HLA-DRB1*1301 and *1302 protect against chronic hepatitis B.
OBJECTIVE
The outcome of acute hepatitis B infection may be influenced by host factors like the major histocompatibility complex (MHC). We have investigated MHC class I and class II antigens in patients with chronic hepatitis B compared to a healthy control population. To confirm the findings of this first study we performed a second study in a group of subjects who had spontaneously recovered from acute hepatitis B infection.


METHODS
Frequencies of MHC class I and class II antigens were analyzed in patients with chronic hepatitis B virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotypes were determined by polymerase chain reaction based typing methods.


RESULTS
In the first study the class II allele HLA-DRB1*1301-02 was found in 4 of 70 subjects with chronic hepatitis B virus infection (5.7%) compared to 27 of 101 healthy controls (26.7%, relative risk 0.17; p=0.001; p(corr)=0.025). This protective effect of the DRB1*1301-02 allele was confirmed in the second study. Eight of 24 patients (33.3%) who cleared hepatitis B virus spontaneously were positive for DRB1*1301-02 (relative risk of developing chronic infection compared to chronic hepatitis B subjects 0.12; p=0.004). Subtyping confirmed that 1301 and 1302 were both decreased in frequency in patients with chronic hepatitis B.


CONCLUSIONS
The MHC class II allele DRB1* 1301-02 is associated with protection from chronic hepatitis B in Caucasian patients.
Höhler
T
T
I. Department of Internal Medicine, Johannes Gutenberg University Mainz, Germany.
Gerken
G
G
Notghi
A
A
Lubjuhn
R
R
Taheri
H
H
Protzer
U
U
Löhr
H F
HF
Schneider
P M
PM
Meyer zum Büschenfelde
K H
KH
Rittner
C
C
D000328:Adult; D000483:Alleles; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006509:Hepatitis B / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012075:Remission, Spontaneous; D012698:Serologic Tests
D004279:DNA, Viral; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G