13 If present in high titer, anti-LKM1 strongly support the diagnosis of AIH, even if liver biopsy is precluded by other clinical

considerations. The mainstay technique for autoantibody screening is indirect immunofluorescence on composite sections of freshly frozen rodent stomach, kidney and liver.14 This technique not only permits the detection of ANA, SMA, anti-LKM1, and AMA but also suggests the presence of other autoantibodies of an evolving clinical importance, such as antibody CB-839 in vivo to liver cytosol type 1 (anti-LC1)111,121 and antibody to liver kidney microsome type 3 (anti LKM-3).122,123 Confirmation of the presence of the latter autoantibody is obtained with assays detecting antibodies to their molecular targets, formiminotransferase see more cyclo-deaminase (FTCD) and family 1 UDP-glucuronosyl-transferases (UGT1A), respectively (Table 4). Other autoantibodies that may be useful in classifying patients who lack the conventional serological findings are anti-SLA124-128 and

atypical pANCA.119,129,130,131-139 Atypical pANCA, originally considered specific for PSC and inflammatory bowel disease (IBD),124,125 are frequently present in patients with AIH,126,127 and occasionally can be the only autoantibodies detected (Table 4).128 ANCA typically do not coexist with anti-LKM1.127 Recent evidence indicates that the target of atypical pANCA is located within the nuclear membrane. For this reason, a more suitable designation may be peripheral anti-neutrophil nuclear antibody (pANNA) (Table 4).102,103 Anti-SLA129 and anti–liver-pancreas (anti-LP),130 originally described as separate autoantibodies in AIH, were later found to target the same antigen and to

represent a single serological entity. These antibodies are now referred to as anti-SLA or anti-SLA/LP. Their molecular target is a transfer ribonucleoprotein (Table 4).119,131,132 SLA has recently been renamed SEPSECS (Sep [O-phosphoserine] check details tRNA synthase) Selenocysteine Synthase. Anti-SLA are occasionally found in patients with AIH who are negative for ANA, SMA, and anti-LKM1,133 but are more commonly found in association with the conventional autoantibodies, especially if sensitive immunoassays are used.133-136 Anti-SLA are highly specific for the diagnosis of autoimmune liver disease,133 and their detection may identify patients with more severe disease and worse outcome.137-140 Commercial ELISAs are available for their detection. The conventional and nonstandard autoantibodies described in AIH are shown in Table 4. Figure 4 provides an algorithm for the use of autoantibodies in the diagnosis of AIH. Multiple genetic associations with AIH have been described in different ethnic groups.29,141-154 The primary genetic association is with the major histocompatibility complex locus, and associations of HLA alleles with disease predisposition, clinical phenotype, response to therapy, and outcome have been studied.