Anti-U11/U12 Antibodies as a Rare but Important Biomarker in Patients with Systemic Sclerosis: A Narrative Review

Abstract

Anti-nuclear (ANA) are present in approximately 90% of systemic sclerosis (SSc) patients and are key biomarkers in supporting the diagnosis and determining the prognosis of this disease. In addition to the classification criteria autoantibodies for SSc [i.e., anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA polymerase III], other autoantibodies have been associated with important SSc phenotypes. Among them, anti-U11/U12 ribonucleoprotein (RNP) antibodies, also known as anti-RNPC-3, were first reported in a patient with SSc, but very little is known about their association and clinical utility. The U11/U12 RNP macromolecular complex consists of several proteins involved in alternative mRNA splicing. More recent studies demonstrated associations of anti-anti-U11/U12 antibodies with SSc and severe pulmonary fibrosis as well as with moderate to severe gastrointestinal dysmotility. Lastly, anti-U11/U12 autoantibodies have been strongly associated with malignancy in SSc patients. Here, we aimed to summarize the knowledge of anti-U11/U12/RNPC-3 antibodies in SSc, including their seroclinical associations in a narrative literature review.

Protein profiling in systemic sclerosis patients with different pulmonary complications using proteomic antibody microarray

“…Previous studies have investigated serum biomarkers for SSc pulmonary complications owing to the convenience of measuring them. For SSc related ILD, it has been reported that high levels of anti-U11/U12 antibodies, human epididymis protein 4, secreted frizzled receptor protein 4, transcription factor scleraxis, endothelin-1, cold-inducible RNA-binding protein, Krebs von den Lungen-6, surfactant protein D, CA15-3, and intercellular adhesion molecule 1 were potential serum biomarkers for early detection and severity assessment of ILD [15][16][17][18][19][20][21][22]. Serum anti-U11/U12 antibodies are strongly associated with moderate-to-severe gastrointestinal dysmotility [22].…”

“…For SSc related ILD, it has been reported that high levels of anti-U11/U12 antibodies, human epididymis protein 4, secreted frizzled receptor protein 4, transcription factor scleraxis, endothelin-1, cold-inducible RNA-binding protein, Krebs von den Lungen-6, surfactant protein D, CA15-3, and intercellular adhesion molecule 1 were potential serum biomarkers for early detection and severity assessment of ILD [15][16][17][18][19][20][21][22]. Serum anti-U11/U12 antibodies are strongly associated with moderate-to-severe gastrointestinal dysmotility [22]. For SSc-related PAH, it has been reported that serum levels of anti-centromere antibody (especially the anti-p4.2 antibody subset), anti-vinculin antibody, IL-32, midkine, follistatin-like 3, osteopontin, chemerin, and speci c long noncoding RNAs (e.g.…”

Biomarkers in Systemic Sclerosis: An Overview

“…Scleroderma renal crisis (CRS) is the most frequent renal complication in SSc representing a medical emergency [19,[141][142][143][144][145][146][147][148][149][150]. The use of ACE inhibitors has reduced the occurrence of CRS.…”

“…CRS is characterized by malignant hypertension, microangiopathic haemolysis, microthrombosis, thrombocytopenia, vasospasm, and progressive renal failure which can be caused by a variety of causes, such as various drugs (e.g., corticosteroids, cyclosporine, and tacrolimus) [19,[141][142][143][144][145][146][147][148][149][150]. Pathologically, CRS is characterized by rather bland or subtle findings but may show the typical "onion bulb" findings, hyperplasia of the juxtaglomerular apparatus, membranous proliferation, renovascular endothelial damage, intimal proliferation, thrombotic angiopathy, microthrombi of fibrin, hemolysis, vasospasm, vascular occlusion, ischemia, necrosis, vascular remodeling and possibly fibrosis associated with hyperreninemia and accelerated hypertension [19,[141][142][143][144][145][146][147][148][149][150]. Anti-fibrillarin antibodies, anti-RNA polymerase III antibodies, and speckled pattern ANA have been closely associated with the development of SRD; however, anti-topoisomerase antibodies have also been associated with a high incidence of CRS in some populations [19,[141][142][143][144][145][146][147][148][149][150].…”

“…Pathologically, CRS is characterized by rather bland or subtle findings but may show the typical "onion bulb" findings, hyperplasia of the juxtaglomerular apparatus, membranous proliferation, renovascular endothelial damage, intimal proliferation, thrombotic angiopathy, microthrombi of fibrin, hemolysis, vasospasm, vascular occlusion, ischemia, necrosis, vascular remodeling and possibly fibrosis associated with hyperreninemia and accelerated hypertension [19,[141][142][143][144][145][146][147][148][149][150]. Anti-fibrillarin antibodies, anti-RNA polymerase III antibodies, and speckled pattern ANA have been closely associated with the development of SRD; however, anti-topoisomerase antibodies have also been associated with a high incidence of CRS in some populations [19,[141][142][143][144][145][146][147][148][149][150]. Antiphospholipid antibodies, especially IgG antiphospholipid antibodies, represent a significant risk factor for renal disease in SSc compared with antibody-negative patients [19,[141][142][143][144][145][146][147][148][149][150].…”