Reference

Identification of 2-nonynoic acid, a cosmetic component, as a potential trigger of primary biliary cirrhosis

All Rights Reserved. Identification of 2-nonynoic acid, a cosmetic component, as a potential trigger of primary biliary cirrhosis. Rieger, Roman; Leung, Patrick S. C.; Jeddeloh, Melissa R.; Kurth, Mark J.There are some reagents with their cas registry numbers 880-52-4 and 1846-70-4 are used in this study.; Nantz, Michael H.; Lam, Kit S.; Barsky, Daniel; Ansari, Aftab A.; Coppel, Ross L.; Mackay, Ian R.; Gershwin, M. Eric (Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA). Journal of Autoimmunity, 27(1), 7-16 (English) 2006 Elsevier B.V. CODEN: JOAUEP. ISSN: 0896-8411. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Antimitochondrial antibodies (AMA) are unique among autoimmune serol. reactants because of their extremely high assocn. with the index disease primary biliary cirrhosis (PBC). This autoantibody response is specifically directed only to the lipoyl domain of the mitochondrial 2-oxo-acid dehydrogenase complexes, which prompted us to search for environmental mimotopes in the form of xenobiotics and led to our identification of 2-octynoic acid as a high-affinity reactant for AMA. To focus on the chem. characteristics requisite for binding of AMA to the xenobiotic-modified self-peptide, quant. structure-activity relationship (QSAR) studies were performed using a panel of alkynoic compds., including examn. of the length of the carbon chain and the location of the triple bond in the identified mimotope. Analyses of octynamides that varied in the position of the triple bond demonstrated that only the 2-octynamide reacted strongly with PBC sera. Furthermore, among 2-alkynamides with varying carbon chain length, 2-octyn-, 2-nonyn- (particularly) and 2-decynamide exhibited the highest reactivity. Thus, an optimal chem. structure of the xenobiotically modified epitope recognized by AMA-pos. PBC sera is provided by 2-nonynoic acid. The Me ester of this compd. is ranked 2324th out of 12,945 compds. to which there is occupational exposure, with an 80% female prevalence due to its use in cosmetic products. Our findings illustrate an unusual polyreactivity of anti-PDC-E2 and support the idea of epitope mimicry in the genesis of this autoantibody and perhaps of PBC itself. .