Autoimmune hepatitis in childhood: The role of genetic and immune factors

Table 1 Autoantibodies studies and their findings

Type of AIH	Autoantibodies	Antigen	Meaning
AIH type 1	Anti-actin	Actin	Poor response to treatment with corticosteroids[19-21]
AIH types 1 and 2 (80%-90% of cases)	Anti-asialoglycoprotein receptor	Asialoglycoprotein receptor	Liver specific antigen and indicative of prognosis[22,23]
AIH types 1 and 2 (8%-20% of cases)	Antimitochondrial antibody-M2	Mitochondria	Favorable response to corticosteroids[24,25]
AIH type 1 (39% of cases)	Anti-chromatin	Chromatin	High titers of immunoglobulin G and shows disease activity[26,27]
AIH type 2 (32% of cases)	Anti-liver-cytosol type 1	Enzyme formiminotransferase cyclodeaminase	Diagnostic tool and marker of liver inflamation[28-30]
AIH type 1	Antibody to histone and dsDNA	dsDNA	High titers of immunoglobulin G and poor-immediate response to corticosteroids[26]
AIH type 1 (47.5% of cases)	Anti-soluble liver antigen	t-RNAs	Presence of severe forms, associated with fatal outcome[31-35]
AIH type 2 (5%-19% of cases)	LKM-3	Uridinediphosphateglucuronyltranferase	Allows diagnosis, being sometimes the only marker identified[36]
AIH type 1	Perinuclear antinuclear neutrophil cytoplasmic antibodies	Peripheral nuclear and perinuclear antigen	Presence of severe forms;
			Most frequent in primary sclerosing cholagitis and primary biliary cirrhosis[36-38]

AIH: Autoimmune hepatitis; dsDNA: Double-stranded DNA.

Table 2 Major histocompatibility complex class II human leukocyte antigen and its association with autoimmune hepatitis patients

Ref.	Total No. of patients/controls (No. of children)	What was evaluated	Conclusions
Donaldson et al[48]	96/100 (no)	HLA-DR	HLA-DR3 and DR4 genes independently confer susceptibility to autoimmune hepatitis
Fortes Mdel et al[50]	41/111 (13)	HLA-A, -B, -C, -DR and DQ	Regarding HLA-A and -C there were no significant differences between groups; For HLA class I, an increase in the frequency of B*08, B*18, B*45 and B*50 was observed. HLA B*40 was more frequent in healthy controls; For HLA class II, an increase in the frequency of HLA-DQB1*02, -DQB1*04, HLA-DRB1*03, DRB1*13 and DRB3 was observed. HLA-DRB1*1301 and -DRB1*0301 were more frequent in children
Ota et al[51]	51/no (no)	HLA-DR and -DQ	Increased frequency of all HLA-DRB1*04 alleles, principally -DRB1*0405. Secondary association with -DRB1*15 and DRB1*16
Vázquez-García et al[52]	30/175 (not cited)	HLA-A, -B, -C, -DR and -DQ	A significant association with HLA-DRB1*0404 was found. It was present in patients with average age onset. DQB1*0301 had a low frequency in patients and may represent a protective factor; No association was found with any class I antigen
Fainboim et al[53]	52/197 (all)	HLA-A, -B, -C, -DR and -DQ	No significant associations with HLA class I antigens were found; HLA-DR6 group (HLA-DRB1) showed increased frequency, principally HLA-DRB1*1301; The analyses of HLA-DQ group showed an associations of HLA-DQB1*0603
Pando et al[54]	206/208 (122)	HLA-DR and -DQ	The frequencies of HLA-DRB1*1301, -DRB1*0301, -DQA1*0103, -DQB1*0603 were significantly increased on AIH patients; HLA-DRB1*1301 was associated with younger age at disease onset, being the allele associated with AIH in children and HLA-DRB1*1302 worked as a protective factor
Bittencourt et al[55]	139/129 (74)	HLA-DRB and -DQB1	In AIH type 1, there was significant increase in the HLA-DRB1*13, -DRB1*03, -DRB3 and -DQB1*06 alleles in patients. HLA-DRB1*13 was more frequent in children than adults. The low frequency of HLA-DQB1*0301 may indicate a protective role of this allele; In AIH type 2, a significant increase in DRB1*07, DRB1*03, DRB4 and DQB1*02 was observed
Czaja et al[56]	86/102 (not cited)	HLA-A, -B, -C, -DR and -DQ	DRB4*0103 is associated with immune diseases, DRB1*0301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation
Czaja et al[57]	210/396 controls with other chronic liver disease/102 healthy controls (no)	HLA-DR B1*03, -DRB1*04 and -DRB1*13	The frequency of HLA DRB1*13 was higher in patients without -DRB1*03 and -DRB1*04; Primary sclerosing cholangite patients showed a similar frequency of HLA-DRB1*13 when compared with AIH patients

HLA: Human leukocyte antigen; MHC: Major histocompatibility complex; AIH: Autoimmune hepatitis.