scholarly journals Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome

2020 ◽  
Vol 11 ◽  
Author(s):  
Shelly Pathak ◽  
Dorota Rowczenio ◽  
Samuel Lara-Reyna ◽  
Mark Kacar ◽  
Roger Owen ◽  
...  
Keyword(s):  
B Cell ◽  
Late Onset ◽  
Protein Microarray ◽  
Vdj Recombination ◽  
Onset Condition ◽  
Regional Dynamics ◽  
Schnitzler Syndrome ◽  
Gene Usage ◽  
Insight Into ◽  
Cell Clonality

The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder.

scholarly journals T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 340
Author(s):  
Ming Liang Oon ◽  
Jing Quan Lim ◽  
Bernett Lee ◽  
Sai Mun Leong ◽  
Gwyneth Shook-Ting Soon ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Copy Number ◽  
Nk Cell ◽  
Cell Receptor ◽  
T Cell Lymphomas ◽  
Number Variation ◽  
Diagnostic Applications ◽  
Cell Clonality

T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.

Schnitzler syndrome associated with systemic marginal zone B-cell lymphoma

2006 ◽  
Vol 155 (4) ◽  
pp. 827-829 ◽  
Author(s):  
S. Dalle ◽  
B. Balme ◽  
C. Sebban ◽  
C. Pariset ◽  
F. Berger ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Schnitzler Syndrome

scholarly journals Monoclonal antibodies reactive with hairy cell leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 320-325 ◽  
Author(s):  
L Visser ◽  
A Shaw ◽  
J Slupsky ◽  
H Vos ◽  
S Poppema
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Small Population ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hairy Cells ◽  
A Minor ◽  
Insight Into

Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibody B-ly 2 can be considered a pan-B cell reagent and generally reacts similar to CD22 antibodies. Antibody B-ly 6 is reactive with the same antigen as CD11c (p150/95), an antigen that is present on hairy cell leukemia, macrophages, and a minor subpopulation of lymphocytes. Antibody B-ly 7 is a unique antibody reactive with 144 Kd antigen present only on hairy cell leukemia and a very small population of normal B lymphocytes. This subpopulation may be the counterpart of hairy cells.

Non-invasive B-cell clonality markers may help in the rational approach to HCV SVR cryoglobulinemic patients with persisting manifestations

2018 ◽  
Vol 50 (3) ◽  
pp. e356
Author(s):  
S. Lorini ◽  
L. Gragnani ◽  
V. Santarlasci ◽  
M. Monti ◽  
U. Basile ◽  
...  
Keyword(s):  
B Cell ◽  
Rational Approach ◽  
Non Invasive ◽  
Cell Clonality

scholarly journals Insight into origins, mechanisms, and utility of DNA methylation in B-cell malignancies

Blood ◽  
2018 ◽  
Vol 132 (10) ◽  
pp. 999-1006 ◽  
Author(s):  
Christopher C. Oakes ◽  
Jose I. Martin-Subero
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Driver Mutations ◽  
Detailed Knowledge ◽  
B Cell Differentiation ◽  
B Cell Malignancies ◽  
Essential Information ◽  
A Genome ◽  
Cytidine Deaminase Activity ◽  
Insight Into

AbstractUnderstanding how tumor cells fundamentally alter their identity is critical to identify specific vulnerabilities for use in precision medicine. In B-cell malignancy, knowledge of genetic changes has resulted in great gains in our understanding of the biology of tumor cells, impacting diagnosis, prognosis, and treatment. Despite this knowledge, much remains to be explained as genetic events do not completely explain clinical behavior and outcomes. Many patients lack recurrent driver mutations, and said drivers can persist in nonmalignant cells of healthy individuals remaining cancer-free for decades. Epigenetics has emerged as a valuable avenue to further explain tumor phenotypes. The epigenetic landscape is the software that powers and stabilizes cellular identity by abridging a broad genome into the essential information required per cell. A genome-level view of B-cell malignancies reveals complex but recurrent epigenetic patterns that define tumor types and subtypes, permitting high-resolution classification and novel insight into tumor-specific mechanisms. Epigenetic alterations are guided by distinct cellular processes, such as polycomb-based silencing, transcription, signaling pathways, and transcription factor activity, and involve B-cell-specific aspects, such as activation-induced cytidine deaminase activity and germinal center–specific events. Armed with a detailed knowledge of the epigenetic events that occur across the spectrum of B-cell differentiation, B-cell tumor–specific aberrations can be detected with improved accuracy and serve as a model for identification of tumor-specific events in cancer. Insight gained through recent efforts may prove valuable in guiding the use of both epigenetic- and nonepigenetic-based therapies.

The Relevance of VDJ PCR Protocols in Detecting B-Cell Clonal Expansion in Lymphomas and Other Lymphoproliferative Disorders

1995 ◽  
Vol 81 (6) ◽  
pp. 405-409 ◽  
Author(s):  
Valli De Re ◽  
Salvatore De Vita ◽  
Antonino Carbone ◽  
Gianfranco Ferraccioli ◽  
Annunziata Gloghini ◽  
...  
Keyword(s):  
B Cell ◽  
Wide Spectrum ◽  
Clonal Expansion ◽  
Lymphoproliferative Disorders ◽  
Region Gene ◽  
B Cell Malignancy ◽  
Polymerase Chain ◽  
Hodgkin's Lymphomas ◽  
Cell Clonality ◽  
Cell Clonal Expansion

Aims and background The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB). Methods 83 SB-rearranged B-cell non-Hodgkin's lymphomas (NHL) of different histotype, 22 cases of SB-unrearranged classical Hodgkin's disease (HD), 18 cases of HIV-related reactive lymphadenopathy, and 4 frankly pre-lymphomatous lesions (MESA) in the course of Sjögren's syndrome were investigated by 2 different VDJ PCR protocols (FR3, FR2). Results The detection rate in NHL was 64% and 71% using the protocols FR3 and FR2, respectively. However, the overall VDJ PCR efficacy increased to 81% by combining the results of both protocols. In addition, differences in the combined, as well as in the single FR3 or FR2 protocol efficacy, were noted in the different NHL subgroups. B-cell clonality was also detected in 4/22 (18%) SB-unrearranged classical HD cases and in 2/18 (11%) reactive lymphadenopathy cases, whereas it was demonstrated in all the MESA lesions, 2 of them being SB-negative. Conclusions VDJ PCR represents a useful and rapid technique to detect B-cell clonality in NHL, although with some differences depending on the NHL histotype and the panel of primers employed. The technique may also be of value to investigate the possible progression of early B-cell clonal expansion into frankly B-cell malignancy and to contribute to the controversy about the clonal lineage origin of the putative HD malignant cells.

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