Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.045
Filter
1.
J Clin Med ; 13(17)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39274343

ABSTRACT

Background: In advanced head and neck cancer (HNC) patients, 50-60% experience loco-regional relapse and distant metastasis. Boron neutron capture therapy (BNCT) has shown remarkable therapeutic response in recurrent HNC, but there is still a 70% chance of local recurrence. This study aimed to identify a suitable liquid biomarker to assess patient response following BNCT. Myeloid-derived suppressor cells (MDSCs) are immune-suppressive cells that inhibit cytotoxic T cells. Circulating MDSC levels have been linked to the clinical stage and prognosis in HNSCC. Methods: Five patients with recurrent head and neck cancer underwent a treatment regimen that commenced with BNCT, followed by fractionated image-guided intensity-modulated radiotherapy (IG-IMRT). Liquid biopsy analysis via flow cytometry and tumor volume analysis by clinical imaging were conducted at three stages: before BNCT, before the first fraction of IG-IMRT, and one month after the last fraction of IG-IMRT. Results: Compared to other MDSC subtypes, monocytic MDSCs (M-MDSCs) exhibited a notable correlation with tumor volume. This strong correlation was observed at all testing time points except one month after BNCT treatment. Conclusions: This case series highlights a strong link between tumor size and circulating M-MDSC levels before BNCT and one month after the last IG-IMRT treatment in recurrent head and neck cancer patients. These results suggest that the level of circulating M-MDSCs could be a marker for monitoring tumor progression in recurrent HNC patients following radiation therapy, including BNCT.

2.
Stud Health Technol Inform ; 316: 1280-1284, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39176615

ABSTRACT

The Survivorship Passport (SurPass) for childhood cancer survivors provides a personalized treatment summary together with a care plan for long-term screening of possible late effects. HL7 FHIR connectivity of Electronic Health Record (EHR) systems with the SurPass has been proposed to reduce the burden of collecting and organizing the relevant information. We present the results of testing and validation efforts conducted across six clinics in Austria, Belgium, Germany, Italy, Lithuania, and Spain. We also discuss ways in which this experience can be used to reduce efforts for the SurPass integration in other clinics across Europe.


Subject(s)
Cancer Survivors , Electronic Health Records , Humans , Child , Europe , Health Level Seven , Neoplasms/therapy , Health Information Interoperability
3.
Front Immunol ; 15: 1442749, 2024.
Article in English | MEDLINE | ID: mdl-39206195

ABSTRACT

Background: Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. Our aims were to investigate whether the immunological phenotype of IgGsd patients on and off immunoglobulin replacement therapy (IgRT) was reflected in the clinical features of IgGsd. Method: Thirty patients with IgGsd were included in this prospective study of 18 months of IgRT, followed by 7-18 months of IgRT discontinuation. Blood samples were collected when patients were on and off IgRT and compared with samples from 34 cross-sectional healthy controls. An in-depth lymphocyte phenotyping was performed by flow cytometry and plasma levels of immune checkpoints were assessed. Results: IgG3 subclass deficiency was most common. Patients with IgGsd had decreased levels of activated T cells and B cells and plasma levels of negative immune checkpoint molecules correlated negatively with T cell and B cell activation. The decreased T cell activation level was unaffected by IgRT, while the B cell activation was partly restored. Of note, decreased levels of activated regulatory T cells (Tregs) were found in IgGsd patients and was partly restored during IgRT. The profile of comorbidities did not associate with Treg levels. Discussion: IgGsd is associated with decreased B cell and T cell activation including Tregs, and increased plasma levels of negative immune checkpoint molecules. The consequence of reduced activated Tregs in IgGsd remains unclear. Decreased immune cell activation was partly restored during IgRT, demonstrating that IgRT may contribute to improved immune function in patients with IgGsd.


Subject(s)
IgG Deficiency , Immunoglobulin G , Lymphocyte Activation , T-Lymphocytes, Regulatory , Humans , Male , Female , T-Lymphocytes, Regulatory/immunology , Middle Aged , Adult , IgG Deficiency/immunology , Lymphocyte Activation/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Cross-Sectional Studies , Prospective Studies , Aged , B-Lymphocytes/immunology , Immune Checkpoint Proteins/genetics , Immune Checkpoint Proteins/metabolism , Immunophenotyping , Immunoglobulins, Intravenous/therapeutic use
4.
Cell Rep Med ; 5(8): 101668, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39094579

ABSTRACT

We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Immunoglobulin G/immunology , Immunoglobulin G/blood , Humans , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , Epitopes/immunology , Female , Antibodies, Monoclonal/immunology , Male
5.
J Proteome Res ; 23(9): 3944-3957, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39146476

ABSTRACT

Solid organ transplant recipients with immunosuppressant regimens to prevent rejection are less able to mount effective immune responses to pathogenic infection. Here, we apply a recently reported mass spectrometry-based serological approach known as Ig-MS to characterize immune responses against infection with SARS-CoV-2 in cohorts of transplant recipients and immunocompetent controls, both at a single early time point following COVID-19 diagnosis as well as over the course of one-month postdiagnosis. We found that the antibody repertoires generated by transplant recipients against SARS-CoV-2 do not differ significantly compared to immunocompetent individuals with regard to repertoire titer, clonality, or glycan composition. Importantly, our study is the first to characterize the evolution of antibody glycan profiles in transplant recipients with COVID-19 disease, presenting evidence that the evolution of glycan composition in these immunocompromised individuals is similar to that in immunocompetent people.


Subject(s)
Antibodies, Viral , COVID-19 , Mass Spectrometry , SARS-CoV-2 , Transplant Recipients , Humans , COVID-19/immunology , COVID-19/virology , COVID-19/diagnosis , SARS-CoV-2/immunology , Antibodies, Viral/blood , Mass Spectrometry/methods , Immunocompromised Host , Middle Aged , Male , Female , Polysaccharides/immunology , Antibody Formation , Adult , Aged
6.
Front Oncol ; 14: 1457832, 2024.
Article in English | MEDLINE | ID: mdl-39144830

ABSTRACT

The incorporation of tyrosine kinase inhibitors (TKIs) in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) led to significant improvement. However, in the pediatric setting, the outcomes of Ph+ ALL are still inferior compared to those of other ALL subtypes even in the TKI era due to higher relapse rate. Herein, we report a very peculiar case of late extramedullary Ph+ ALL relapse in a child, characterized by lymphomatous presentation in the tonsils and lymphoid lineage switch. The diagnostic dilemma between the occurrence of a second malignant neoplasm and the recurrence of the primary disease is further discussed, highlighting the importance of molecular backtracking analysis. This case report emphasizes the high plasticity and polyclonal nature of ALL and expands the heterogeneity of possible clinical presentation of Ph+ ALL at relapse.

7.
Cureus ; 16(7): e65310, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39184637

ABSTRACT

INTRODUCTION:  Acute otitis externa is a localized inflammation of the skin of the external auditory meatus. It is characterized by pain, edema, erythema, and itchy discomfort. Treatment includes topical and oral antibiotics, analgesics, steroids, and anti-inflammatory medication for the ear. Aural medicated wicks are used to reduce edema and pain. AIM: To compare the clinical outcome of hydroxylated polyvinyl acetate ichthammol glycerine wick versus cotton ichthammol glycerine wick used in the treatment of acute otitis externa. MATERIALS AND METHODS: It is a six-month observational study with 120 patients. The patients in this study were grouped into two groups with hydroxylated polyvinyl acetate and cotton wick, respectively. Pain was assessed using the VAS score before and after three days of treatment of acute otitis externa. RESULT: Group B (patient treated with cotton ichthammol glycerine wick) had significant improvement in the pain score on days 2 and 3 compared to group A, with a significant p-value of <0.001. CONCLUSION:  During the second visit (on day 2), the cotton ear wick was significantly better in terms of otalgia when compared with the hydroxylated polyvinyl acetate. The cotton wick group showed better and faster recovery in terms of pain and edema compared to the polyvinyl alcohol (PVA) groups.

8.
Dev Comp Immunol ; 160: 105234, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39069110

ABSTRACT

Mink are susceptible to viruses such as SARS-CoV-2, H1N1 and H9N2, so they are considered a potential animal model for studying human viral infections. Therefore, it is important to study the immune system of mink. Immunoglobulin (Ig) is an important component of humoral immunity and plays an important role in the body's immune defense. In this study, we described the gene loci structure of mink Ig germline by genome comparison, and analysed the mechanism of expression diversity of mink antibody library by 5'RACE and next-generation sequencing (NGS). The results were as follows: the IgH, Igκ and Igλ loci of mink were located on chromosome 13, chromosome 8 and chromosome 3, respectively, and they had 25, 36 and 7 V genes, 3, 5 and 7 J genes and 10 DH genes, respectively. Mink Ig heavy chain preferred the IGHV1, IGHD2 and IGHJ4 subgroups, κ chain mainly use the IGKV1, IGKJ1 and IGHL4 subgroups, and λ chain mainly use the IGLV3 and IGLJ3 subgroups. Linkage diversity analysis revealed that N nucleotide insertion was the main factor affecting the linkage diversity of mink Igs. On the mutation types of mink Ig Somatic Hypermutation (SHM), the high mutation types of heavy chain were mainly G > A, C > T, T > C, A > G, C > A, G > T, A > C, and T > G; the high mutation types of κ chain were G > A and T > C; and the high mutation types of λ chain were G > A and A > G. The objective of this study was to analyse the loci structure and expression diversity of Ig in mink. The results contribute to our comprehension of Ig expression patterns in mink and were valuable for advancing knowledge in mink immunogenetics, exploring the evolution of adaptive immune systems across different species, and conducting comparative genomics research.


Subject(s)
Mink , Animals , Mink/genetics , Mink/immunology , High-Throughput Nucleotide Sequencing , Immunity, Humoral/genetics , COVID-19/immunology , COVID-19/virology , Immunoglobulins/genetics , Humans , Mutation/genetics , Immunoglobulin Heavy Chains/genetics , SARS-CoV-2/immunology , Genetic Loci
9.
Adv Exp Med Biol ; 1445: 37-46, 2024.
Article in English | MEDLINE | ID: mdl-38967748

ABSTRACT

It is widely acknowledged that immunoglobulins (Igs) are produced solely by B-lineage cells. The Ig gene is created by the rearrangement of a group of gene segments [variable (V), diversity (D), and joining (J) segments rearrangement, or V(D)J recombination], which results in the vast diversity of B cell-derived Ig responsible for recognising various antigens. Ig subsequently undergoes somatic hypermutation (SHM) and class switch recombination (CSR) after exposure to antigens, thus converting the low-affinity IgM to IgG, IgA, or IgE antibodies. IgM and IgD are primarily expressed in naïve B cells that have not been exposed to antigens, they do not undergo somatic hypermutation; hence, their variable region sequences remain the same as those in the germline. In contrast, IgG, IgA, and IgE are expressed in antigen-stimulated memory B cells or plasma cells, and thus, they often possess high-frequency mutations in their variable region sequences. Since the discovery that Ig can be produced by non-B cells, Qiu's group has investigated and compared the genetic characteristics of B cell-derived Ig and non-B cell-derived Ig. These findings demonstrated that non-B cell-derived Ig shares certain similarities with B cell-derived Ig in that the sequence of its constant region is identical to that of B cell-derived Ig, and its variable region is also strictly dependent on the rearrangement of V, D, and J gene segments. Moreover, akin to B cell-derived Ig, the V regions of IgM and IgD are rarely mutated, while IgG, IgA, and IgE produced by cancer cells are frequently mutated. However, the non-B cell-derived Ig V region sequence displays unique characteristics. (1) Unlike the vast diversity of B cell-derived Igs, non-B cell-derived Igs exhibit restricted diversity; cells from the same lineage always select the same V(D)J recombination patterns; (2) Both mRNA and proteins of RAG1/RAG2 recombinase have been detected in Ig positive cancer cell lines and normal tissues. But Ig recombination could also be found in RAG1-/- and RAG2-/- mice, suggesting that they are not necessary for the rearrangement of non-B cell-derived Igs. These features of non-B cell-derived Igs suggest a potentially undiscovered mechanism of V(D)J recombination, ligation, and SHM in non-B cells, which necessitates further investigation with advanced technology in molecular biology.


Subject(s)
B-Lymphocytes , Genes, Immunoglobulin , Animals , Humans , Mice , B-Lymphocytes/immunology , Genes, Immunoglobulin/genetics , Immunoglobulin Class Switching/genetics , Immunoglobulin Class Switching/immunology , Immunoglobulins/genetics , Immunoglobulins/immunology , Somatic Hypermutation, Immunoglobulin/genetics
10.
BMC Genomics ; 25(1): 663, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961347

ABSTRACT

BACKGROUND: The Atlantic cod is a prolific species in the Atlantic, despite its inconsistent specific antibody response. It presents a peculiar case within vertebrate immunology due to its distinct immune system, characterized by the absence of MHCII antigen presentation pathway, required for T cell-dependent antibody responses. Thorough characterisation of immunoglobulin loci and analysis of the antibody repertoire is necessary to further our understanding of the Atlantic cod's immune response on a molecular level. RESULTS: A comprehensive search of the cod genome (gadmor3.0) identified the complete set of IgH genes organized into three sequential translocons on chromosome 2, while IgL genes were located on chromosomes 2 and 5. The Atlantic cod displayed a moderate germline V gene diversity, comprising four V gene families for both IgH and IgL, each with distinct chromosomal locations and organizational structures. 5'RACE sequencing revealed a diverse range of heavy chain CDR3 sequences and relatively limited CDR3 diversity in light chains. The analysis highlighted a differential impact of V-gene germline CDR3 length on receptor CDR3 length between heavy and light chains, underlining different recombination processes. CONCLUSIONS: This study reveals that the Atlantic cod, despite its inconsistent antibody response, maintains a level of immunoglobulin diversity comparable to other fish species. The findings suggest that the extensive recent duplications of kappa light chain genes do not result in increased repertoire diversity. This research provides a comprehensive view of the Atlantic cod's immunoglobulin gene organization and repertoire, necessary for future studies of antibody responses at the molecular level.


Subject(s)
Gadus morhua , High-Throughput Nucleotide Sequencing , Animals , Gadus morhua/genetics , Immunoglobulin Heavy Chains/genetics , Immunoglobulins/genetics , Genetic Loci , Genes, Immunoglobulin , Immunoglobulin Variable Region/genetics
11.
Adv Exp Med Biol ; 1445: 47-57, 2024.
Article in English | MEDLINE | ID: mdl-38967749

ABSTRACT

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.


Subject(s)
Gene Expression Regulation , Immunoglobulins , Transcription, Genetic , Humans , Animals , Immunoglobulins/genetics , Immunoglobulins/metabolism , Gene Rearrangement , B-Lymphocytes/metabolism , B-Lymphocytes/immunology
12.
Adv Exp Med Biol ; 1445: 73-88, 2024.
Article in English | MEDLINE | ID: mdl-38967751

ABSTRACT

Immunoglobulin (Ig) has been widely acknowledged to be produced solely by B-lineage cells. However, growing evidence has demonstrated the expression of Ig in an array of cancer cells, as well as normal cells including epithelial cells, epidermal cells, mesangial cells, monocytes, and neutrophils. Ig has even been found to be expressed in non-B cells at immune-privileged sites such as neurons and spermatogenic cells. Despite these non-B cell-derived Igs (non-B-Igs) sharing the same symmetric structures with conventional Igs (B-Igs), further studies have revealed unique characteristics of non-B-Ig, such as restricted variable region and aberrant glycosylation. Moreover, non-B-Ig exhibits properties of promoting malignant behaviours of cancer cells, therefore it could be utilised in the clinic as a potential therapeutic biomarker or target. The elucidation of the generation and regulation of non-B-Ig will certainly broaden our understanding of immunology.


Subject(s)
Immunoglobulins , Humans , Animals , Immunoglobulins/genetics , Immunoglobulins/metabolism , Immunoglobulins/immunology , Glycosylation , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Neoplasms/immunology , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism
13.
Adv Exp Med Biol ; 1445: 119-128, 2024.
Article in English | MEDLINE | ID: mdl-38967754

ABSTRACT

Immunoglobulins (Igs) have been widely accepted to be exclusively expressed by B cells. Nonetheless, this theory is challenged by mounting evidence which suggests that Igs can also be generated by non B cells (non B-Ig), including cardiomyocytes (CM). Non B-Ig exhibits unique physical and chemical characteristics, unique variable region sequences and functions, which diverge from those of B-Ig. For instance, non B-Ig demonstrates hydrophobicity, limited diversity in the variable region, and extracellular matrix protein activity. Likewise, cardiomyocytes can express different classes of Igs, including IgM, IgG, and free Igκ light chains (cardiomyocyte derived-Igs, CM-Igs). In particular, CM-Igs can be secreted into the extracellular space in various cardiovascular diseases, such as myocardial ischaemia and myocardial fibrosis where they might be involved in complement activation and direct damage to cardiomyocytes. Nevertheless, the precise pathological activity of CM-Igs remains unclear. Recently, Zhu et al. focused on studying the sequence characteristics and functions of CM-Igκ; they discovered that the CM-Igκ exhibits a unique VJ recombination pattern, high hydrophobicity, and is principally located on the intercalated discs and cross striations of the cardiomyocytes. Interestingly, loss of Igκ in cardiomyocytes results in structural disorders in intercalated discs and dysfunction in myocardial contraction and conduction. Mechanically, Igκ promotes the stabilisation of plectin, a cytoskeleton cross-linker protein that connects desmin to desomsome, to maintain the normal structure of the intercalated disc. This finding indicates that CM-Igκ plays an integral role in maintaining cytoskeleton structure. Consequently, it is imperative to reveal the physiological functions and mechanisms of pathological injury associated with CM-Igs.


Subject(s)
Immunoglobulins , Myocytes, Cardiac , Humans , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Animals , Immunoglobulins/metabolism , Immunoglobulins/genetics , Clinical Relevance
14.
Adv Exp Med Biol ; 1445: 137-149, 2024.
Article in English | MEDLINE | ID: mdl-38967756

ABSTRACT

Intestinal epithelium constitutes a barrier to the unrestricted movement of pathogens, and other detrimental substances from the external world (gut lumen) into the interstitial environment. Intestinal epithelial cells obstruct harmful substances passing through the epithelium as a physical and chemical barrier; Moreover, the epithelial cells can express Toll-like receptors (TLRs) and cytokines to exert innate immune function. In addition, high levels of immunoglobulin A (IgA) and other antibodies exist in the intestinal mucosa, maintaining intestinal immune homeostasis in conjunction with intestinal probiotics. Traditionally, these antibodies have been deemed to be secreted by submucosal plasma cells. Nonetheless, in recent years, it has been demonstrated that intestinal epithelial cells produce a substantial amount of Igs, especially IgA or free Ig light chains, which are involved in intestinal immune homeostasis and the survival of normal epithelial cells. Furthermore, mounting evidence affirms that many human carcinoma cells, including colorectal cancer (CRC), can overexpress Igs, particularly IgG. Cancer-derived Igs exhibit a unique V(D)J rearrangement pattern distinct from B cell-derived Ig; moreover, this cancer cell-derived IgG also has a unique sialic acid modification on the 162 site of CH1 domain (SIA-IgG). The SIA-IgG plays a crucial role in promoting cancer initiation, progression, metastasis, and tumour immune escape. Simultaneously, CRC cells can also express free Ig light chains, which promote colitis, colitis-associated colon carcinogenesis, and CRC progression. Therefore, Igs expressed by CRC cells could be a potential target for diagnosing and preventing the transformation of inflammation into cancer, as well as treating CRC.


Subject(s)
Intestinal Mucosa , Humans , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Animals , Immunoglobulins/immunology , Immunoglobulins/metabolism , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology
15.
Adv Exp Med Biol ; 1445: 151-156, 2024.
Article in English | MEDLINE | ID: mdl-38967757

ABSTRACT

Skin is the most prominent tissue and organ, as well as the first line of defence, of the body. Because it is situated on the body's surface, it is constantly exposed to microbial, chemical, and physical factors such as mechanical stimulation. Therefore, skin has evolved substantial immune defences, regenerative ability, and anti-injury capacity. Epidermal cells produce antibacterial peptides that play a role in immune defence under physiological conditions. Additionally, IgG or IgA in the skin also participates in local anti-infective immunity. However, based on the classical theory of immunology, Ig can only be produced by B cells which should be derived from local B cells. This year, thanks to the discovery of Ig derived from non B cells (non B-Ig), Ig has also been found to be expressed in epidermal cells and contributes to immune defence. Epidermal cell-derived IgG and IgA have been demonstrated to have potential antibody activity by binding to pathogens. However, these epidermal cell-derived Igs show different microbial binding characteristics. For instance, IgG binds to Staphylococcus aureus and IgA binds to Staphylococcus epidermidis. Epidermal cells producing IgG and IgA may serve as an effective defense mechanism alongside B cells, providing a novel insight into skin immunity.


Subject(s)
Immunoglobulin A , Skin , Humans , Immunoglobulin A/immunology , Immunoglobulin A/metabolism , Skin/immunology , Animals , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , B-Lymphocytes/immunology , Immunoglobulins/immunology , Immunoglobulins/metabolism , Staphylococcus aureus/immunology , Staphylococcus epidermidis/immunology , Epidermis/immunology , Epidermis/metabolism , Epidermal Cells/immunology , Epidermal Cells/metabolism
16.
Genes (Basel) ; 15(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39062635

ABSTRACT

In humans, the HS1.2 enhancer in the Ig heavy-chain locus is modular, with length polymorphism. Previous studies have shown the following features for this variation: (i) strong population structuring; (ii) association with autoimmune diseases; and (iii) association with developmental changes in Ig expression. The HS1.2 region could then be considered as a contributor to inter-individual diversity in humoral response in adaptive immunity. We experimentally determined the HS1.2-length class genotype in 72 of the 1000 Genomes CEU cell lines and assigned the HS1.2 alleles to haplotypes defined by 18 landmark SNPs. We also sequenced the variable portion and ~200 bp of the flanking DNA of 34 HS1.2 alleles. Furthermore, we computationally explored the ability of different allelic arrangements to bind transcription factors. Non-random association between HS1.2 and Gm allotypes in the European population clearly emerged. We show a wealth of variation in the modular composition of HS1.2, with five SNPs further contributing to diversity. Longer alleles offer more potential sites for binding but, for same-length alleles, SNP variation creates/destroys potential binding sites. Altogether, the arrangements of modules and SNP alleles both inside and outside HS1.2 denote an organization of diversity far from randomness. In the context of the strong divergence of human populations for this genomic region and the reported disease associations, our results suggest that selective forces shaped the pattern of its diversity.


Subject(s)
Enhancer Elements, Genetic , Polymorphism, Single Nucleotide , Humans , Enhancer Elements, Genetic/genetics , Alleles , Haplotypes , Genome, Human , Transcription Factors/genetics , Binding Sites
17.
J Cell Mol Med ; 28(14): e18575, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39048916

ABSTRACT

In recent years, in the development of emerging immunotherapy, B7-H3 is also termed as CD276 and has become a novel chimeric antigen receptor (CAR)-T target against glioma and other tumours, and aroused extensive attention. However, B7-H3 has three isoforms (2, 3 and 4Ig) with the controversial expression and elusive function in tumour especially glioma. The current study mainly focuses on the regulatory factors and related mechanisms of generation of different B7-H3 isoforms. First, we have determined that 2Ig is dominant in glioma with high malignancy, and 4Ig is widely expressed, whereas 3Ig shows negative expression in all glioma. Next, we have further found that RNA binding protein annexin A2 (ANXA2) is essential for B7-H3 isoform maintenance, but fail to determine the choice of 4Ig or 2Ig. RNA methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and 5-methylcytosine reader Y-box binding protein 1 (YBX1) facilitate the production of 2Ig. Our findings have uncovered a series of factors (ANXA2/NSUN2/YBX1) that can determine the alternative generation of different isoforms of B7-H3 in glioma. Our result aims to help peers gain a clearer understanding of the expression and regulatory mechanisms of B7H3 in tumour patients, and to provide better strategies for designing B7H3 as a target in immunotherapy.


Subject(s)
Annexin A2 , B7 Antigens , Gene Expression Regulation, Neoplastic , Glioma , Protein Isoforms , Humans , Glioma/genetics , Glioma/metabolism , Glioma/pathology , B7 Antigens/metabolism , B7 Antigens/genetics , Protein Isoforms/metabolism , Protein Isoforms/genetics , Annexin A2/metabolism , Annexin A2/genetics , Cell Line, Tumor , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/pathology
18.
Adv Exp Med Biol ; 1445: 59-71, 2024.
Article in English | MEDLINE | ID: mdl-38967750

ABSTRACT

According to classical immunology theory, immunoglobulin (Ig) is exclusively produced by differentiated B lymphocytes, which exhibit a typical tetrapeptide chain structure and are predominantly present on the surface of B cells and in bodily fluids. B-Ig is one of the critical effector molecules for humoral immune responses specifically recognising antigens and eliminating them. However, mounting evidence has demonstrated that Ig is widely expressed in non B lineage cells, especially malignant ones (referred to as non B-Ig). Interestingly, non B-Ig mainly resides in the cytoplasm and secretion, but to some extent on the cell surface. Furthermore non B-Ig not only displays a tetrapeptide chain structure but also shows free heavy chains and free light chains (FLCs). Additionally, Ig derived from non B cancer cell typically displays unique glycosylation modifications. Functionally, non B-Ig demonstrated diversity and versatility, showing antibody activity and cellular biological activity, such as promoting cell proliferation and survival, and it is implicated in cancer progression and some immune-related diseases, such as renal diseases.


Subject(s)
B-Lymphocytes , Humans , Animals , Glycosylation , B-Lymphocytes/immunology , Immunoglobulins/immunology , Immunoglobulins/metabolism , Immunoglobulins/chemistry , Neoplasms/immunology , Neoplasms/pathology , Immunoglobulin Light Chains/chemistry , Immunoglobulin Light Chains/immunology , Immunoglobulin Light Chains/metabolism
19.
Sci Rep ; 14(1): 15226, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956271

ABSTRACT

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.


Subject(s)
Abatacept , Antirheumatic Agents , Arthritis, Rheumatoid , Interleukin-6 , Tumor Necrosis Factor Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Female , Male , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , Middle Aged , Abatacept/therapeutic use , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/pharmacology , Tumor Necrosis Factor Inhibitors/therapeutic use , Aged , Knee Joint/diagnostic imaging , Knee Joint/pathology , Knee Joint/drug effects , Adult , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/pharmacology , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors
20.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 608-635, jul. 2024. tab, ilus, graf, mapas
Article in English | LILACS | ID: biblio-1538071

ABSTRACT

Chile has two certified origin olive products: Extra-Virgin Olive Oil (EVOO) from Huasco valley and the Azapa variety table olive from the Azapa valley. However, efficient methodologies are needed to determine the varieties and raw materials involved in the end products. In this study, we assessed the size of alleles from ten microsatellites in 20 EVOOs and in leaves and fruits of 16 olive varieties cultivated in Chile to authenticate their origins. The identification of varieties relied on specific allele sizes derived from microsatellites markers UDO99-011 and DCA18-M found in leaves and fruit mesocarp. While most Chilean single-variety EVOOs matched the variety declared on the label, inconsistencies were observed in single-variety EVOOs containing multiple varieties. Our findings confirm that microsatellites serve as a valuable as diagnostic tools for ensuring the quality control of Geographical Indication certification for Azapa olives and EVOO with Designation of Origin from Huasco.


Chile cuenta con dos productos de oliva de origen certificado: El aceite de oliva virgen extra (AOVE) del valle del Huasco y la aceituna de mesa de la variedad Azapa del valle de Azapa. Sin embargo, se necesitan metodologías eficientes para determinar las variedades y materias primas involucradas en los productos finales. En este estudio, evaluamos el tamaño de los alelos de diez microsatélites en 20 AOVEs y en hojas y frutos de 16 variedades de aceituna cultivadas en Chile para autentificar sus orígenes. La identificación de las variedades se basó en los tamaños alélicos específicos derivados de los marcadores microsatélites UDO99-011 y DCA18-M encontrados en las hojas y el mesocarpio de los frutos. Aunque la mayoría de los AOVEs chilenos monovarietales coincidían con la variedad declarada en la etiqueta, se observaron incoherencias en los AOVEs monovarietales que contenían múltiples variedades. Nuestros hallazgos confirman que los microsatélites sirven como valiosas herramientas de diagnóstico para asegurar el control de calidad de la certificación de Indicación Geográfica para aceitunas de Azapa y AOVE con Denominación de Origen de Huasco.


Subject(s)
Plant Extracts/genetics , Microsatellite Repeats , Olea/genetics , Olive Oil/chemistry , Geography , Chile
SELECTION OF CITATIONS
SEARCH DETAIL