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Haplotype HLA-B8-DR3 Confers Susceptibility to Hepatitis C
Virus-Related Mixed Cryoglobulinemia
Marco Lenzi,
Magda Frisoni,
Vilma Mantovani,
Paolo Ricci,
Luigi Muratori,
Raffaella Francesconi,
Mariaclara Cuccia,
Silvio Ferri, and
Francesco B. Bianchi
From Dipartimento di Medicina Interna, Cardioangiologia,
Epatologia, Istituto di Ematologia, Universita di Bologna,
Policlinico S. Orsola, Bologna, Italia; Servizio di Reumatologia,
Laboratorio Centralizzato, Azienda Policlinico S.Orsola Malpighi,
Bologna, Italia; and Dipartimento di Genetica e Microbiologia,
Università di Pavia, Pavia, Italia.
Our aim was to investigate whether host genetic factors are involved
in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia
(MC). We studied 25 consecutive patients presenting with a full-blown
clinical picture of MC by physical examination, blood chemistry,
assessment of cryoglobulins and their composition, nonorgan-specific
autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism.
Biopsies of liver, bone marrow, and minor salivary glands were also
performed in a number of patients. HLA results were compared with those
of normal controls and patients with chronic HCV infection without MC
and negative for autoimmune phenomena (pathological controls). Type II
MC was found in 14 of 25 patients (56%), and type III MC was found in
the remaining 11 (44%). All patients were positive for antibodies to
HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25)
of patients compared with 10.1% (38 of 377) of normal controls
(P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls
(P = .007, Pcorrected = not
significant). As for class II HLA molecules, only DR3 was significantly
more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected
= .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was
calculated in patients positive for B8 and/or DR3, and the
highest OR (8.2) was observed in individuals possessing both. The
results suggest that the development of HCV-related MC is associated
with HLA-B8 and DR3 markers.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2062-2066
© 1998 by The American Society of Hematology.
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