Cell‐type specificity of anti‐CD45 autoantibodies in systemic lupus erythematosus

Czyzyk, Jan; Fernsten, Philip; Shaw, Melody; Winfield, John B.

doi:10.1002/art.1780390408

Cited by 13 publications

(13 citation statements)

References 55 publications

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“…5B). However, consistent with previous reports, individual sera displayed a significant degree of variability with regard to reactivity toward other isoforms of CD45, in particular an isoform at ϳ180 kDa (10,36). Because in the experiments depicted in Fig.…”

Section: H 4 -34 Abs Bind Specifically To An N-linked Carbohydrate supporting

confidence: 90%

“…By and large, these Abs appear to preferentially bind T cells, but not B cells, suggesting that they recognize a T cell-specific CD45 glycoform (4,7,10,11). Yet, the information summarized above needs to be reconciled with the observation that at least a subset of lupus autoantibodies has the ability to bind B cells possibly by recognizing a B cell-specific CD45 isoform (12)(13)(14).…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

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Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Cappione

Pugh‐Bernard

Anolik

et al. 2004

The Journal of Immunology

103

136

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Anti-lymphocyte autoantibodies are a well-recognized component of the autoimmune repertoire in human systemic lupus erythematosus (SLE) and have been postulated to have pathogenic consequences. Early studies indicated that IgM anti-lymphocyte autoantibodies mainly recognized T cells and identified CD45, a protein tyrosine phosphatase of central significance in the modulation of lymphocyte function, as the main antigenic target on T cells. However, more recent work indicates that lupus autoantibodies can also recognize B cells and that CD45 may also represent their antigenic target. In particular, IgM Abs encoded by VH4.34 appear to have special tropism for B cells, and strong, but indirect evidence suggests that they may recognize a B cell-specific CD45 isoform. Because VH4.34 Abs are greatly expanded in SLE, in the present study we investigated the antigenic reactivity of lupus sera VH4.34 IgG Abs and addressed their contribution to the anti-lymphocyte autoantibody repertoire in this disease. Our biochemical studies conclusively demonstrate that lupus IgG VH4.34 Abs target a developmentally regulated B220-specific glycoform of CD45, and more specifically, an N-linked N-acetyllactosamine determinant preferentially expressed on naive B cells that is sterically masked by sialic acid on B220-positive memory B cells. Strikingly, our data also indicate that this reactivity in SLE sera is restricted to VH4.34 Abs and can be eliminated by depleting these Abs. Overall, our data indicate that VH4.34 Abs represent a major component of the lupus IgG autoantibody repertoire and suggest that the carbohydrate moiety they recognize may act as a selecting Ag in SLE.

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Section: H 4 -34 Abs Bind Specifically To An N-linked Carbohydrate supporting

confidence: 90%

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Cappione

Pugh‐Bernard

Anolik

et al. 2004

The Journal of Immunology

103

136

View full text Add to dashboard Cite

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“…Although the presence of ALAs has been correlated with disease activity (1), lymphocyte subset distortions (2), and various functional abnormalities of T cells, B cells, and monocytes (3)(4)(5), the detailed roles of ALAs remain to be elucidated. One of the main factors that hamper the analysis of ALAs is that ALAs are not classified by their specific target Ags.…”

mentioning

confidence: 99%

Anti-CD69 Autoantibodies Cross-React with Low Density Lipoprotein Receptor-Related Protein 2 in Systemic Autoimmune Diseases

Matsui

Otsuka

et al. 2001

The Journal of Immunology

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We investigated whether autoantibodies to CD69, one of the earliest markers of lymphocyte activation, exist in the sera of patients with systemic autoimmune disease. Serum samples were obtained from patients with rheumatoid arthritis (RA), systemic lupus erythematosus, and Behcet’s disease, and were tested for the presence of anti-CD69 autoantibodies by ELISA and Western blotting using rCD69 fusion proteins. IgG-type autoantibodies to CD69 were detected in the sera of 38.3% of the RA patients, 14.5% of the systemic lupus erythematosus patients, and 4.0% of the patients with Behcet’s disease. Among those with RA, the anti-CD69 autoantibody-positive patients had a higher serum level of rheumatoid factors and a more accelerated erythrocyte sedimentation rate than the anti-CD69 autoantibody-negative patients. Further, the predominant epitope on the CD69 molecule to which most of the anti-CD69 autoantibody-positive serum samples exclusively reacted, was mapped at the C terminus of CD69. Of interest, this epitope is homologous to a stretch of amino acids in the protein sequence of low-density lipoprotein receptor-related protein 2 (LRP2), which is a receptor for multiple ligands including β-very low density lipoprotein and is also an autoantigen responsible for Heymann nephritis in rats. The anti-CD69 autoantibody cross-reacted to LRP2 through the homologous amino acid sequence. To our knowledge, this is the first evidence of the existence of anti-CD69 autoantibodies. This autoantibody may modulate the function of CD69- and LRP2-expressing cells.

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“…Activated T cells, which exhibit a higher density of many surface membrane antigens than do resting cells and also express neoantigens, were found to be special targets of such autoantibodies [8]. Considerable information also has accrued concerning IgM ALAB target antigens: IL-2 receptor [9]; b 2 -microglobulin [10,11]; HLA class I heavy chains [12]; a DR framework epitope [13]; IgD, which functions as an antigen receptor on B cells [14]; B and T cell membrane glycosphingolipids [15]; CD45 [16][17][18]; and synthetic T cell receptor (TCR) peptides [19]. Almost certainly, there are additional specificities that have not yet been characterized.…”

mentioning

confidence: 99%

Are anti-ribosomal P protein antibodies a type of anti-lymphocyte antibody?

Winfield

1997

Clinical and Experimental Immunology

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Stafford and colleagues report in this issue that IgG anti-ribosomal P protein antibodies (anti-P) in systemic lupus erythematosus (SLE) bind to a human lymphocyte surface membrane-associated 38-kD molecule apparently identical to the P 0 ribosomal protein [1]. Their data extend those of Koren et al. [2], who demonstrated cell surface reactivity of anti-P with human hepatoma, neuroblastoma, and skin fibroblast cell lines. Although these are not novel observations-sporadic descriptions of cell surface binding by autoantibodies to various nuclear and intracytoplasmic antigens have been in the literature for 20 years (reviewed in [3])-special care was taken by Stafford to minimize the ambiguity inherent in experiments of this type. IgG Fc/Fc receptor interactions were ruled out. Specificity of binding was established by antigen inhibition, use of affinity-purified anti-P, and immunoblotting. Reactivity of anti-P with viable cells and ribosome-free plasma membrane preparations was demonstrated. And experiments with cell surface proteins purified by biotinylation revealed reactivity only with a 38-kD molecule, not the small P 1 and P 2 ribosomal proteins that would be expected if ribosomes released from dead cells were becoming attached to living cells. While it would have been nice to also have immunoprecipitation and complementdependent cytotoxicity data, and begging the question of how a ribosomal protein gets to the outer surface of the cell in the first place, Stafford's observations clearly support her conclusions that 'anti-ribosomal antibodies are a subset of anti-lymphocyte autoantibodies'.If anti-P antibodies are a subset of anti-lymphocyte antibodies (ALAB), they certainly differ from the traditional version, which are described below and in Table 1.Originally described as 'cold-lymphocytotoxins' because they kill lymphocytes in the presence of complement better at 15ЊC than at 37ЊC [4], classic IgM ALAB in SLE react broadly with autologous lymphocytes and with lymphocytes from unrelated donors (reviewed in [5]). Early studies established a relative specificity for T cells, especially thymocytes, and detected interesting specificities for functionally significant T cell subsets. IgM antibodies to B cells were described, as well, and are at least partially distinct from autoantibodies to T cells [6]. More recent data have substantially clarified the nature and potential significance of autoantibodies in this system. Thus, reactivity of T cells to IgM ALAB was shown to be dependent primarily on the presence of antigen(s) that are shared by CD4 + and CD8 + subsets, with a superimposed specificity for an additional antigen(s) expressed on CD4 + T cells [7]. Activated T cells, which exhibit a higher density of many surface membrane antigens than do resting cells and also express neoantigens, were found to be special targets of such autoantibodies [8] Most patients with SLE express IgM ALAB, which vary in titre with disease activity status in the same fashion as anti-dsDNA autoantibodies [6,20]. This association...

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Cell‐type specificity of anti‐CD45 autoantibodies in systemic lupus erythematosus

Cited by 13 publications

References 55 publications

Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Anti-CD69 Autoantibodies Cross-React with Low Density Lipoprotein Receptor-Related Protein 2 in Systemic Autoimmune Diseases

Are anti-ribosomal P protein antibodies a type of anti-lymphocyte antibody?

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