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The Pivotal Role of C1qR in Mixed Cryoglobulinemia

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HCV Infection and Cryoglobulinemia

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Abstract

Non-enveloped HCV core protein, a constitutive antigen component of cryoglobulins in HCV-infected patients, is required for generating cryoglobulin-mediated tissue injury in vivo upon engagement of the globular domain of C1q receptor (gC1qR). gC1qR is proteolytically cleaved from the cell surface, suggesting that the cleavage event is physiologically relevant. Circulating gC1qR may affect numerous aspects of cell biology via intracellular and extracellular pathways. Higher serum levels of gC1qR in mixed cryoglobulinemia indicate that this protein plays a relevant role in the pathogenesis of cryoglobulin-related damage, including immune complex formation and cryoprecipitation.

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References

  1. Saadoun D, Rosenzwajg M, Landau D et al (2008) Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis. Blood 111(11):5334–5341

    Article  PubMed  CAS  Google Scholar 

  2. Sansonno D, Lauletta G, Nisi L et al (2003) Non-enveloped HCV core protein as constitutive antigen of cold-precipitable immune complexes in type II mixed cryoglobulinaemia. Clin Exp Immunol 133(2):275–282

    Article  PubMed  CAS  Google Scholar 

  3. Sabile A, Perlemuter G, Bono F et al (1999) Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates. Hepatology 30:1064–1076

    Article  PubMed  CAS  Google Scholar 

  4. Kurtz JB, Boxall F, Qusir N et al (2001) The diagnostic ­significance of an assay for ‘total’ hepatitis C core antigen. J Virol Methods 96:127–132

    Article  PubMed  CAS  Google Scholar 

  5. Gorevic PD, Frangione B (1991) Mixed cryoglobulinemia cross-reactive idiotypes. Implications for the relationship of MC to rheumatic and lymphoproliferative diseases. Semin Hematol 28:79–94

    PubMed  CAS  Google Scholar 

  6. Lindahl G, Sjobring U, Johnsson E (2000) Human complement regulators: a major target for pathogenic microorganisms. Curr Opin Immunol 12:44–51

    Article  PubMed  CAS  Google Scholar 

  7. Kittlesen DJ, Chianese-Bullock KA, Yao ZQ et al (2000) Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J Clin Invest 106:1239–1249

    Article  PubMed  CAS  Google Scholar 

  8. Yao ZQ, Nguyen DT, Hiotellis AI et al (2001) Hepatitis C core protein inhibits human T lymphocyte responses by a complement-dependent regulatory pathway. J Immunol 167:5264–5272

    PubMed  CAS  Google Scholar 

  9. Dammacco F, Sansonno D, Piccoli C et al (2000) The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinaemia, and overt B-cell malignancy. Semin Liver Dis 20:143–145

    Article  PubMed  CAS  Google Scholar 

  10. Yao Z-Q, Prayter D, Trabue C et al (2008) Differential regulation of SOCS-1 sognalling in B and T lymphocytes by hepatitis C virus core protein. Immunology 2:197–207

    Article  Google Scholar 

  11. Lim BL, Reid KBM, Ghebrehiwet B et al (1996) The binding for globular heads of complement C1q, gC1qR. Functional expression and characterization as a novel vitronectin binding factor. J Biol Chem 271:26739–26744

    Article  PubMed  CAS  Google Scholar 

  12. Sansonno D, Cornacchiulo V, Iacobelli AR et al (1995) Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus-infected patients with mixed cryoglobulinaemia. Hepatology 21:305–312

    PubMed  CAS  Google Scholar 

  13. Sansonno D, Gesualdo L, Monno C et al (1997) Hepatitis C virus-related proteins in kidney tissue from hepatitic C virusinfected patients with cryoglobulinemic membranoproliferative glomerulonephritis. Hepatology 25:1237–1244

    Article  PubMed  CAS  Google Scholar 

  14. Ghebrehiwet B, Lim B-L, Kumar L et al (2001) gC1q-R/p33: a member of a new class of multifunctional and multicompartimental cellular proteinsis involved in inflammation and infection. Immunol Rev 180:65–77

    Article  PubMed  CAS  Google Scholar 

  15. Joseph K, Ghebrehiwet B, Peerschke EI et al (1996) Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular “heads” of C1q (gC1q-R). Proc Natl Acad Sci U S A 93:8552–8557

    Article  PubMed  CAS  Google Scholar 

  16. Lim BL, Reid KBM, Ghebrehiwet B et al (1996) The binding protein for globular heads of complement C1q, gC1qR. Functional expression and characterization as a novel vitronectin binding factor. J Biol Chem 271:26739–26744

    Article  CAS  Google Scholar 

  17. Paul DB, Kuhns MC, McNamara AL et al (1995) Short-term stability of HIV provirus levels in the peripheral blood of HIV-infected individuals. J Med Virol 47:292–297

    Article  PubMed  CAS  Google Scholar 

  18. Simos G, Georgatos SD (1994) The lamin B receptor-associated protein p34 shares sequence homology and antigenic determinants with the splicing factor 2-associated protein p32 [letter]. FEBS 346:225–228

    Article  CAS  Google Scholar 

  19. Krainer AR, Mayeda A, Kozak D et al (1991) Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70 K, and drosophila splicing regulators. Cell 66:383–394

    Article  PubMed  CAS  Google Scholar 

  20. Seytter T, Lottspeich F, Neupert W et al (1998) Mam33p, an oligomeric, acidic protein in the mitochondrial matrix of Saccharomyces cerevisiae is related to the human complement receptor gC1q-R. Yeast 14(4):303–310

    Article  PubMed  CAS  Google Scholar 

  21. Sunayama J, Ando Y, Itoh N et al (2004) Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore forming protein p32. Cell Death Differ 11:771–781

    Article  PubMed  CAS  Google Scholar 

  22. Matthews DA, Russell WC (1998) Adenovirus core protein V interacts with p32 a protein which is associated with both the mitochondria and the nucleus. J Gen Virol 79:1677–1685

    PubMed  CAS  Google Scholar 

  23. Luo Y, Yu H, Peterlin BM (1994) Cellular protein modulates effects of human immunodeficiency virus type I Rev. J Virol 68:3850–3856

    PubMed  CAS  Google Scholar 

  24. Joseph K, Ghebrehiwet B, Kaplan A-P (2001) Activation of the kininforming cascade on the surface of endothelial cells. Biol Chem 382:71

    Article  PubMed  CAS  Google Scholar 

  25. Peerschke EI, Ghebrehiwet B (1988) Identification and partial characterization of human platelet C1q binding sites. J Immunol 141(10):3505–3511

    PubMed  CAS  Google Scholar 

  26. Jiang J, Zhang Y, Krainer AR et al (1999) Crystal structure of human p32, a doughnut-shaped acidic mitochondrial matrix protein. Proc Natl Acad Sci USA 96(7):3572–3577

    Article  PubMed  CAS  Google Scholar 

  27. Zlatarova AS, Rouseva M, Roumenina LT et al (2006) Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. Biochemistry 45(33):9979–9988

    Article  PubMed  CAS  Google Scholar 

  28. Gaboriaud C, Jaunhuix J, Gruez A et al (2003) The crystal structure of globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem 278:46974–46982

    Article  PubMed  CAS  Google Scholar 

  29. Sansonno D, Dammacco F (2005) Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis 5(4):227–236

    Article  PubMed  Google Scholar 

  30. Frank MM (1995) Animal models for complement deficiencies. J Clin Immunol 15(6 Suppl):113S–121S

    Article  PubMed  CAS  Google Scholar 

  31. Fujita T, Gigli I, Nussenzweig V (1978) Human C4-binding protein II: role in proteolysis of C4b by C3b-inactivator. J Exp Med 148(4):1044–1051

    Article  PubMed  CAS  Google Scholar 

  32. Okroj M, Heinegård D, Holmdahl R et al (2007) Rheumatoid arthritis and the complement system. Ann Med 39(7):517–530

    Article  PubMed  CAS  Google Scholar 

  33. Sansonno D, Tucci FA, Ghebrehiwet B et al (2009) Role of the receptor for the globular domain of C1q protein in the pathogenesis of hepatitis C virus-related cryoglobulin vascular damage. J Immunol 183(9):6013–6020

    Article  PubMed  CAS  Google Scholar 

  34. Waggoner SN, Hall CH, Hahn YS (2007) HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. J Leukoc Biol 82(6):1407–1419

    Article  PubMed  CAS  Google Scholar 

  35. Peerschke EI, Ghebrehiwet B (1998) Platelet receptors for the complement component C1q: implications for hemostasis and thrombosis. Immunobiology 199(2):239–249

    Article  PubMed  CAS  Google Scholar 

  36. Nickelet V, Mihatsch NJ (2003) Kidney transplants, antibodies and rejection: is C4d a magic marker? Nephrol Dial Transplant 18(11):2232–2239

    Article  Google Scholar 

  37. Peerschke EI, Ghebrehiwet B (2007) The contribution of gC1qR/p33 in infection and inflammation. Immunobiology 212(4–5):333–342

    Article  PubMed  CAS  Google Scholar 

  38. Ghebrehiwet B, Cebada Mora C, Tantral L et al (2006) gC1qR/p33 serves as a molecular bridge between the complement and contact activation systems and is an important catalyst in inflammation. Adv Exp Med Biol 586:95–105

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Sciences and Clinical Oncology, University of Bari Medical School, Bari, Italy

    Domenico Sansonno & Franco Dammacco

  2. Laboratory of Genetics, Department of Biomedical Sciences, University of Foggia Medical School, Foggia, Italy

    Loredana Sansonno

Authors
  1. Domenico Sansonno
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  2. Loredana Sansonno
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  3. Franco Dammacco
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Correspondence to Domenico Sansonno .

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Editors and Affiliations

  1. , Department of Internal Medicine and Clin, University of Bari, Piazza Giulio Cesare 11, Bari, 70124, Italy

    Franco Dammacco

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Sansonno, D., Sansonno, L., Dammacco, F. (2012). The Pivotal Role of C1qR in Mixed Cryoglobulinemia. In: Dammacco, F. (eds) HCV Infection and Cryoglobulinemia. Springer, Milano. https://doi.org/10.1007/978-88-470-1705-4_11

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  • DOI: https://doi.org/10.1007/978-88-470-1705-4_11

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  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-1704-7

  • Online ISBN: 978-88-470-1705-4

  • eBook Packages: MedicineMedicine (R0)

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