The Kunkel legacy and hepatitis C virus infection.

In commemoration of Henry Kunkel's 100th birthday, the effect of his legacy on the investigation of hepatitis C virus is recounted. The delineation of a major cross-idiotype (WA) among patients with essential mixed cryoglobulinemia led to the discovery that HCV was the etiologic agent for this disease. Studies of the cryoglobulins led to the discovery that WA RF reacted specifically with HCV-VLDL like particles that on electronmicroscopy and binding studies appeared to be the virion within a lipid shell.

Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryoglobulinemic vasculitis and B cell malignancies.

Objective: An uncommon manifestation of hepatitis C virus (HCV) infection is systemic vasculitis associated with type II cryoglobulinemia (cryoglobulinemic vasculitis), a proliferative B cell disorder that transforms into B cell malignancy in 5-10% of patients. The monoclonal rheumatoid factors (mRF) that bear the WA cross-idiotype (Xid) are responsible for most cases of cryoglobulinemic vasculitis in patients with HCV infection. The purpose of this study was to determine whether WA B cells can be detected in asymptomatic patients with HCV infection, using sequence analysis of B cell clonal expansions (BCEs) to identify the WA Xid.

Observations on cryoglobulin testing: I. The association of cryoglobulins containing rheumatoid factors with manifestation of cryoglobulinemic vasculitis.

Objective: To investigate the results of mixed cryoglobulin tests performed on patients with and without hepatitis C virus (HCV) infection, to determine whether type II cryoglobulins containing rheumatoid factor (Type II-RF) were associated with cryoglobulinemic vasculitis.

Methods: The cryoglobulin test protocol differed from the routine protocol. In addition to determination of both cryoglobulin concentration and immunoglobulin composition, the presence or absence of RF concentrated in the cryoglobulins was determined.

Observations on cryoglobulin testing: II. The association of oligoclonal mixed cryoglobulinemia with cirrhosis in patients infected with hepatitis C virus.

Objective: To determine whether a mixed cryoglobulin type correlated with cirrhosis in patients infected with hepatitis C virus (HCV).

Methods: We investigated the results of mixed cryoglobulin tests performed in the clinical laboratory on patients with and without HCV infection.

Results: A higher prevalence of oligoclonal cryoglobulins designated Type IIa was present in HCV-infected patients with cirrhosis than in those without cirrhosis.