Detection of anti-mitochondrial 2-oxoacid dehydrogenase complex subunit's antibodies for the diagnosis of Primary Biliary Cholangitis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 268; p. 108749
• Main Authors: Poyatos, Elisabet, Morandeira, Francisco, Climent, Joan, Mas, Virginia, Castellote, José, Bas, Jordi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2024
• Subjects: 2-oxo-glutarate dehydrogenase complex (OGDC-E2); Anti-mitochondrial antibodies (AMA); Branched chain 2-oxo acid dehydrogenase complex (BCOADC-E2); Diagnosis; Primary biliary cholangitis (PBC); Pyruvate dehydrogenase complex (PDC); BCOADC-E2; Primary biliary cholangitis (PBC); gammaglobulin; IgA; IIF-AMA; IgG; ALT; IgM; PDC; AUC; PBC; Anti-mitochondrial antibodies (AMA); nPDC; OGDC-E2; UNL; AMA; Diagnosis; 95% CI; PBS; Obs; AST; OR; IIF; ROC; PDC-E2; Pyruvate dehydrogenase complex (PDC); AP; Branched chain 2-oxo acid dehydrogenase complex (BCOADC-E2); Se; GGT; LKS; 2-oxo-glutarate dehydrogenase complex (OGDC-E2); E3BP; E1, E2, E3; Sp
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2021.108749

Anti-mitochondrial antibodies (AMA), directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes, are markers of Primary Biliary Cholangitis (PBC), a chronic autoimmune liver disease. However, it has not been stablished the clinical significance of subunits-specific AMA type PDC-E2 subunit of the pyruvate dehydrogenase complex-, BCOADC-E2 subunit of the branched-chain 2-oxo acid dehydrogenase complex-, OGDC-E2 subunit of the 2-oxo-glutarate dehydrogenase complex- and nPDC -native pyruvate dehydrogenase complex (M2-AMA), and not all AMA specificities are associated with PBC. The aim of the present study was to show the usefulness of the number and combination of subunits-specific AMA positive for the diagnosis of PBC. We detected AMA by indirect immunofluorescence (IIF-AMA) and M2-AMA by dot-blot. We studied the relationship of AMA with some clinical and laboratory variables in 307 patients (37% PBC) with positive dot-blot for M2-AMA. In PBC patients, we detected different E2 subunits of the 2-oxo acid dehydrogenase complexes antibodies (M2-AMA): 82.9% were specific for nPDC, 64.5% for PDC-E2, 44.4% for BCOADC-E2, and 9.6% for OGDC-E2. IIF and dot-blot tests achieved an Area Under the Receiver Operating Characteristic Curve (ROC AUC) of 0.674 (1:320 cut-off titer, Sensibility (Se) 64.7%, Specificity (Sp) 63.4%) and 0.663 (three specificities M2-AMA, Se 43%, Sp 81.2%), respectively. The detection of different E2 subunits of the 2-oxo acid dehydrogenase complexes antibodies (M2-AMA) by dot-blot showed different ROC AUC: anti-PDC-E2 showed an AUC of 0.610, a Se of 43.7%, and a Sp of 76.4%. Finally, the combined detection of nPDC/BCOADC-E2/PDC-E2 reached an AUC of 0.6095, a Se of 59.6%, and a Sp of 70.2%.The identification of two M2-AMA specificities through dot-blot increased PBC odds ratio (OR) by 2.05 (p:0.031), as compared to the identification of one specificity. Moreover, the identification of three and four specificities increased OR by 4.63 (p:0.000) and by 21.53 (p:0.006), respectively. nPDC/OGDC-E2/PDC-E2 and nPDC/OGDC-E2/BCOADC-E2/PDC-E2 combinations increased PBC OR by 10.04 (p:0.034), as compared to any other combination. 1:320 and 1:640 IIF-AMA increased PBC OR by 4.93 (p:0.009) and 7.67 (p:0.001), respectively, as compared to IIF-AMA titers equal to or less than 1:160. M2-AMA dot-blot was less sensitive but more specific than IIF-AMA, with similar predictive capacity for PBC. Increased numbers of M2-AMA specificities clearly increased the risk of PBC. Some combinations were strongly related to PBC (nPDC/BCOADC-E2/PDC-E2), but others were not (one single M2-AMA, and nPDC plus PDC-E2). M2-AMA dot-blot was less sensitive but more specific than IIF-AMA, with similar predictive capacity for PBC. Increased numbers of M2-AMA specificities clearly increased the risk of PBC, being some combinations, such as nPDC/BCOADC-E2/PDC-E2, more related to PBC than others. Finally, the determination of the number of M2-AMA specificities was more useful than the particular subunit target for PBC diagnosis. In conclusion, the study of the number of M2-AMA specificities by dot-blot should definitely be considered for PBC diagnosis.