Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary biliary cirrhosis and primary Sjogren's syndrome

Abstract

Antibodies against the 52‐kd Ro(SS‐A) protein are significantly associated with the primary Sjogren's syndrome (pSS). A small proportion of patients suffering from primary biliary cirrhosis (PBC) with secondary Sjogren's syndrome (PBC/SS) who are serologically characterized by antimitochondrial type 2 antibodies also express anti‐52‐kd Ro(SS‐A) antibodies. The primary B‐cell‐derived antigenic responses by autoimmune sera were analyzed in both entities using truncated recombinant proteins to examine whether different epitopes are associated with these diseases. Sera were collected from 25 patients with pSS and 9 anti‐52‐kd Ro(SS‐A)‐positive patients suffering from PBC/SS. B‐cell epitope mapping was performed using different 52‐kd Ro(SS‐A) fusion proteins in enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. Sera from patients with pSS showed the broadest reactivity against antigenic epitopes at AA 153‐245 compared to the significantly limited reactivity against AA 228‐245 of sera from patients with PBC. B‐cell epitopes within AA 190‐245 represent immunodominant epitopes recognized by pSS sera in a significantly higher degree than by PBC sera, which react predominantly with AA 228‐ 245 (P < .0001). Anti‐La(SS‐B) antibodies were significantly associated with anti‐52‐kd Ro(SS‐A) in sera from patients with pSS compared with PBC patients (P < .025). Thus, the antibody response to 52‐kd Ro(SS‐A) in PBC appears to be induced differently than in pSS. Although a limited immune response to 52‐kd Ro(SS‐A) occurs in PBC/SS patients, a more extended epitope spreading is evident in patients with pSS.

Anti‐SLA/LP alone or in combination with anti‐Ro52 and fine specificity of anti‐Ro52 antibodies in patients with autoimmune hepatitis

“…The CC domain is the most commonly targeted region of the Ro52 irrespective of the underlying disease, while SS patients seem to have specificities against several different Ro52 epitopes including the RING, B‐box and CC domains . In PBC, a small Ro52 epitope at CC domain (aa228‐245) has been identified as dominant using different fusion proteins in ELISA and immunoblotting .…”

Antibodies to SS‐A/Ro‐52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis

“…As far as anti‐SS‐A/Ro‐52kD antibodies are concerned, it has been reported that those found in PBC differ from those occurring in primary SS in two aspects: (i) recognition of distinct epitopes within the target molecule; (ii) rate of association with anti‐SS‐B/La antibodies, much lower in PBC 20 . In the present study, anti‐SS‐A/Ro‐52kD and anti‐SS‐B/La were simultaneously detected in PBC at a significantly lower frequency than SLE.…”

Significance of Autoantibodies in Neonatal Lupus Erythematosus

“…Additional studies provided evidence that this mRNA is expressed in fetal but not adult hearts. On the other hand, a variety of studies have shown that the leucine zipper represents the major autoantigenic epitope of this protein [19][20][21][22][23][24][25][26]. Therefore, it raises the question to which degree alternative splicing products play a significant immunopathogenic role.…”