The Prevalence of Anti-Hexokinase-1 and Anti-Kelch-Like 12 Peptide Antibodies in Patients With Primary Biliary Cholangitis Is Similar in Europe and North America: A Large International, Multi-Center Study

Abstract

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is present worldwide. Autoantibodies, in particular anti-mitochondrial antibodies (AMA) detected by indirect immunofluorescence assays or newer solid phase immunoassays can detect most, but not all individuals with PBC. Detection of antibodies to the anti-nuclear antigens sp100 and gp210 can identify additional PBC patients, but some seronegative patients remain, often resulting in delayed diagnosis and treatment. Antibodies to kelch-like 12 (KLHL12) and hexokinase 1 (HK-1) were recently identified as new biomarkers for PBC and notably identify patients who are negative for conventional autoantibodies. To become globally adopted, it is important to validate these new biomarkers in different geographic areas. In the present study we evaluated the prevalence of anti-KLHL12 (measured by a KLHL12-derived peptide referred to as KL-p) and anti-HK-1 antibodies by ELISA at five sites within Europe and North America and demonstrated the presence of these antibodies in patients with PBC in all geographies.

Anti-Mitochondrial Antibody Titers Decrease Over Time in Primary Biliary Cholangitis Patients With Ursodeoxycholic Acid Therapeutic Response: A Cohort Study Followed Up to 28 Years

“…Third, since a liver biopsy was not performed for most patients to confirm liver cirrhosis, the diagnosis of cirrhosis might have not been optimal in some patients. Fourth, PBC-specific antinuclear antibodies (ANAs) including anti-sp100 and anti-gp210 ( 1 ), or antibodies to kelch-like 12 (KLHL12) and hexokinase 1 (HK-1) ( 39 ) might aid to diagnosis the AMA-negative PBC, correlate the prognosis and AMA-associated results of PBC patients. However, these autoantibodies were not assessed in most labs in Taiwan, and the associated data thus are not available in in the current study.…”

Establishment of international autoantibody reference standards for the detection of autoantibodies directed against PML bodies, GW bodies, and NuMA protein

“…HK1 is a mitochondrial enzyme that regulates crucial cellular processes [52]. Anti-HK1 and anti-KLHL 12 have been reported as novel biomarkers for PBC patients [49,51,53], although their specificity to PBC have not been validated [50]. Cytoplasmic discrete dots/GWB-like pattern (AC-18) are associated with antibodies to GW182, Ge-1, and Su/ Ago2.…”

Working Algorithms and Detection Methods of Autoantibodies in Autoimmune Liver Disease: A Nationwide Study

“…As mentioned above, PBC-specific nuclear antigens have been identified, being Sp100 and gp210 the major target antigens. New serological markers recently associated with PBC (anti-hexokinase-1 and anti-kelch-like-protein-12 autoantibodies [10,11]) have not been studied in this workshop due to the fact that currently there are no available CE-marked kits on the market.…”

“…The main targets for those ANAs are anti-Sp100 and anti-gp210 autoantibodies. Recently, PBC has also been associated with the presence of anti-hexokinase-1 and anti-kelch-like-protein-12 autoantibodies [10,11]. The sensitivity and specificity characteristics of the different autoantibodies described above, in terms of the clinical relevance of their presence or absence in the diagnosis of the disease, as well as their different immunofluorescence patterns, are shown in Table 1 and Figure 1.…”