Serum Antibodies and Monoclonal Antibodies Secreted by Thymic B-Cell Clones from Patients with Myasthenia Gravis Define Striational Antigens

1987 ◽  
Vol 505 (1 Myasthenia Gr) ◽  
pp. 168-179 ◽  
Author(s):  
CAROL L. WILLIAMS ◽  
VANDA A. LENNON ◽  
MARIKO Y. MOMOI ◽  
FRANK M. HOWARD
Keyword(s):  
Monoclonal Antibodies ◽  
Myasthenia Gravis ◽  
B Cell ◽  
Serum Antibodies ◽  
Cell Clones

Myasthenia Gravis

2019 ◽  
pp. 651-657
Author(s):  
Maximiliano A. Hawkes ◽  
Eelco F. M. Wijdicks
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
B Cell ◽  
Age At Onset ◽  
Serum Antibodies ◽  
End Plate ◽  
Thymic Tumor ◽  
Work Up

Myasthenia gravis (MG) is a well-characterized B-cell–mediated disease caused by autoantibodies against targets located in the postsynaptic end plate of the neuromuscular junction. Fluctuating weakness and fatigability are clinical hallmarks of this disease. MG can be divided into subgroups based on the age at onset, serum antibodies, and thymic tumor, and different clinical courses can be anticipated with each. This chapter describes general concepts about MG, focusing on the triage, work-up, and management of severe myasthenic exacerbation (crisis).

scholarly journals Elevated N-glycosylation of immunoglobulin G variable regions in myasthenia gravis highlights a commonality across autoantibody-associated diseases

2021 ◽  
Author(s):  
Caleigh Mandel-Brehm ◽  
Miriam L. Fichtner ◽  
Ruoyi Jiang ◽  
Valerie J. Winton ◽  
Sara E. Vazquez ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Myasthenia Gravis ◽  
B Cell ◽  
Immunoglobulin G ◽  
Somatic Hypermutation ◽  
Gene Segment ◽  
Cell Repertoire ◽  
Variable Regions ◽  
Receptor Repertoire ◽  
Glycosylation Sites

AbstractElevated N-linked glycosylation of immunoglobulin G variable regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design included adaptive immune receptor repertoire sequencing to quantify and characterize N-glycosylation sites in the global B cell receptor repertoire, proteomics to examine glycosylation patterns of the circulating IgG, and production of human-derived recombinant autoantibodies, which were studied with mass spectrometry and antigen binding assays to confirm occupation of glycosylation sites and determine whether they alter binding. We found that the frequency of IgG-VN-Glyc motifs was increased in the B cell repertoire of MG patients when compared to healthy donors. Motifs were introduced by both biased V gene segment usage and somatic hypermutation. IgG-VN-Glyc could be observed in the circulating IgG in a subset of MG patients. Autoantigen binding, by patient-derived MG autoantigen-specific monoclonal antibodies with experimentally confirmed presence of IgG-VN-Glyc, was not altered by the glycosylation. Our findings extend prior work on patterns of variable region N-linked glycosylation in autoimmunity to MG subtypes. Although occupied IgG-VN-Glyc motifs are found on MG autoantigen-specific monoclonal antibodies, they are not required for binding to the autoantigen in this disease.

scholarly journals Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis

2020 ◽  
Vol 117 (48) ◽  
pp. 30649-30660 ◽  
Author(s):  
Ruoyi Jiang ◽  
Kenneth B. Hoehn ◽  
Casey S. Lee ◽  
Minh C. Pham ◽  
Robert J. Homer ◽  
...  
Keyword(s):  
B Cells ◽  
Myasthenia Gravis ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Cell Clones ◽  
Autoantibody Titer ◽  
Repertoire Sequencing ◽  
Symptom Measures

Myasthenia gravis (MG) is a neuromuscular, autoimmune disease caused by autoantibodies that target postsynaptic proteins, primarily the acetylcholine receptor (AChR) and inhibit signaling at the neuromuscular junction. The majority of patients under 50 y with AChR autoantibody MG have thymic lymphofollicular hyperplasia. The MG thymus is a reservoir of plasma cells that secrete disease-causing AChR autoantibodies and although thymectomy improves clinical scores, many patients fail to achieve complete stable remission without additional immunosuppressive treatments. We speculate that thymus-associated B cells and plasma cells persist in the circulation after thymectomy and that their persistence could explain incomplete responses to resection. We studied patients enrolled in a randomized clinical trial and used complementary modalities of B cell repertoire sequencing to characterize the thymus B cell repertoire and identify B cell clones that resided in the thymus and circulation before and 12 mo after thymectomy. Thymus-associated B cell clones were detected in the circulation by both mRNA-based and genomic DNA-based sequencing. These antigen-experienced B cells persisted in the circulation after thymectomy. Many circulating thymus-associated B cell clones were inferred to have originated and initially matured in the thymus before emigration from the thymus to the circulation. The persistence of thymus-associated B cells correlated with less favorable changes in clinical symptom measures, steroid dose required to manage symptoms, and marginal changes in AChR autoantibody titer. This investigation indicates that the diminished clinical response to thymectomy is related to persistent circulating thymus-associated B cell clones.

scholarly journals Antibody-based therapy of leukaemia

2009 ◽  
Vol 11 ◽  
Author(s):  
John C. Morris ◽  
Thomas A. Waldmann
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Gemtuzumab Ozogamicin ◽  
Cell Leukaemia ◽  
Target Cells ◽  
Immune Effector ◽  
Effector Cells ◽  
Prolymphocytic Leukaemia ◽  
Immune Effector Cells

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies – the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab – are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.

Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stromain vitro prevent B cell differentiationin vivo

1991 ◽  
Vol 21 (9) ◽  
pp. 2043-2049 ◽  
Author(s):  
Beat A. Imhof ◽  
Claude Schlienger ◽  
Klaus Handloser ◽  
Barbara Hesse ◽  
Michaela Slanicka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
B Cell

Myasthenia gravis induced by monoclonal antibodies to acetylcholine receptors

Nature ◽  
1980 ◽  
Vol 285 (5762) ◽  
pp. 238-240 ◽  
Author(s):  
Vanda A. Lennon ◽  
Edward H. Lambert
Keyword(s):  
Monoclonal Antibodies ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors
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