P. Schott et al., IN-VITRO REACTIVITY OF CRYOGLOBULIN IGM AND IGG IN HEPATITIS-C VIRUS-ASSOCIATED MIXED CRYOGLOBULINEMIA, Journal of hepatology, 28(1), 1998, pp. 17-26
Background/Aims: Mixed cryoglobulinemia is frequently associated with
chronic hepatitis C virus infection. We aimed to clarify the mechanism
, kinetics and participating proteins in cryoprecipitate formation, wh
ich are still being debated, Methods: Eighteen patients with cryoglobu
linemia were studied, Isolated serum cryoprecipitates and purified cry
oglobulin IgM and IgG fractions were analyzed in vitro by turbidimetry
for temperature-dependent complex formation, Immunoglobulin reactivit
y, i.e. in cryoprecipitates and in cryoglobulin-free sera, was studied
using immunoblot and enzyme immunoassays. HCV RNA was detected by rev
erse transcriptase/polymerase chain reaction, Results: By turbidimetry
, purified cryo-IgM precipitated (in the absence of HCV RNA) with cryo
-IgG as well as with non-cryoglobulin IgG and with IgG Fc or F(ab')(2)
fragments, In contrast, purified cryo-IgG did not precipitate with no
n-cryoglobulin IgM, Anti-HCV IgG reactivity was found in cryoglobulin-
free sera, in cryoprecipitates and in purified cryoglobulin IgG fracti
ons, The respective titers were similar, Purified cryo-IgM did not rea
ct to HCV-encoded proteins. Binding of cryo-IgM to heterologous IgG wa
s inhibited by intact IgG (up to a mean of about 52%) as well as by Ig
G Fc (33%) and F(ab')(2) fragments (17%), Binding of cryo-IgM to IgG w
as enhanced at low temperature (4 degrees C vs. 37 degrees C), particu
larly for type III cryoglobulin IgM. Conclusions: In hepatitis C virus
-associated cryoglobulinemia the in vitro precipitate formation depend
ed on cryo-IgM, while IgG appeared to act as an unspecific antigenic p
artner, Hepatitis C viral particles were probably not required, Cryo-I
gM binding occurred primarily to intact IgG, Anti-HCV reactivity of ei
ther cryo-IgM or cryo-IgG was not necessary for precipitate formation,
Regarding the pathogenesis, a direct hepatitis C virus protein-depend
ent stimulation of B-cells producing cryo-IgM seems to be unlikely.