HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes.

Dörken, B; Moldenhauer, G; Pezzutto, Antonio; Schwartz, Robert J.; Feller, A. C.; Kiesel, Sophie; Nadler, LM

doi:10.4049/jimmunol.136.12.4470

Cited by 153 publications

(4 citation statements)

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“…Rituximab treatment led to significant reductions in serum total IgG (median [range] baseline 12.0 gm/liter [5.50–20.7] versus nadir 10.5 [5.40–15.1]) ( P = 0.001), total IgM (baseline 1.30 gm/liter [0.60–3.60] versus nadir 1.0 [0.30–2.10]) ( P < 0.001), and total IgA (baseline 1.95 gm/liter [1.0–6.35] versus nadir 1.60 [1.0–5.70]) ( P = 0.001). Also, ACPA IgG titers decreased significantly from 443 AU/ml (range 56–1,280) at baseline to a nadir of 364 AU/ml (44–897) ( P = 0.012), IgM‐RF titers decreased from 49 IU/ml (14–205) at baseline to a nadir of 25 (1–184) ( P < 0.001), and ACPA IgM titers decreased from 61 AU/ml (34–251) at baseline to a nadir of 34 (20–71) ( P = 0.009) (Figure 2A). Of note, in the majority of patients a gradual decrease was observed, generally reaching lowest levels 24 weeks after rituximab treatment.…”

Section: Resultsmentioning

confidence: 95%

“…CD20 is expressed earlier in the development of B cells than is CD22. Circulating IgM+,IgD+ naive B cells express both CD20 and CD22 (24–28), and CD22 expression is closely linked to surface Ig expression, notably surface IgD, on B cells. Importantly, germinal center B cells, plasma cells, and in vitro–activated B cells cease to express CD22 (29, 30).…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Teng

Levarht

Hashemi

et al. 2007

Arthritis & Rheumatism

167

113

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Objective. Anti-CD20-mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy.Methods. Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. CD19؉ and CD20؉ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a؉ and cytoplasmic CD20؉ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme-linked immunosorbent assay.Results. Rituximab effectively depleted the CD20؉ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti-citrullinated pro- Conclusion. These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Teng

Levarht

Hashemi

et al. 2007

Arthritis & Rheumatism

167

113

View full text Add to dashboard Cite

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“…B cell subgroups (eg naive, switched etc.) were manually determined using differentially expressed B cell markers 38 , 39 . To confirm the identity of each cell, Reference-Based Single-Cell RNA-Seq Annotation (SingleR v. 3.13) was employed (Fig.…”

Section: Methodsmentioning

confidence: 99%

Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

et al. 2023

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Dysfunction of interleukin-10 producing regulatory B cells has been associated with the pathogenesis of autoimmune diseases, but whether regulatory B cells can be therapeutically induced in humans is currently unknown. Here we demonstrate that a subset of activated B cells expresses CD25, and the addition of low-dose recombinant IL-2 to in vitro stimulated peripheral blood and splenic human B cells augments IL-10 secretion. Administration of low dose IL-2, aldesleukin, to patients increases IL-10-producing B cells. Single-cell RNA sequencing of circulating immune cells isolated from low dose IL2-treated patients reveals an increase in plasmablast and plasma cell populations that are enriched for a regulatory B cell gene signature. The transcriptional repressor BACH2 is significantly down-regulated in plasma cells from IL-2-treated patients, BACH2 binds to the IL-10 gene promoter, and Bach2 depletion or genetic deficiency increases B cell IL-10, implicating BACH2 suppression as an important mechanism by which IL-2 may promote an immunoregulatory phenotype in B cells.

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“…InO was designed to deliver the chemotherapeutic payload calicheamicin to cells expressing CD22, a type I transmembrane protein solely expressed on B-lineage cells. 1,2 Calicheamicin is a highly potent toxin that binds to the DNA minor grove and induces double-stranded DNA breaks (DSBs). 3 InO elicits high rates of remission and undetectable measurable residual disease (MRD), and represents an advance in therapeutic options for relapsed/refractory (R/R) B-cell ALL.…”

Section: Introductionmentioning

confidence: 99%

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL

Zhao,

Short,

Kantarjian

et al. 2023

Preprint

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Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response to InO. AcquiredCD22mutations were observed in 11% (3/27) of post-InO relapsed tumor samples. There were multipleCD22mutations per sample and the mechanisms of CD22 escape included protein truncation, protein destabilization, and epitope alteration. Hypermutation by error-prone DNA damage repair (alternative end-joining, mismatch repair deficiency) drove CD22 escape. Acquired loss-of-function mutations inTP53,ATMandCDKN2Awere observed, suggesting compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. The escape strategies within and beyond antigen loss to CD22-targeted therapy elucidated in this study provide insights into improving therapeutic approaches and overcoming resistance.KEY POINTSWe identified multiple mechanisms of CD22 antigen escape from inotuzumab ozogamicin, including protein truncation, protein destabilization, and epitope alteration.Hypermutation caused by error-prone DNA damage repair was a driver of CD22 mutation and escape.VISUAL ABSTRACT

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HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes.

Cited by 153 publications

References 0 publications

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL

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