Novel Biomarker for Antimitochondrial Antibodies in Systemic Sclerosis Patients

Objective:Wepreviouslyidentified,usingasyntheticpeptide,namelypeptide4.33(p4.33),asubgroupofanti-CENP-Aanti bodies (Abs) recognizinganepitope sharedbetween theCENP-Aregionspanningaminoacids 1-17 (Ap1-17) and theE2 componentof themitochondrialpyruvatedehydrogenasecomplex(PDC-E2), themajormitochondrial targetautoantigenin primarybiliarycholangitis(PBC).Here,weevaluatedwhetheranti-p4.33Abpositivitymaybeassociateswithahigherprevalence ofantimitochondrialAb(AMA)insystemicsclerosis(SSc)patients. Methods: Serumsamples from145anti-CENPpos SScpatientsweretestedforanti-CENP-A,-Ap1-17, and-p4.33AbsbyELISA. Subsequently,32anti-Ap1-17pos/p4.33posand32anti-Ap1-17pos/p4.33negwererandomlyselectedandtestedforAMAbyimmunoblotting. Results:Of145anti-CENPpospatients,128(88.2%)wereanti-CENP-Apospatients,ofwhich103(80.5%)werepositiveforanti Ap1-17Absand66(51.6%)werepositiveforanti-p4.33Abs.Of32selectedanti-Ap1-17pos/p4.33pospatients,15(46.9%)werealso positiveforAMAtargetingPDC-E2and/orthebranchedchain2-oxoaciddehydrogenasecomplex(BCOADC-E2). IntheAp1 17pos/p4.33neggroup,AMAweredetectedinonlytwopatients(6.25%).AMApositivitywasstatisticallydifferentbetweengroups. Anti-p4.33Ablevelsweredirectlyassociatedmorethananti-Ap1-17AblevelswithAMAlevels.Sequencehomologyanalyses demonstrated that anti-p4.33Abs recognize anepitope (kPsaP) stronglyoverlappingwith those ofAp1-17, PDC-E2, and BCOADC-E2,alsoexpressedbyviralandbacterialproteins. Conclusions:Anti-p4.33AbsmaybeausefulbiomarkertodefineasubsetofSScpatientswithahigherprevalenceofAMA.Our findingsalsosupportthehypothesisthatpathogenscantriggerautoimmunity