Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis
Open accessAbstract
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (≥90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. Conclusions: AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC. (Hepatology 2007.)
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Patients with PBC typically have an increased incidence, in both themselves and their families, of other autoimmune diseases (over half of patients with PBC have another autoimmune condition).
“Patients with PBC typically have an increased incidence, in both themselves and their families, of other autoimmune diseases (over half of patients with PBC have another autoimmune condition), reflecting shared genetic predisposition (most notably but not exclusively celiac disease, scleroderma, thyroid disease and Sjögren’s).37–43”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [41]
The Abstract discusses genetic susceptibility to PBC and says about 50% of patients have no symptoms—not that they have another autoimmune condition. The Discussion and familial-history section address PBC risk and antimitochondrial antibodies in relatives, but do not establish increased rates of other autoimmune diseases in patients or their families. Searches for the named autoimmune diseases and the claimed proportion found no supporting passage. (LLM, conf=0.76)
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Self-citation
- Authors
- Lazaridis, K. N., Juran, B. D., Boe, G. M., Slusser, J. P., de Andrade, M., Homburger, H. A., Ghosh, K., Dickson, R. E., Lindor, K. D., & Petersen, G. M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lazaridis, Konstantinos N.
- Venue
- Hepatology
- Published
- 2007-09
- Volume
- 46
- Issue
- 3
- Pages
- 785-792
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1988785562
- Cited by
- 128
- References
- 35
- Citations by year
- 2026: 4 · 2025: 4 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 3 · 2015: 11 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- American Liver Foundation
- American Gastroenterological Association
- National Institutes of Health
- National Cancer Institute (P50CA102701)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK68290, K23DK068290)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- primary biliary cirrhosis, antimitochondrial antibodies, first-degree relatives, familial aggregation, genetic susceptibility, sex differences, cholestatic liver disease, disease susceptibility, family registers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Autoantibodies, Disease Susceptibility, Family, Female, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Mitochondria, Liver
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