Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss

Donna A. Culton; Matilda W. Nicholas; Donna O. Bunch; Quan Li Zhen; Thomas B. Kepler; Mary Anne Dooley; Chandra Mohan; Patrick Nachman; Stephen H. Clarke

doi:10.1007/s10875-006-9051-1

Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss

Donna A. Culton, Matilda W. Nicholas, Donna O. Bunch, Quan Li Zhen, Thomas B. Kepler, Mary Anne Dooley, Chandra Mohan, Patrick Nachman, Stephen H. Clarke

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The naïve B cells of nearly all SLE and ANCA-SVV patients express ∼20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19^hi memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19^hi SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.

Original language	English (US)
Pages (from-to)	53-68
Number of pages	16
Journal	Journal of Clinical Immunology
Volume	27
Issue number	1
DOIs	https://doi.org/10.1007/s10875-006-9051-1
State	Published - Jan 2007
Externally published	Yes

Bibliographical note

Funding Information:
We gratefully acknowledge the Flow Cytometry Facility at the University of North Carolina. We also extend our thanks to Sarah Thielman, Brenda Meier, Marcus R. Johnson, and Pamela Sullivan for their help in acquiring patient samples. This work was supported by National Institutes of Health Grants AI29576, AI43587 and DK58335. D. A. C. was supported by a Training Grant in Dermatological Research, T32 AR07369.

Keywords

ANCA small-vessel vasculitis
Autoantibodies
Autoimmunity
B lymphocytes
CD19
Systemic lupus erythematosus

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title = "Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss",

abstract = "We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The na{\"i}ve B cells of nearly all SLE and ANCA-SVV patients express ∼20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19hi memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19hi SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.",

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author = "Culton, {Donna A.} and Nicholas, {Matilda W.} and Bunch, {Donna O.} and Zhen, {Quan Li} and Kepler, {Thomas B.} and Dooley, {Mary Anne} and Chandra Mohan and Patrick Nachman and Clarke, {Stephen H.}",

note = "Funding Information: We gratefully acknowledge the Flow Cytometry Facility at the University of North Carolina. We also extend our thanks to Sarah Thielman, Brenda Meier, Marcus R. Johnson, and Pamela Sullivan for their help in acquiring patient samples. This work was supported by National Institutes of Health Grants AI29576, AI43587 and DK58335. D. A. C. was supported by a Training Grant in Dermatological Research, T32 AR07369.",

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AU - Mohan, Chandra

AU - Nachman, Patrick

AU - Clarke, Stephen H.

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N2 - We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The naïve B cells of nearly all SLE and ANCA-SVV patients express ∼20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19hi memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19hi SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.

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Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss

Abstract

Bibliographical note

Keywords

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