Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with systemic lupus erythematosus: two cases without features of scleroderma

Abstract

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)–SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud’s phenomenon, vs. 92% with scleroderma in the latter (p < 0.05). Although anti-RNAP III is highly specific for SSc, cases with coexisting anti-U1RNP are not so uncommon among anti-RNAP III positives (8%, 3/35) and may be SLE without features of SSc.

SNRPA enhances tumour cell growth in gastric cancer through modulating NGF expression

“…Previous studies have reported that the U1 snRNP complex is involved in a lot of essential activities in eukaryotic cells, such as pre‐mRNA splicing and apoptosis . Among its components, in addition to their splicing roles, U1 snRNA molecule is a major target of autoimmunity in SLE‐overlap syndromes, U1‐70K was shown to be highly associated with apoptosis . However, the roles of U1 snRNP complex and its components in tumourigenesis remain unclear.…”

Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes

“…In one small case series, 2 patients had SLE, and only 1 had SSc overlap. Unlike this study, none of our patients had overlap features, and the majority of patients had dcSSc 22 , however we only looked at a cohort of patients with established SSc.…”

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis

“…The U1 snRNP consists of U1 snRNP molecules, seven common core Sm proteins, and three specific U1 proteins [U1A (SNRPA), U1C, and U1-70 (SNRNP70)]. The U1 snRNP molecule is the main target of autoimmunity in SLE-overlap syndrome . SNRNP70 is the primary target antigen for anti-U1 snRNP autoantibodies and has been reported to be highly correlated with apoptosis .…”

“…The U1 snRNP molecule is the main target of autoimmunity in SLE-overlap syndrome. 25 SNRNP70 is the primary target antigen for anti-U1 snRNP autoantibodies and has been reported to be highly correlated with apoptosis. 26 SNRPA is a 282 amino acid protein containing 2 RNA-binding domains, consisting of four antiparallel β chains and two α helices; 27 its binding to U1 snRNA requires an N -terminal RNA-binding domain and several flanking amino acids.…”