Journal of immunology research · 2026
Novel Biomarker for Antimitochondrial Antibodies in Systemic Sclerosis Patients.
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Favoino Elvira, Santis Silvia De, Liakouli Vasiliki, Barbuti Giovanna, Piccolo Sabina, Corrado Ada, Vomero Marta, Navarini Luca, Prete Marcella, Leone Patrizia, Racanelli Vito, Grembiale Rosa Daniela, Ruscitti Piero, Cantatore Francesco Paolo, Ciccia Francesco, Giacomelli Roberto, Perosa Federico
Аннотация
OBJECTIVE: We previously identified, using a synthetic peptide, namely peptide 4.33 (p4.33), a subgroup of anti-CENP-A antibodies (Abs) recognizing an epitope shared between the CENP-A region spanning amino acids 1-17 (Ap1-17) and the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial target autoantigen in primary biliary cholangitis (PBC). Here, we evaluated whether anti-p4.33 Ab positivity may be associates with a higher prevalence of antimitochondrial Ab (AMA) in systemic sclerosis (SSc) patients.
METHODS: Serum samples from 145 anti-CENPpos SSc patients were tested for anti-CENP-A, -Ap1-17, and -p4.33 Abs by ELISA. Subsequently, 32 anti-Ap1-17pos/p4.33pos and 32 anti-Ap1-17pos/p4.33neg were randomly selected and tested for AMA by immunoblotting.
RESULTS: Of 145 anti-CENPpos patients, 128 (88.2%) were anti-CENP-Apos patients, of which 103 (80.5%) were positive for anti-Ap1-17 Abs and 66 (51.6%) were positive for anti-p4.33 Abs. Of 32 selected anti-Ap1-17pos/p4.33pos patients, 15 (46.9%) were also positive for AMA targeting PDC-E2 and/or the branched chain 2-oxo acid dehydrogenase complex (BCOADC-E2). In the Ap1-17pos/p4.33neg group, AMA were detected in only two patients (6.25%). AMA positivity was statistically different between groups. Anti-p4.33 Ab levels were directly associated more than anti-Ap1-17 Ab levels with AMA levels. Sequence homology analyses demonstrated that anti-p4.33 Abs recognize an epitope (kPsaP) strongly overlapping with those of Ap1-17, PDC-E2, and BCOADC-E2, also expressed by viral and bacterial proteins.
CONCLUSIONS: Anti-p4.33 Abs may be a useful biomarker to define a subset of SSc patients with a higher prevalence of AMA. Our findings also support the hypothesis that pathogens can trigger autoimmunity.
METHODS: Serum samples from 145 anti-CENPpos SSc patients were tested for anti-CENP-A, -Ap1-17, and -p4.33 Abs by ELISA. Subsequently, 32 anti-Ap1-17pos/p4.33pos and 32 anti-Ap1-17pos/p4.33neg were randomly selected and tested for AMA by immunoblotting.
RESULTS: Of 145 anti-CENPpos patients, 128 (88.2%) were anti-CENP-Apos patients, of which 103 (80.5%) were positive for anti-Ap1-17 Abs and 66 (51.6%) were positive for anti-p4.33 Abs. Of 32 selected anti-Ap1-17pos/p4.33pos patients, 15 (46.9%) were also positive for AMA targeting PDC-E2 and/or the branched chain 2-oxo acid dehydrogenase complex (BCOADC-E2). In the Ap1-17pos/p4.33neg group, AMA were detected in only two patients (6.25%). AMA positivity was statistically different between groups. Anti-p4.33 Ab levels were directly associated more than anti-Ap1-17 Ab levels with AMA levels. Sequence homology analyses demonstrated that anti-p4.33 Abs recognize an epitope (kPsaP) strongly overlapping with those of Ap1-17, PDC-E2, and BCOADC-E2, also expressed by viral and bacterial proteins.
CONCLUSIONS: Anti-p4.33 Abs may be a useful biomarker to define a subset of SSc patients with a higher prevalence of AMA. Our findings also support the hypothesis that pathogens can trigger autoimmunity.