Surrogate Markers for Antimitochondrial Antibody-Negative Primary Biliary Cholangitis

New Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) has been reported by Reig et al as potential biomarkers in primary biliary cholangitis (PBC). They also reported changes of these antibodies over time, and described the association with clinical outcomes. The authors found that anti-HK1 and anti-KLHL12 were positive in 46.1% and 22.8% of patients, respectively, and changed overtime in 13.3% and 5.5% of patients, respectively. Interestingly, anti-HK1 or antiKLHL12 antibodies were detected in 6 (37.5%) of the 16 patients with antimitochondrial antibody (AMA), and in 4 (40%) of the 10 AMA, anti-gp210– and anti-sp100–seronegative patients. Moreover, a lower response to ursodeoxycholic acid was observed in antiHK1–positive patients according only to Toronto criteria (74% vs 87%, P , 0.02). It is well known that antinuclear antibodies (ANA) demonstrated high PBC specificity and high diagnostic value in AMA-negative PBC patients, particularly the anti-sp100 and anti-gp210 antibodies corresponding to the immunofluorescence PBC-specific ANA patterns of multiple nuclear dots (MND) and rim-like membranous (RL/M), respectively. It would therefore be relevant to test the new antibodies described by Reig et al. in multicenter studies in different geographical areas on a subgroup of patients who are negative for both AMA and all ANAs as detected by immunofluorescence and/or by immunoenzymatic assays with recombinant antigens.