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Enhancement of Membrane B7-H3 Costimulatory Molecule but Reduction of Its Soluble Form in Multiple Sclerosis

  • Original Research
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Abstract

Purpose

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system mediated by T cells. B7-H3 plays a diverse role in regulating T cell responses. However, its expression and clinical significance in MS are not well known. This study analyzed the expression of membrane B7-H3 (mB7-H3) and levels of soluble B7-H3 (sB7-H3) in MS patients to determine its clinical significance.

Methods

Peripheral blood (PB) or cerebrospinal fluid (CSF) samples from healthy controls, other noninflammatory neurological disorders, viral encephalitis, and MS patients were collected. Expression of mB7-H3 on immune cells was detected by flow cytometry. Levels of sB7-H3 in serum or CSF samples were measured by ELISA.

Results

mB7-H3 expression was up-regulated in CSF from MS patients compared to PB (p < 0.001). However, serum or CSF levels of sB7-H3 in MS patients were significantly lower than those in controls (p < 0.05). Relapsing-MS patients had higher CSF mB7-H3 expression than the remitting subgroup. Relapsing-MS patients had decreased serum and CSF sB7-H3 levels compared with the remitting subgroup. Neurological deficits showed negative correlations with serum or CSF sB7-H3 levels, but a positive correlation with CSF mB7-H3 expression. Methylprednisolone therapy significantly elevated sB7-H3 levels and reduced mB7-H3 expression compared with pre-therapy levels. sB7-H3 levels did not correlate with mB7-H3 expression.

Conclusions

We demonstrated enhanced mB7-H3 expression and reduced sB7-H3 levels in MS patients which correlated with the clinical characteristics of MS patients. These results suggest that B7-H3 may be a promising biomarker and associated with the pathogenesis of MS.

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Abbreviations

MS:

Multiple sclerosis

CNS:

Central nervous system

B7-H3R:

B7-H3 receptor

mB7-H3:

membrane B7-H3

sB7-H3:

soluble B7-H3

PB:

Peripheral blood

CSF:

Cerebrospinal fluid

HC:

Healthy controls

OND:

Other noninflammatory neurological disorders

VE:

Viral encephalitis

EDSS:

Expanded Disability Status Scale

ELISA:

Enzyme-linked immunosorbent assay

MFI:

Mean fluorescence intensity

References

  1. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502–17.

    Article  PubMed  CAS  Google Scholar 

  2. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8:913–9.

    Article  PubMed  CAS  Google Scholar 

  3. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–48.

    Article  PubMed  Google Scholar 

  4. Bour-Jordan H, Blueston JA. CD28 function: a balance of costimulatory and regulatory signals. J Clin Immunol. 2002;22:1–7.

    Article  PubMed  CAS  Google Scholar 

  5. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9.

    Article  PubMed  CAS  Google Scholar 

  6. Yoshinaga SK, Whoriskey JS, Khare SD, Sarmiento U, Guo J, Horan T, et al. T-cell co-stimulation through B7RP-1 and ICOS. Nature. 1999;402:827–32.

    Article  PubMed  CAS  Google Scholar 

  7. Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18:849–61.

    Article  PubMed  CAS  Google Scholar 

  8. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, et al. B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2001;2:269–74.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang G, Hou J, Shi J, Yu G, Lu B, Zhang X. Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum. Immunology. 2008;123:538–46.

    Article  PubMed  CAS  Google Scholar 

  10. Suh WK, Gajewska BU, Okada H, Gronski MA, Bertram EM, Dawicki W, et al. The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol. 2003;4:899–906.

    Article  PubMed  CAS  Google Scholar 

  11. Prasad DV, Nguyen T, Li Z, Yang Y, Duong J, Wang Y, et al. Murine B7-H3 is a negative regulator of T cells. J Immunol. 2004;173:2500–6.

    PubMed  CAS  Google Scholar 

  12. Castriconi R, Dondero A, Augugliaro R, Cantoni C, Carnemolla B, Sementa AR, et al. Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci. 2004;101:12640–5.

    Article  PubMed  CAS  Google Scholar 

  13. Sun J, Chen LJ, Zhang GB, Jiang JT, Zhu M, Tan Y, et al. Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma. Cancer Immunol Immunother. 2010;59:1163–71.

    Article  PubMed  CAS  Google Scholar 

  14. Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X, et al. Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res. 2008;14:5150–7.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang G, Xu Y, Lu X, Huang H, Zhou Y, Lu B, et al. Diagnosis value of serum B7-H3 expression in non-small cell lung cancer. Lung Cancer. 2009;66:245–9.

    Article  PubMed  Google Scholar 

  16. Tran CN, Thacker SG, Louie DM, Oliver J, White PT, Endres JL, et al. Interactions of T cells with fibroblast-like synoviocytes: role of the B7 family costimulatory ligand B7-H3. J Immunol. 2008;180:2989–98.

    PubMed  CAS  Google Scholar 

  17. Trabattoni D, Saresella M, Pacei M, Marventano I, Mendozzi L, Rovaris M, et al. Costimulatory pathways in multiple sclerosis: distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease. J Immunol. 2009;183:4984–93.

    Article  PubMed  CAS  Google Scholar 

  18. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–7.

    Article  PubMed  CAS  Google Scholar 

  19. Kennedy PG. Viral encephalitis. J Neurol. 2005;252:268–72.

    Article  PubMed  Google Scholar 

  20. Kurtzke JF. Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–52.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang G, Wang J, Kelly J, Gu G, Hou J, Zhou Y, et al. B7-H3 augments the inflammatory response and is associated with human sepsis. J Immunol. 2010;185:3677–84.

    Article  PubMed  CAS  Google Scholar 

  22. Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C. Characterization of mouse and human B7-H3 genes. J Immunol. 2002;168:6294–7.

    PubMed  CAS  Google Scholar 

  23. Xu H, Cheung IY, Guo HF, Cheung NK. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res. 2009;69:6275–81.

    Article  PubMed  CAS  Google Scholar 

  24. Chen X, Zhang G, Li Y, Feng X, Wan F, Zhang L, et al. Circulating B7-H3 (CD276) elevations in cerebrospinal fluid and plasma of children with bacterial meningitis. J Mol Neurosci. 2009;37:86–94.

    Article  PubMed  Google Scholar 

  25. Xu L, Zhang G, Zhou Y, Chen Y, Xu W, Wu S, et al. Stimulation of B7-H3 (CD276) directs the differentiation of human marrow stromal cells to osteoblasts. Immunobiology. 2011;216:1311–7.

    Article  PubMed  CAS  Google Scholar 

  26. Suh WK, Wang SX, Jheon AH, Moreno L, Yoshinaga SK, Ganss B, et al. The immune regulatory protein B7-H3 promotes osteoblast differentiation and bone mineralization. Proc Natl Acad Sci. 2004;101:12969–73.

    Article  PubMed  CAS  Google Scholar 

  27. Stanciu LA, Bellettato CM, Laza-Stanca V, Coyle AJ, Papi A, Johnston SL. Expression of programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by respiratory syncytial virus and type 1 and 2 cytokines. J Infect Dis. 2006;193:404–12.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grants: 81001337, 30930085, 31170834 and 30801023), the Research and Innovation Project for College Graduates of Jiangsu Province (Grant: CXLX11_0077), Scientific Project of Jiangsu Health Department (Grant: H200961) and Science and Technology Support Program of Suzhou City (Grant: SS201246).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Medical Biotechnology, Medical College of Soochow University, Suzhou, Jiangsu, 215007, China

    Juean Jiang, Li Gao, Yongjing Chen, Ranran Zhu, Ting Wang, Fengmin Wang & Xueguang Zhang

  2. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, No.708 Renmin Road, Suzhou, Jiangsu, 215007, China

    Cuiping Liu, Guangbo Zhang & Xueguang Zhang

  3. Department of Special Requirements Ward, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China

    Juean Jiang

  4. Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China

    Jianhua Jiang & Qun Xue

  5. Testing Center, Center for Disease Prevention and Control, Changzhou, Jiangsu, 213000, China

    Fengmin Wang

Authors
  1. Juean Jiang
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  2. Jianhua Jiang
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  3. Cuiping Liu
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  4. Guangbo Zhang
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  5. Li Gao
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  6. Yongjing Chen
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  7. Ranran Zhu
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  8. Ting Wang
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  9. Fengmin Wang
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  10. Xueguang Zhang
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  11. Qun Xue
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Corresponding authors

Correspondence to Xueguang Zhang or Qun Xue.

Additional information

Juean Jiang and Jianhua Jiang contributed equally to the manuscript.

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Jiang, J., Jiang, J., Liu, C. et al. Enhancement of Membrane B7-H3 Costimulatory Molecule but Reduction of Its Soluble Form in Multiple Sclerosis. J Clin Immunol 33, 118–126 (2013). https://doi.org/10.1007/s10875-012-9800-2

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  • DOI: https://doi.org/10.1007/s10875-012-9800-2

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