_23