The soluble form of CD83 is present at elevated levels in a number of hematological malignancies

Hock, Barry D.; Haring, Lisa F.; Steinkasserer, Alexander; Taylor, K.; Patton, W. N.; McKenzie, Judith L.

doi:10.1016/s0145-2126(03)00255-8

Cited by 66 publications

(66 citation statements)

References 14 publications

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“…16 Moreover, genes involved in B-cell development, such as BTK, CD69, CD83, IRF8 and ITPR1, were deregulated in WM-BL: the overexpression of CD69 and CD83 in WM could be useful for diagnostic applications based on immunophenotypic analysis. 17 Of special interest as a potential therapeutic target is the upregulation in WM-BL of CEACAM1 gene, which exhibits potent angiogenic properties and is a major effector of vascular endothelial growth factor (VEGF). 18 When comparing the expression profile of WM-PC with that of NPC, a total of 498 genes were differentially expressed, all of them upregulated in the WM-PC group.…”

Section: Resultsmentioning

confidence: 99%

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

et al. 2007

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The tumoral clone of Waldenströ m's macroglobulinemia (WM) shows a wide morphological heterogeneity, which ranges from B lymphocytes (BL) to plasma cells (PC). By means of genomewide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell counterparts from chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes downregulated in WM-BL were IL4R, which plays a relevant role in CLL B-cell survival, and BACH2, which participates in the development of class-switched PC. Interestingly, one of the upregulated genes in WM-BL was IL6. A set of four genes was able to discriminate clonal BL from WM and CLL: LEF1 (WNT/b-catenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5, which was overexpressed in WM-PC, and IRF4 and BLIMP1, which were underexpressed. In addition, three of the target genes activated by PAX5 -CD79, BLNK and SYK -were upregulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell counterpart.

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Section: Resultsmentioning

confidence: 99%

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

et al. 2007

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“…Soluble CD83 has been identified in the sera of healthy individuals, supporting a role of this protein variant under steady-state conditions. Interestingly, the amount of soluble CD83 was elevated in the sera of several leukemia patients (21), which might lead to an increased threshold for T cell activation in these patients. After induction of inflammatory cytokines by polyclonal activators such as PHA, these inhibitory CD83-splice products are down-regulated, which might relieve this inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

Alternative Splicing Generates Putative Soluble CD83 Proteins That Inhibit T Cell Proliferation

Dudziak¹,

Nimmerjahn²,

Bornkamm³

et al. 2005

The Journal of Immunology

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CD83 is expressed on mature dendritic cells and activated lymphocytes and has been implicated to play an important role during T cell development in the thymus. In contrast, not much is known about the function of CD83 in the periphery. Soluble forms of CD83 have been detected in the serum, but neither the function nor the mechanism of how these soluble forms of CD83 are generated are fully understood. In this study, we report the identification of four different transcripts of CD83 in unstimulated PBMCs. Sequence analysis demonstrated that the longest form codes for transmembrane CD83 (CD83-TM), whereas the smaller transcripts are splice variants of full-length CD83, coding for putative soluble CD83 proteins. Stimulation of PBMCs with PHA, TNF-α, or LPS leads to the up-regulation of the full-length CD83 transcript and to a strong down-regulation of two of the three smaller transcripts. The smallest CD83 splice product can be translated efficiently into protein, and recombinant soluble CD83 shows a strong inhibitory effect on T cell proliferation in MLRs. Our results suggest that the constitutive production of soluble forms of CD83 under steady-state conditions may have an important function in regulating immune homeostasis.

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“…Serum CD83 is also detectable in some neonates [40]. Increased levels of soluble CD83 are found in synovial fluid from rheumatoid arthritis patients [41], and soluble CD83 was detected at levels >1 ng/ml levels in sera from some chronic lymphocytic leukemia or mantle cell lymphoma patients [42]. Serum ultracentrifugation does not diminish CD83 levels, arguing that serum CD83 does not reflect the presence of circulating exosomes or cell debris.…”

Section: Serum Cd83mentioning

confidence: 99%

Dendritic cell CD83: A therapeutic target or innocent bystander?

Prazma

Tedder

2008

Immunology Letters

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CD83 represents an intriguing target for immunotherapy due to its preferential expression on mature DCs, the most efficient of antigen presenting cells. Based on its restricted expression pattern, structure, and the paucity of CD4 + T cells in CD83-deficient mice, multiple immunologically important functions for CD83 during immune responses have been proposed. Indeed, several studies have reported that CD83 blockade using soluble receptor constructs inhibits T cell responses in vitro and in vivo, can affect autoimmune disease development and progression, and can inhibit transplant rejection. However, others have not been able to reproduce some of these findings, and antigen presenting cells deficient in CD83 expression or expressing a mutated form of CD83 induce normal T cell responses in vitro. This review examines the controversy surrounding CD83 function, alleged CD83 ligands, the potential therapeutic utility of recombinant proteins targeting CD83 function, and the importance of soluble serum CD83. While the validity of multiple previous studies needs to be confirmed, CD83 remains a fascinating cell surface molecule with a unique pattern of expression that has multiple confirmed functions in regulating immune system development and function.

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The soluble form of CD83 is present at elevated levels in a number of hematological malignancies

Cited by 66 publications

References 14 publications

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals

Alternative Splicing Generates Putative Soluble CD83 Proteins That Inhibit T Cell Proliferation

Dendritic cell CD83: A therapeutic target or innocent bystander?

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