Human leucocyte antigens and pediatric autoimmune liver disease: diagnosis and prognosis

Abstract

• HLA-DRB1*03 is NOT associated with pediatric AIH in a previous national study. • In other studies, HLA-DRB1*03 is associated with AIH1. • HLA-DRB1*13 is associated with PSC. • HLA-DRB1*04 is described as protective for AILD. What is New: • HLA-DRB1 four-digit typing for all alleles and for all subgroups of pAILD combined with re-assessment of liver histology • HLA-DRB1*03:01 is associated with pediatric AIH1 and AISC. • HLA-DRB1*03:01 appears to be a prognostic marker. • HLA-DRB1*13:01 is associated with pediatric AIH1 in mixed ethnicity cohort. • HLA-DRB1*04 does not show any protective effect for pAILD.

Autoimmune hepatitis: current challenges and future prospects

“…DRB1*1301 is also correlated with child type 1 AIH in Germany 19. In Pakistan, HLA-DR6, DRB1*14, and DRB1*13 were more prevalent in AIH 20…”

Pediatric autoimmune hepatitis shows a disproportionate decline of regulatory T cells in the liver and of IL-2 in the blood of patients undergoing therapy

“…Children with evidence for autoimmune sclerosing cholangitis, replicative viral hepatitis, an AIH score below 10 [20], and any ongoing treatment with immunosuppressive medication during the initial diagnosis of pAIH were excluded from the study (Table 1, S1 Fig) [4]. Additionally, 13 available pAIH follow-up biopsies under therapy between 1996 and 2012 were included.…”

“…Furthermore, the frequencies of the major genetic risk alleles of the MHC class II locus are age dependent. While both HLA-DRB1*03 and *04 predispose to adult manifestations, pAIH is associated with HLA-DRB1*03 and HLA-DRB1*13, relative to the geographical region [2, 4, 5]. …”

Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children

“…The HLA type also seems to be related to the age of presentation especially as DRB1*04 has not been found to predispose patients to developing AIH in childhood (8,11,(17)(18)(19). The different HLA associations in patients with AIH type 1 and type 2 that have been reported in previous literature are shown in Table 1, and this shows that associations between HLA and type 1 and type 2 seem to differ (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). AIH/PSC overlap syndrome in children has been particularly associated with the presence of HLA DRB1*13 (22).…”

“…During the last few decades, it has been demonstrated that there are various HLA associations with AIH and PSC in different geographic areas and among different ethnic groups (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The HLA type also seems to be related to the age of presentation especially as DRB1*04 has not been found to predispose patients to developing AIH in childhood (8,11,(17)(18)(19). The different HLA associations in patients with AIH type 1 and type 2 that have been reported in previous literature are shown in Table 1, and this shows that associations between HLA and type 1 and type 2 seem to differ (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”