Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis.
HLA alleles are known to be associated with susceptibility to develop autoimmune hepatitis (AH), and hepatitis A virus (HAV) infection is postulated as a putative trigger for AH. We investigated whether HLA may influence the outcome of the HAV infection by studying 67 children with self-limited and 39 children with protracted forms of this infection. HLA typing of the uncomplicated forms showed no significant increase of any HLA class I or II alleles. In contrast, DRB1*1301 was present in 46.1% of the children with protracted forms (vs. 9.8% in healthy controls; relative risk [RR]: 7.6; chi(2) = 33.3; P = 2 x 10(-9)). In uncomplicated hepatitis, 45% developed anti-smooth muscle antibody (SMA)/actin antibodies, but only 1 child had detectable antibodies after 3 months of infection onset. In contrast, after 1 year, 69% of the patients suffering protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40 and 1:160. Within their follow-up, 2 patients developed a Hashimoto's thyroiditis, but the remaining patients showed no signs of developing autoimmune hepatitis. We conclude that the DRB1*1301 haplotype is strongly associated with the protracted forms of HAV infection and suggest that the infection allows a sustained release of liver self-antigens. However, other still-unknown susceptibility genes are required for the full development of pediatric AH.
Fainboim
L
L
División Inmunogenogenética, Hospital de Clínicas, and Departmento de Microbiología e Immunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina. inmuno@fmed.uba.ar
Cañero Velasco
M C
MC
Marcos
C Y
CY
Ciocca
M
M
Roy
A
A
Theiler
G
G
Capucchio
M
M
Nuncifora
S
S
Sala
L
L
Zelazko
M
M
D000208:Acute Disease; D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006506:Hepatitis A / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans
D015415:Biomarkers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains