Novel biomarker for pulmonary vascular disease in systemic sclerosis patients

Favoino, Elvira; Catacchio, Giacomo; Mininni, Alessandra; Ruscitti, Piero; Riccieri, Valeria; Liakouli, Vasiliki; Corrado, Addolorata; Navarini, Luca; Ciccia, Francesco; Cipriani, Paola; Cantatore, Francesco Paolo; Valesini, Guido; Giacomelli, Roberto; Perosa, Federico

doi:10.55563/clinexprheumatol/0exnav

Cited by 2 publications

(1 citation statement)

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“…Recently, a multicentric study group identified a subset of ACA-positive patients whose anti-centromere protein A (anti-CENP-A) autoantibodies were specific for the aminoterminal epitope of CENP-A (amino acids 1–7); these specific anti-CENP-A antibodies were called anti-p4.2 antibodies, since they react with peptide 4.2 (p4.2), a peptide isolated in a phage peptide library. Anti-p4.2 antibodies were found to be associated with a diffusing capacity of the lungs for carbon monoxide (DLCO) < 70%, even in the absence of pulmonary fibrosis, suggesting a role for these autoantibodies in predicting the development of PAH vasculopathy in ACA-positive patients [ 94 ]. Other SSc-specific autoantibodies (i.e., anti-topoisomerase I and anti-RNA polymerase III) have not shown an association with PAH [ 92 ].…”

Section: Autoimmunitymentioning

confidence: 99%

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Moccaldi

Michieli

Binda

et al. 2023

IJMS

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Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies—except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended—CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease.

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Section: Autoimmunitymentioning

confidence: 99%

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Moccaldi

Michieli

Binda

et al. 2023

IJMS

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Systemic sclerosis and primary biliary cholangitis share an antibody population with identical specificity

Favoino

Grapsi

Barbuti

et al. 2023

Clinical and Experimental Immunology

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Anti-centromere (ACA) and antimitochondrial antibodies (AMA) are specific for limited-cutaneous systemic sclerosis (lcSSc) and primary biliary cholangitis (PBC), respectively, and can coexist in up to 25% and 30% of SSc and PBC patients. Here, we evaluated whether anti-centromeric protein A (CENP-A) antibodies cross-react with mitochondrial antigens. To this end, sera from two lcSSc patients (pt1 and pt4), one of them (pt4) also affected by PBC, were used as the source of ACA, previously shown to recognize different groups of amino acids (motifs) in the CENP-A region spanning amino acids 1 to 17 (Ap1-17). Pt1 and pt4 Ap1-17-specific IgG were purified by affinity-chromatography on insolubilized Ap1-17-peptide column and tested by western blotting with nuclear and cytoplasmic protein extract from HeLa cells. Immunoreactive proteins were identified by mass spectrometry and validated by immunodot. The results showed that affinity-purified SSc/PBC pt4 anti-Ap1-17 and not SSc pt1 anti-Ap1-17 Ab, specifically cross-reacted with the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen in PBC. Sequence homology analysis indicated that the motif A-x-x-P-x-A-P recognized by pt4 anti-Ap1-17 IgG and shared by CENP-A and PDC-E2, is also expressed by some members of the Human Herpesvirus family, suggesting that they may trigger the production of these cross-reacting antibodies.

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Novel biomarker for pulmonary vascular disease in systemic sclerosis patients

Cited by 2 publications

References 0 publications

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Systemic sclerosis and primary biliary cholangitis share an antibody population with identical specificity

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