Antimitochondrial Antibodies: from Bench to Bedside

Colapietro, Francesca; Lleò, Ana; Generali, Elena

doi:10.1007/s12016-021-08904-y

Cited by 42 publications

(44 citation statements)

References 118 publications

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“…In addition, PDC can also be present in the nucleus catalyzing histone acetylation [ 50 , 51 ]. In turn, PDC-E2 is also the key antigen in primary biliary cholangitis, a chronic liver disease with autoimmune component targeting intrahepatic bile duct lining cells [ 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

A New Role of NAP1L1 in Megakaryocytes and Human Platelets

Freitag

Schwertz

2022

IJMS

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Platelets (PLTs) are anucleate and considered incapable of nuclear functions. Contrastingly, nuclear proteins were detected in human PLTs. For most of these proteins, it is unclear if nuclear or alternatively assigned functions are performed, a question we wanted to address for nuclear assembly protein 1like 1 (NAP1L1). Using a wide array of molecular methods, including RNAseq, co-IP, overexpression and functional assays, we explored expression pattern and functionality of NAP1L1 in PLTs, and CD34+-derived megakaryocytes (MKs). NAP1L1 is expressed in PLTs and MKs. Co-IP experiments revealed that dihydrolipolylysine-residue acetyltransferase (DLAT encoded protein PDC-E2, ODP2) dynamically interacts with NAP1L1. PDC-E2 is part of the mitochondrial pyruvate-dehydrogenase (PDH) multi-enzyme complex, playing a crucial role in maintaining cellular respiration, and promoting ATP-synthesis via the respiratory chain. Since altered mitochondrial function is a hallmark of infectious syndromes, we analyzed PDH activity in PLTs from septic patients demonstrating increased activity, paralleling NAP1L1 expression levels. MKs PDH activity decreased following an LPS-challenge. Furthermore, overexpression of NAP1L1 significantly altered the ability of MKs to form proplatelet extensions, diminishing thrombopoiesis. These results indicate that NAP1L1 performs in other than nucleosome-assembly functions in PTLs and MKs, binding a key mitochondrial protein as a potential chaperone, and gatekeeper, influencing PDH activity and thrombopoiesis.

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Section: Resultsmentioning

confidence: 99%

A New Role of NAP1L1 in Megakaryocytes and Human Platelets

Freitag

Schwertz

2022

IJMS

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“…Currently, NAFLD is the most common liver disease, which is mainly associated with the incidence of metabolic syndrome. During the development of inflammation, NAFLD may evolve to non-alcoholic steatohepatitis (NASH) and eventually to cirrhosis and its complications; however, the involvement of the biliary ducts is rare ( 34 ). Hindi et al.…”

Section: Discussionmentioning

confidence: 99%

Using two-step cluster analysis to classify inpatients with primary biliary cholangitis based on autoantibodies: A real-world retrospective study of 537 patients in China

Zhao

Liao

et al. 2023

Front. Immunol.

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BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

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“…Furthermore, studies showed that a low prevalence of AMA can even be detected in the general population, which varies between 0.16% and 3.8%. [26,27] All of these pieces of evidence emphasize that a caveat in interpreting even a highly sensitive and specific test like AMA for PBC is to take into account the clinical setting and appropriate scenario. Our study had several limitations.…”

Section: Characteristicsmentioning

confidence: 99%

The future risk of primary biliary cholangitis (PBC) is low among patients with incidental anti‐mitochondrial antibodies but without baseline PBC

Duan

Chen

et al. 2022

Hepatol Commun

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Anti‐mitochondrial autoantibodies (AMAs) are highly specific for the diagnosis of primary biliary cholangitis (PBC) but are also occasionally found in other diseases. In the present study, we evaluated the incidence of and predictors for PBC development in AMA‐positive patients with other liver or non‐liver diseases at baseline. In this retrospective study, we screened patients who tested positive for AMA and/or anti‐mitochondrial M2 antibody (AMA‐M2) at Beijing Friendship Hospital, Capital Medical University, from October 2005 to January 2017. They were categorized by their diagnosis at the baseline as patients with PBC or non‐PBC cases. We followed up on the non‐PBC cases through telephone interviews and reviewing of medical records to obtain laboratory results and clinical outcomes. In total, 139 patients were AMA‐positive but did not fulfill the diagnostic criteria of PBC at baseline, including 51 patients with non‐PBC liver diseases and 88 cases with non‐liver diseases. The titers of AMA‐M2, alkaline phosphatase, gamma‐glutamyl transpeptidase, and immunoglobulin M were significantly higher in patients with PBC compared to those with non‐PBC liver diseases and non‐liver diseases. After a median follow‐up of 4.6 (interquartile range: 2.4–7.6) years, 4.3% (6 of 139) developed PBC, with an accumulative 5‐year incidence rate of 4.2%. None of the patients with non‐PBC liver diseases developed PBC, whereas the 5‐year incidence rate of PBC was 7.8% among 88 patients with non‐liver diseases. Lower alanine aminotransferase and higher immunoglobulin M were independent predictors for developing PBC. Conclusion: Our results suggest a low risk of developing PBC over time in AMA‐positive patients with other liver and non‐liver diseases.

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Antimitochondrial Antibodies: from Bench to Bedside

Cited by 42 publications

References 118 publications

A New Role of NAP1L1 in Megakaryocytes and Human Platelets

A New Role of NAP1L1 in Megakaryocytes and Human Platelets

Using two-step cluster analysis to classify inpatients with primary biliary cholangitis based on autoantibodies: A real-world retrospective study of 537 patients in China

The future risk of primary biliary cholangitis (PBC) is low among patients with incidental anti‐mitochondrial antibodies but without baseline PBC

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