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2.
Trends Immunol ; 45(3): 167-176, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38402044

RESUMO

Antibody-coding genes accumulate somatic mutations to achieve antibody affinity maturation. Genetic dissection using various mouse models has shown that intrinsic hypermutations occur preferentially and are predisposed in the DNA region encoding antigen-contacting residues. The molecular basis of nonrandom/preferential mutations is a long-sought question in the field. Here, we summarize recent findings on how single-strand (ss)DNA flexibility facilitates activation-induced cytidine deaminase (AID) activity and fine-tunes the mutation rates at a mesoscale within the antibody variable domain exon. We propose that antibody coding sequences are selected based on mutability during the evolution of adaptive immunity and that DNA mechanics play a noncoding role in the genome. The mechanics code may also determine other cellular DNA metabolism processes, which awaits future investigation.


Assuntos
Genes de Imunoglobulinas , Hipermutação Somática de Imunoglobulina , Animais , Camundongos , Hipermutação Somática de Imunoglobulina/genética , Mutação , DNA , Citidina Desaminase/genética , Citidina Desaminase/metabolismo
3.
Rheumatology (Oxford) ; 63(1): 218-225, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37137278

RESUMO

OBJECTIVES: Approximately 20% of people with psoriasis develop PsA. Although genetic, clinical and environmental risk factors have been identified, it is not known why some people with psoriasis develop PsA. The skin disease is traditionally considered the same in both. This study compares transcriptional changes in psoriasis and PsA skin for the first time. METHODS: Skin biopsies were collected from healthy controls (HC), and uninvolved and lesional skin from patients with PsA. Bulk tissue sequencing was performed and analysed using the pipeline Searchlight 2.0. Transcriptional changes in PsA skin were compared with existing sequencing data from participants with psoriasis without PsA (GSE121212). Psoriasis and PsA datasets could not be directly compared as different analysis methods were used. Data from participants with PsA in the GSE121212 dataset were used for validation. RESULTS: Skin samples from 9 participants with PsA and 9 HC were sequenced, analysed and compared with available transcriptomic data for 16 participants with psoriasis compared with 16 HC. Uninvolved skin in psoriasis shared transcriptional changes with lesional skin in psoriasis, but uninvolved skin in PsA did not. Most transcriptional changes in psoriasis and PsA lesional skin were shared, but immunoglobulin genes were upregulated in PsA lesional skin specifically. The transcription factor POU2F1, which regulates immunoglobulin gene expression, was enriched in PsA lesional skin. This was confirmed in the validation cohort. CONCLUSIONS: Immunoglobulin genes are upregulated in PsA but not in psoriasis skin lesions. This may have implications for the spread from the cutaneous compartment to other tissues.


Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/patologia , Genes de Imunoglobulinas , Psoríase/metabolismo , Pele/patologia , Regulação da Expressão Gênica
5.
J Immunol ; 211(11): 1613-1622, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983521

RESUMO

Effective Ab-mediated responses depend on a highly diverse Ab repertoire with the ability to bind a wide range of epitopes in disease-causing agents. The generation of this repertoire depends on the somatic recombination of the variable (V), diversity (D), and joining (J) genes in the Ig loci of developing B cells. It has been known for some time that individual V, D, and J gene segments rearrange at different frequencies, but the mechanisms behind this unequal V gene usage have not been well understood. However, recent work has revealed that newly described enhancers scattered throughout the V gene-containing portion of the Ig loci regulate the V gene recombination frequency in a regional manner. Deletion of three of these enhancers revealed that these elements exert many layers of control during V(D)J recombination, including long-range chromatin interactions, epigenetic milieu, chromatin accessibility, and compartmentalization.


Assuntos
Cromatina , Região Variável de Imunoglobulina , Cromatina/genética , Região Variável de Imunoglobulina/genética , Rearranjo Gênico/genética , Genes de Imunoglobulinas/genética , Receptores de Antígenos de Linfócitos B/genética
6.
Nat Commun ; 14(1): 7468, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978187

RESUMO

While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL) has been reported, the contribution of light chain loci (IGK/IGL) remains elusive. This study is to evaluate the prognosis of IGH and IGK/IGL rearrangement-based MRD detected by next-generation sequencing in B-ALL at the end of induction (EOI) and end of consolidation (EOC). IGK/IGL rearrangements identify 5.5% of patients without trackable IGH clones. Concordance rates for IGH and IGK/IGL are 79.9% (cutoff 0.01%) at EOI and 81.0% (cutoff 0.0001%) at EOC, respectively. Patients with NGS-MRD < 0.01% at EOI or <0.0001% at EOC present excellent outcome, with 3-year event-free survival rates higher than 95%. IGH-MRD is prognostic at EOI/EOC, while IGK-MRD at EOI/EOC and IGL-MRD at EOI are not. At EOI, NGS identifies 26.2% of higher risk patients whose MRD < 0.01% by flow cytometry. However, analyzing IGK/IGL along with IGH fails to identify additional higher risk patients both at EOI and at EOC. In conclusion, IGH is crucial for MRD monitoring while IGK and IGL have relatively limited value.


Assuntos
Genes de Imunoglobulinas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sequenciamento de Nucleotídeos em Larga Escala
7.
J Med Virol ; 95(10): e29179, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37877800

RESUMO

Although monoclonal antibodies to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are known, B-cell receptor repertoire and its change in patients during coronavirus disease-2019 (COVID-19) progression is underreported. We aimed to study this molecularly. We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naïve and extrafollicular B cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B cells at various time points during COVID-19 progression.


Assuntos
COVID-19 , Genes de Imunoglobulinas , Humanos , COVID-19/genética , SARS-CoV-2/genética , Receptores de Antígenos de Linfócitos B/genética , Linfócitos B , Anticorpos Antivirais
8.
Nat Commun ; 14(1): 6601, 2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857610

RESUMO

Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.


Assuntos
Genoma , Genômica , Bovinos , Animais , Genoma/genética , Complexo Principal de Histocompatibilidade/genética , Imunoglobulinas , Genes de Imunoglobulinas
9.
J Exp Med ; 220(11)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37824081

RESUMO

Several species generate their preimmune repertoire in gut-associated lymphoid tissues (GALT), compensating a reduced germline V gene repertoire by post-rearrangement diversification mechanisms (gene conversion and/or somatic hypermutation) in these environments that act as primary lymphoid organs. We summarize here these processes for three different species (chickens, sheep, and rabbits) and further discuss the analogous process that T-independent B cell responses in humans represent: we indeed recently showed that response against bacterial polysaccharides mobilize marginal zone B cells that prediversified against gut antigens. While the initial diversification strategy differs in these two cases, i.e., repertoire formation driven by gut-derived mitotic signals vs. response against gut antigens, the common feature of these two processes is the mobilization of a B cell compartment prediversified in GALT for immune responses against distinct systemic antigens.


Assuntos
Diversidade de Anticorpos , Genes de Imunoglobulinas , Humanos , Animais , Coelhos , Ovinos/genética , Galinhas/genética , Linfócitos B , Tecido Linfoide
10.
Methods Mol Biol ; 2702: 77-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37679616

RESUMO

Recombinant antibody libraries based on chicken immunoglobulin genes are potentially valuable sources of phage-displayed scFvs for use in veterinary diagnostics and research. To add diversity to the scFv repertoire, we expanded the library to include genes from the ostrich, indigenous to southern Africa. The libraries described in this chapter are based on the chicken and ostrich variable heavy and light chain immunoglobulin genes joined by a short flexible linker cloned in the phagemid vector pHEN1. The resulting phagemids produce either scFvs displayed on the surface of the fusion phage subsequent to co-infection with helper phage or soluble scFvs following IPTG induction. This chapter provides detailed and proven methods for the construction of such libraries.


Assuntos
Struthioniformes , Animais , Galinhas , Anticorpos , Cadeias Leves de Imunoglobulina , Genes de Imunoglobulinas
11.
Methods Mol Biol ; 2702: 347-372, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37679629

RESUMO

Antibody libraries came into existence 30 years ago when the accumulating sequence data of immunoglobulin genes and the advent of PCR technology made it possible to clone antibody gene repertoires. Phage display (most common) and additional display and screening technologies were applied to pan out desired binding specificities from antibody libraries. As other antibody discovery tools, phage display is not an off-the-shelf technology and not offered as a kit but rather requires experience and expertise for making it indeed very useful.Next-generation sequencing (NGS) coupled with bioinformatics is a powerful tool for analyzing large amount of DNA sequence output of the panning. Here, we demonstrate how NGS analysis of phage biopanning (phage-Seq) of complex antibody libraries can facilitate the antibody discovery process and provide insights regarding the biopanning process (see Fig. 1).


Assuntos
Bacteriófagos , Anticorpos de Cadeia Única , Humanos , Anticorpos de Cadeia Única/genética , Genes de Imunoglobulinas , Sequenciamento de Nucleotídeos em Larga Escala , Bioprospecção
12.
Cell Rep Methods ; 3(9): 100570, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37751688

RESUMO

Reprogramming somatic cells into pluripotent stem cells (iPSCs) enables the study of systems in vitro. To increase the throughput of reprogramming, we present induction of pluripotency from pooled cells (iPPC)-an efficient, scalable, and reliable reprogramming procedure. Using our deconvolution algorithm that employs pooled sequencing of single-nucleotide polymorphisms (SNPs), we accurately estimated individual donor proportions of the pooled iPSCs. With iPPC, we concurrently reprogrammed over one hundred donor lymphoblastoid cell lines (LCLs) into iPSCs and found strong correlations of individual donors' reprogramming ability across multiple experiments. Individual donors' reprogramming ability remains consistent across both same-day replicates and multiple experimental runs, and the expression of certain immunoglobulin precursor genes may impact reprogramming ability. The pooled iPSCs were also able to differentiate into cerebral organoids. Our procedure enables a multiplex framework of using pooled libraries of donor iPSCs for downstream research and investigation of in vitro phenotypes.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Algoritmos , Linhagem Celular , Genes de Imunoglobulinas
13.
Front Immunol ; 14: 1208610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559724

RESUMO

Introduction: Normal CD30+ B cells represent a distinct B-cell differentiation stage with features of strong activation. We lack an in depth understanding of these cells, because they are not present in peripheral blood and are typically very rare in reactive lymphoid organs. CD30+ B cells have been discussed as a potential precursor population for the malignant CD30+ Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma. As CD30+ B cells can be more numerous in some cases of reactive lymphadenitis, we aimed to characterize these CD30+ B cells in terms of their differentiation stage and clonal composition, also as a means to clarify whether such CD30+ B-cell populations may represent potential precursor lesions of Hodgkin lymphoma. Methods: We microdissected single CD30+ B cells from tissue sections of eight reactive lymph nodes with substantial numbers of such cells and sequenced their rearranged immunoglobulin (Ig) heavy chain V region (IGHV) genes. Results: The CD30+ B cells were polyclonal B cells in all instances, and they not only encompass post-germinal center (GC) B cells with mutated IGHV genes, but also include a substantial fraction of pre-germinal center B cells with unmutated IGHV genes. In five of the lymph nodes, mostly small clonal expansions were detected among the CD30+ B cells. Most of the expanded clones carried somatically mutated IGHV genes and about half of the mutated clones showed intraclonal diversity. Discussion: We conclude that in human reactive lymph nodes with relatively many CD30+ B cells, these cells are a heterogenous population of polyclonal B cells encompassing activated pre-GC B cells as well as GC and post-GC B cells, with some clonal expansions. Because of their polyclonality and frequent pre-GC differentiation stage, there is no indication that such cell-rich CD30+ B-cell populations represent precursor lesions of Hodgkin lymphoma.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/genética , Genes de Imunoglobulinas , Linfonodos/patologia , Cadeias Pesadas de Imunoglobulinas/genética , Diferenciação Celular , Células Clonais
14.
J Mol Diagn ; 25(10): 729-739, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37467928

RESUMO

Next-generation sequencing (NGS)-based clonality analysis allows in-depth assessment of the clonal composition of a sample with high sensitivity for detecting small clones. Within the EuroClonality-NGS Working Group, a protocol for NGS Ig clonality analysis was developed and validated previously. This NGS-based approach was designed to generate small amplicons, making it suitable for samples with suboptimal DNA quality, especially material derived from formalin-fixed, paraffin-embedded tissue. Using expert assessment of NGS Ig clonality results as a reference, a structured algorithmic approach to the assessment of NGS-amplicon-based B-cell clonality analysis was developed. A structured approach with the Detection of clonality through Evaluation of sample quality and assessment of Pattern, Abundance and RaTio (DEPART) algorithm was proposed, which consecutively evaluates sample quality, the pattern of the clonotypes present, the abundance of the most dominant clonotypes, and the ratio between the dominant clonotypes and the background to evaluate the different Ig gene targets. Specific issues with respect to evaluation of the various Ig targets as well as the integration of results of individual targets into a molecular clonality conclusion are discussed and illustrated with case examples. Finally, the importance of interpretation of NGS-based clonality results in clinical and histopathologic contexts is discussed. It is expected that these recommendations will have clinical utility to facilitate proper evaluation of clonality assessment.


Assuntos
Linfócitos B , Genes de Imunoglobulinas , Humanos , DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Algoritmos
15.
Nat Commun ; 14(1): 4419, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479682

RESUMO

Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina , Genes de Imunoglobulinas , Humanos , Genes de Cadeia Pesada de Imunoglobulina/genética , Alelos , Mutação em Linhagem Germinativa , Cadeias Pesadas de Imunoglobulinas/genética
16.
Mol Psychiatry ; 28(10): 4280-4293, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37488168

RESUMO

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.


Assuntos
Transtorno Bipolar , Lítio , Humanos , Lítio/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Transtorno Bipolar/diagnóstico , Genes de Imunoglobulinas , Compostos de Lítio/farmacologia , Compostos de Lítio/uso terapêutico , Linhagem Celular
17.
J Immunol ; 211(3): 486-496, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314411

RESUMO

The human lung carries a unique microbiome adapted to the air-filled, mucous-lined environment, the presence of which requires an immune system capable of recognizing harmful populations while preventing reactions toward commensals. B cells in the lung play a key role in pulmonary immunity, generating Ag-specific Abs, as well as cytokine secretion for immune activation and regulation. In this study, we compared B cell subsets in human lungs versus circulating cells by analyzing patient-paired lung and blood samples. We found a significantly smaller pool of CD19+, CD20+ B cells in the lung relative to the blood. CD27+, IgD-, class-switched memory B cells (Bmems) composed a larger proportion of the pool of pulmonary B cells. The residency marker CD69 was also significantly higher in the lung. We also sequenced the Ig V region genes (IgVRGs) of class-switched Bmems that do, or do not, express CD69. We observed the IgVRGs of pulmonary Bmems to be as heavily mutated from the unmutated common ancestor as those in circulation. Furthermore, we found progenies within a quasi-clone can gain or lose CD69 expression, regardless of whether the parent clone expressed the residency marker. Overall, our results show that despite its vascularized nature, human lungs carry a unique proportion of B cell subsets. The IgVRGs of pulmonary Bmems are as diverse as those in blood, and progenies of Bmems retain the ability to gain or lose residency.


Assuntos
Subpopulações de Linfócitos B , Memória Imunológica , Humanos , Linfócitos B , Genes de Imunoglobulinas , Antígenos CD19/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
19.
Front Immunol ; 14: 1125017, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143651

RESUMO

Introduction: The malignant transformation leading to a maturation arrest in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occurs early in B-cell development, in a pro-B or pre-B cell, when somatic recombination of variable (V), diversity (D), and joining (J) segment immunoglobulin (IG) genes and the B-cell rescue mechanism of VH replacement might be ongoing or fully active, driving clonal evolution. In this study of newly diagnosed BCP-ALL, we sought to understand the mechanistic details of oligoclonal composition of the leukemia at diagnosis, clonal evolution during follow-up, and clonal distribution in different hematopoietic compartments. Methods: Utilizing high-throughput sequencing assays and bespoke bioinformatics we identified BCP-ALL-derived clonally-related IGH sequences by their shared 'DNJ-stem'. Results: We introduce the concept of 'marker DNJ-stem' to cover the entirety of, even lowly abundant, clonally-related family members. In a cohort of 280 adult patients with BCP-ALL, IGH clonal evolution at diagnosis was identified in one-third of patients. The phenomenon was linked to contemporaneous recombinant and editing activity driven by aberrant ongoing DH/VH-DJH recombination and VH replacement, and we share insights and examples for both. Furthermore, in a subset of 167 patients with molecular subtype allocation, high prevalence and high degree of clonal evolution driven by ongoing DH/VH-DJH recombination were associated with the presence of KMT2A gene rearrangements, while VH replacements occurred more frequently in Ph-like and DUX4 BCP-ALL. Analysis of 46 matched diagnostic bone marrow and peripheral blood samples showed a comparable clonal and clonotypic distribution in both hematopoietic compartments, but the clonotypic composition markedly changed in longitudinal follow-up analysis in select cases. Thus, finally, we present cases where the specific dynamics of clonal evolution have implications for both the initial marker identification and the MRD monitoring in follow-up samples. Discussion: Consequently, we suggest to follow the marker DNJ-stem (capturing all family members) rather than specific clonotypes as the MRD target, as well as to follow both VDJH and DJH family members since their respective kinetics are not always parallel. Our study further highlights the intricacy, importance, and present and future challenges of IGH clonal evolution in BCP-ALL.


Assuntos
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Adulto , Humanos , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Genes de Imunoglobulinas , Linfoma de Burkitt/genética , Medula Óssea/patologia
20.
PLoS One ; 18(5): e0285696, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235573

RESUMO

The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH::MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort.


Assuntos
Genes de Imunoglobulinas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estudos de Viabilidade , Reprodutibilidade dos Testes , Translocação Genética , Cadeias Pesadas de Imunoglobulinas/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasia Residual/patologia
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