SERUM ANTI-MITOCHONDRIAL ANTIBODIES IN SYSTEMIC SCLEROSIS RECOGNIZE VARIABLE PYRUVATE DEHYDROGENASE COMPLEX ANTIGENS

ANGELA CERIBELLI; NATASA ISAILOVIC; CAROLINA GORLINO; ELENA GENERALI; MARIA DE SANTIS; GIACOMO MARIA GUIDELLI; MARTA CAPRIOLI; PIERCARLO SARZI-PUTTINI; MINORU SATOH; CARLO SELMI

Madrid

Congreso; Annual European Congress of Rheumatology, EULAR 2019; 2019

European League Against Rheumatism (EULAR)

Serum anti-mitochondrial antibodies (AMA) are the hallmark of primary biliary cholangitis (PBC) and are identified also in systemic sclerosis (SSc) patients with limited variant and serum anti-centromere antibodies (ACA). Indirect immunofluorescence (IIF) shows the cytoplasmic pattern that characterizes AMA positivity, but it is usually performed when a suspect of PBC is already present. Protein-immunoprecipitation (IP) and IP-Western Blot (WB) have the advantage of 1) identify AMA in an early screening phase, before the onset of PBC and liver function abnormal- ities; 2) detect the proteins that constitute the pyruvate dehydrogenase complex (PDC) complex (the subunits E1a, E1b, E2/E3, and E3BP) which seem to be associated to different risk of PBC onset. The aim of this study was to determine the prevalence and clinical significance of the PDC complex subunits in AMA positive SSc patients with and without PBC. Sera from 279 consecutive patients with rheumatic disease (146 with SSc, 77 with undifferentiated connective tissue disease ?UCTD- , and 56 with polymyositis/dermatomyositis -PM/DM) were tested by protein-IP for the screening of serum autoantibodies. In 15/58 (26%) patients with protein-IP AMA pattern we confirm a diagnosis of PBC, and all of them had a diagnosis of SSc without additional rheumatic disease. Their expression of the PDC subunits is variable by IP-WB, but this variability is not associated with specific clinical and laboratory features. In the 42/58 (72%) cases with AMA protein-IP pattern but without clinical and histological evidence of PBC, the E2 component of the PDC was detected in all except one patient, while the expression of the other proteins of the PDC was significantly less represented, i.e. E3BP in 14/42 (33%), E1b in 13/42 (31%), E3 in 6/42 (14%), and E1a in 4/42 (10%) patients. The IIF analysis on Hep2 cells of AMA positive samples also shows different patterns of expression, which spans from cytoplasmic positive staining with a reticular pattern in AMA positive sera for all the PDC proteins recognized by AMA, to cytoplasmic speckled pattern in cases with incomplete expression of PDC antigens. So far, no specific clinical correlation was identified in these patients, as they did not have a diagnosis oPBC or other autoimmune liver disease or manifested elevated liver function tests. Conclusion: The expression of the PDC antigenic components is variable both in SSc patients with AMA positive PBC and in SSc patients AMA positive without PBC or altered liver function tests, but we could not identify a clinical significance of this variability. It may be necessary to maintain a strict follow-up of these patients and to perform longitudinal studies to determine the prognostic value of this variable expression of PDC components in the onset of PBC.