The ability of the immune system to distinguish between self and non-self is critical to the functioning of the immune response. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied part of the autoimmune process is the human leukocyte antigen (HLA) region. Recently, progress has been made in narrowing down HLA cluster classifications based on structural and functional features of HLA alleles. Using this approach we have investigated 175 patients with hepatitis C virus (HCV)-induced type II cryoglobulinemia (MC), and compared them to a control group of 14,923 bone marrow donors. Additionally, we investigated the frequency of HLA homozygosity in the same groups of subjects. Our results provide evidence of a role for DR5 and DQ3 HLA class II clusters and a higher frequency of HLA homozygous leading to the clinical outcome of type II mixed cryoglobulinemic autoimmune disease. The DR5 cluster is characterized by a Glu in (J9 and its polymorphism is connected with preferred anchors at (J9 of the binding peptide, while the DQ3 cluster is characterized by Glu B86 and Leu B87, which allows the binding of large hydxophobic amino acids at pl of the binding peptide. The mechanisms by which variations in HLA lead to autoimmunity remain unknown, although they are likely to be mediated by continuous presentation of HCV epitopes to T cells and a genetic background that limits the effective clearance of HCV. The results presented in this paper have increased our knowledge of the mechanism of autoimmune disease and B-cell lymphoproliferation during HCV infection.

Genetic insights in to the disease mechanism of type II mixed cryoglobulinemia induced by hepatitis C virus / V. De Re; L. Caggiari L; S. De Vita; C. Mazzaro; M. Lenzi; M. Galli; G. Monti ; C. Ferri; A. L. Zignego; A. Gabrielli ; B. Sansonno; F. Dammacco; M. Libra; N. Sacchi; R. Talamini ; M. Spina M; R. Cannizzaro; M. Guidoboni; R. Dolcetti. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - STAMPA. - 39 S1:(2007), pp. 65-71.

Genetic insights in to the disease mechanism of type II mixed cryoglobulinemia induced by hepatitis C virus.

ZIGNEGO, ANNA LINDA;
2007

Abstract

The ability of the immune system to distinguish between self and non-self is critical to the functioning of the immune response. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied part of the autoimmune process is the human leukocyte antigen (HLA) region. Recently, progress has been made in narrowing down HLA cluster classifications based on structural and functional features of HLA alleles. Using this approach we have investigated 175 patients with hepatitis C virus (HCV)-induced type II cryoglobulinemia (MC), and compared them to a control group of 14,923 bone marrow donors. Additionally, we investigated the frequency of HLA homozygosity in the same groups of subjects. Our results provide evidence of a role for DR5 and DQ3 HLA class II clusters and a higher frequency of HLA homozygous leading to the clinical outcome of type II mixed cryoglobulinemic autoimmune disease. The DR5 cluster is characterized by a Glu in (J9 and its polymorphism is connected with preferred anchors at (J9 of the binding peptide, while the DQ3 cluster is characterized by Glu B86 and Leu B87, which allows the binding of large hydxophobic amino acids at pl of the binding peptide. The mechanisms by which variations in HLA lead to autoimmunity remain unknown, although they are likely to be mediated by continuous presentation of HCV epitopes to T cells and a genetic background that limits the effective clearance of HCV. The results presented in this paper have increased our knowledge of the mechanism of autoimmune disease and B-cell lymphoproliferation during HCV infection.
2007
39 S1
65
71
V. De Re; L. Caggiari L; S. De Vita; C. Mazzaro; M. Lenzi; M. Galli; G. Monti ; C. Ferri; A. L. Zignego; A. Gabrielli ; B. Sansonno; F. Da...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/257420
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