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Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.

Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N - Arthritis Res. (2000)

Bottom Line: These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells.Furthermore, some of these individual expansions can persist over extended periods of time.A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.

ABSTRACT
The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

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Related in: MedlinePlus

Analyses of paired samples of blood (B) and synovial fluid (SF) B				cells from the same rheumatoid arthritis patient. Results using both the				genomic DNA-based assay and the complementary (c)DNA-based assay for the three				major immunoglobulin isotypes (M, G, and A) are shown. Note that certain				clones, as represented by individual HCDR3 lengths, are restricted to the blood				(▸), others to the joint (▹), and others are common to both compartments				(♦). E, expanded clone; A, activated clone; E+A, same clone that is both				expanded and activated.
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Figure 2: Analyses of paired samples of blood (B) and synovial fluid (SF) B cells from the same rheumatoid arthritis patient. Results using both the genomic DNA-based assay and the complementary (c)DNA-based assay for the three major immunoglobulin isotypes (M, G, and A) are shown. Note that certain clones, as represented by individual HCDR3 lengths, are restricted to the blood (▸), others to the joint (▹), and others are common to both compartments (♦). E, expanded clone; A, activated clone; E+A, same clone that is both expanded and activated.

Mentions: We analyzed the peripheral blood, synovial fluid, and synovial tissue B cells of rheumatoid arthritis patients (n = 20, 10, and 5, respectively) using the genomic DNA- and cDNA-based fingerprinting assays to develop an understanding of the diversity of the B cells in these compartments. Figures 2 and 3 are illustrations of representative patients for whom concomitant blood and synovial fluid or blood and synovial tissue samples were available. In order to simplify the Figures, only the results for two large VH families (VH1 and VH3) and two small VH families (VH5 and VH6) are provided, although assays for each VH family and each major CH family (μ,γ, and α) were performed and revealed similar findings.


Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.

Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N - Arthritis Res. (2000)

Analyses of paired samples of blood (B) and synovial fluid (SF) B				cells from the same rheumatoid arthritis patient. Results using both the				genomic DNA-based assay and the complementary (c)DNA-based assay for the three				major immunoglobulin isotypes (M, G, and A) are shown. Note that certain				clones, as represented by individual HCDR3 lengths, are restricted to the blood				(▸), others to the joint (▹), and others are common to both compartments				(♦). E, expanded clone; A, activated clone; E+A, same clone that is both				expanded and activated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC17803&req=5

Figure 2: Analyses of paired samples of blood (B) and synovial fluid (SF) B cells from the same rheumatoid arthritis patient. Results using both the genomic DNA-based assay and the complementary (c)DNA-based assay for the three major immunoglobulin isotypes (M, G, and A) are shown. Note that certain clones, as represented by individual HCDR3 lengths, are restricted to the blood (▸), others to the joint (▹), and others are common to both compartments (♦). E, expanded clone; A, activated clone; E+A, same clone that is both expanded and activated.
Mentions: We analyzed the peripheral blood, synovial fluid, and synovial tissue B cells of rheumatoid arthritis patients (n = 20, 10, and 5, respectively) using the genomic DNA- and cDNA-based fingerprinting assays to develop an understanding of the diversity of the B cells in these compartments. Figures 2 and 3 are illustrations of representative patients for whom concomitant blood and synovial fluid or blood and synovial tissue samples were available. In order to simplify the Figures, only the results for two large VH families (VH1 and VH3) and two small VH families (VH5 and VH6) are provided, although assays for each VH family and each major CH family (μ,γ, and α) were performed and revealed similar findings.

Bottom Line: These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells.Furthermore, some of these individual expansions can persist over extended periods of time.A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.

ABSTRACT
The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

Show MeSH
Related in: MedlinePlus