TY - JOUR
T1 - Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis
AU - Marcos, Yanina
AU - Fainboim, Hugo A.
AU - Capucchio, Mónica
AU - Findor, Jorge
AU - Daruich, Jorge
AU - Reyes, Beatriz
AU - Pando, Marcelo
AU - Theiler, Graciela del C
AU - Méndez, Nora
AU - Satz, M. Leonardo
AU - Fainboim, Leonardo
PY - 1994/6
Y1 - 1994/6
N2 - We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlympho-cytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; χ2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; χ2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (χ2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found. Interestingly, in autoimmune chronic active hepatitis of childhood (in which extrahepatic manifestations are seldom observed) a strong association with human leukocyte antigen DR6 was recently observed in patients from the same ethnic group and geographic region. The clinical and genetic heterogenity observed in this study may explain the weak human leukocyte antigen associations reported previously for autoimmune chronic active hepatitis and suggest that the extrahepatic forms in patients with autoimmune chronic active hepatitis represents a separate clinical entity.
AB - We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlympho-cytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; χ2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; χ2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (χ2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found. Interestingly, in autoimmune chronic active hepatitis of childhood (in which extrahepatic manifestations are seldom observed) a strong association with human leukocyte antigen DR6 was recently observed in patients from the same ethnic group and geographic region. The clinical and genetic heterogenity observed in this study may explain the weak human leukocyte antigen associations reported previously for autoimmune chronic active hepatitis and suggest that the extrahepatic forms in patients with autoimmune chronic active hepatitis represents a separate clinical entity.
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M3 - Article
C2 - 8188167
SN - 0270-9139
VL - 19
SP - 1371
EP - 1374
JO - Hepatology
JF - Hepatology
IS - 6
ER -