Are HLA class II and immunoglobulin constant region genes involved in the pathogenesis of mixed cryoglobulinemia type II after hepatitis C virus infection?
OBJECTIVE
Hepatitis C virus infection is known to play an important role in the pathogenesis of essential mixed cryoglobulinemia type II. Progression of hepatitis C virus infection to mixed cryoglobulinemia may be influenced by host immune response. To analyze the immunogenetic background of mixed cryoglobulinemia, we studied HLA-DR, DQ loci and the switch regions of immunoglobulin heavy chain gamma1 and gamma4 constant genes.


METHODS
HLA typing was performed in 84 hepatitis C virus-infected patients (46 with cryoglobulins and 38 without), and 109 healthy controls, through analysis of restriction fragment length polymorphisms, supplemented with other techniques. Immunoglobulin heavy chain gamma1 and gamma4 polymorphisms, detected by restriction fragment length polymorphisms, were studied in 41 patients with mixed cryoglobulinemia and 51 controls.


RESULTS
The gene frequency of DRB1*11 was significantly higher in patients with mixed cryoglobulinemia than in controls (0.36 and 0.20, respectively; p= 0.0035). However, DRB1*11 was also increased in the subgroup of patients without mixed cryoglobulinemia who did not develop severe liver disease, while it was decreased in those with severe liver damage (0.50 and 0.13; p=0.0035). The frequency of 5.4 kb allele of the immunoglobulin heavy chain gamma1 switch region was higher in patients with mixed cryoglobulinemia than in controls (0.47 and 0.22; pc=0.002), while the frequency of 5.5 kb allele was lower (0.51 and 0.78; pc= 0.001).


CONCLUSIONS
Susceptibility to develop cryoglobulins after hepatitis C virus infection was not associated with HLA-DR or DQ. HLA-DRB1*11-positive individuals were protected from serious chronic liver disease after hepatitis C virus infection. Immunoglobulin heavy chain constant gamma1 switch region restriction fragment length polymorphisms were associated with mixed cryoglobulinemia.
Servizio di Genetica, IRCCS Burlo Garofolo and Università di Trieste, Italy. amoroso@burlo.trieste.it
A
A
Amoroso
M
M
Berrino
L
L
Canale
M
M
Cornaglia
S
S
Guarrera
G
G
Mazzola
S
S
Savoldi
F
F
Scolari
M
M
Sällberg
M
M
Clementi
A
A
Gabrielli
D000328:Adult; D000368:Aged; D003449:Cryoglobulinemia / Q000209:etiology* / Q000276:immunology; D003450:Cryoglobulins / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D016174:Hepacivirus / Q000737:chemistry / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D014764:Viral Proteins
D003450:Cryoglobulins; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D014764:Viral Proteins