Hepatitis C virus (HCV)-driven stimulation of subfamily-restricted natural IgM antibodies in mixed cryoglobulinemia

Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity

“…As a matter of fact, it is often possible to evidence cold-precipitable immunoglobulins (cryoglobulins) in patients infected by HCV. In particular, cold-precipitable immunoglobulins have been described as belonging to VH1-69 subfamily, elicited by HCV infection, in complex with IgMs belonging to VH3-23 and VH3-21 Ab subfamilies [50,51]. Briefly, VH1-69 antibodies expansion drives the formation of precipitates due to VH1-69 Abs natural recognition by VH3-23 and VH3-21 IgMs (probably due to the peculiar abundance of hydrophobic amino acid residues in VH1-69 Abs) [52].…”

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

“…As an example, in several studies the use of phage display technology allowed the selection of distinct autoreactive Abs which were further characterized in terms of Ag specificity and biological activity [75]. These studies demonstrated that the VH and VL sequences of the cryoprecipitable monoclonal IgM match those of the IgV genes of monoclonal B cells isolated from patients with MCII [55, 76].…”

“…B cell mono/oligoclonal expansion of clones expressing VH subfamily gene segments other than VH1-69, such as VH3-7, VH3-21, VH3-23, VH3-30, VH4-34, VH3-48, and VH4-59, seems to be implicated in HCV-related lymphoproliferative disorders [75, 77, 100]. Moreover, as in the case of VH1-69, monoclonal expansion of B-cell clones expressing most of these VH subfamilies is a common feature of a wide variety of autoimmune disorders and lymphomas [75, 100, 101, 108].…”

Occult Hepatitis C Infection and its Clinical Relevance in Lymphoproliferative Disorders

“…A productive VH1-69 rearrangement is present in 1.6% of normal B lymphocytes in adults. However, VH1-69 is rearranged in 10% to 20% of B-cell chronic lymphocytic (Perotti et al, 2008).…”