Investigation of the association of pulmonary fibrosis with
tumor-associated antigens and their autoantibodies in systemic sclerosis

Background. Systemic sclerosis (SSc) is a severe autoimmune connective tissue disorder characterized by autoimmunity, vasculopathy and
fibrosis. The disease exhibits a global distribution, with prevalence estimates ranging from 20 to 260 cases per million across different
populations, and predominantly affects women. Clinical manifestations are highly heterogeneous, displaying substantial variability among
individuals. In addition to skin involvement, internal organs are frequently affected, contributing to the disease's complexity. Despite
significant advancements in recent decades, the prognosis of SSc remains relatively poor in comparison to other rheumatic diseases, with a
10-year survival rate of only 60-70%. This highlights the critical need for a deeper understanding of the underlying pathogenesis and the
development of novel therapeutic strategies. An increased risk of malignancies, particularly breast and lung cancers, has been noted in SSc patients, especially among those with anti-RNA polymerase III antibodies, suggesting a potential association between SSc and cancer.
Moreover, elevated levels of several tumor-associated antigens (TAAs) have been observed in the sera of SSc patients, correlating with the
extent of organ involvement. Nevertheless, the precise relationship between autoantibodies targeting TAAs and the pathophysiology of SSc
remains poorly understood. Objectives. We aim to validate the association between TAAs and lung fibrosis in SSc and determine the relationship between autoantibodies against TAAs and SSc.
Work Program. For these purposes, well-characterized SSc patients have been recruited and serum levels of TAAs will be measured. The
association between TAAs and SSc, along with clinical manifestations, will then be evaluated. We will also assess whether autoantibodies
targeting TAAs are present in SSc patients. A protein microarray containing 120 TAAs (GeneCopoeia, PA003) will be employed to screen for
autoantibodies in both SSc patients and healthy controls. The detected autoantibodies' association with disease manifestations in SSc will be
further investigated. Additionally, conventional ELISA will be used to quantify the levels of autoantibodies of interest.