Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary biliary cirrhosis and primary Sjogren's syndrome
✍ Scribed by T Dorner; E Feist; C Held; K Conrad; G R Burmester; F Hiepe
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 216 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Primary biliary cirrhosis (PBC) is an autoimmune hepatic Antibodies against the 52-kd Ro(SS-A) protein are sigdisease of hitherto unknown etiology with various extrahenificantly associated with the primary Sjo ¨gren's synpatic findings. 1 Autoantibodies against the mitochondrial indrome (pSS). A small proportion of patients suffering ner membrane antigen defined as M 2 (AMA 2) are of great from primary biliary cirrhosis (PBC) with secondary specificity for this entity. 2 The frequencies of xerostomia and Sjo ¨gren's syndrome (PBC/SS) who are serologically keratoconjunctivitis sicca in PBC patients vary between 21% characterized by antimitochondrial type 2 antibodies and 81%. [3][4][5][6][7][8][9] Previously, we investigated 40 PBC patients. also express anti-52-kd Ro(SS-A) antibodies. The pri-Seven of them contained anti-52-kd Ro(SS-A) antibodies, mary B-cell-derived antigenic responses by autoimalmost always in association with the secondary Sjo ¨gren's mune sera were analyzed in both entities using trunsyndrome (PBC/SS). 10 These antibodies were also detected in cated recombinant proteins to examine whether 23% of patients with autoimmune hepatitis. 9 different epitopes are associated with these diseases.
Several studies have determined immunogenic regions on Sera were collected from 25 patients with pSS and 9
the 52-kd Ro(SS-A) protein, [11][12][13][14][15][16][17][18] providing some variable reanti-52-kd Ro(SS-A)-positive patients suffering from sults depending on the patient populations, detection meth-PBC/SS. B-cell epitope mapping was performed using ods, different recombinants used, or synthetic peptides. Nevdifferent 52-kd Ro(SS-A) fusion proteins in enzymeertheless, most of these studies showed antigenic sites within linked immunosorbent assay (ELISA) and immunoblotthe central region of the antigen. [11][12][13][15][16][17][18] In initial studies by ting. Sera from patients with pSS showed the broadest our group, immunodominant autoepitopes within AA 153reactivity against antigenic epitopes at AA 153-245 com-245 of the antigen were determined using a limited number pared to the significantly limited reactivity against AA of various autoimmune sera. 18 In the present study we have 228-245 of sera from patients with PBC. B-cell epitopes continued these analyses using extended series of pSS and within AA 190-245 represent immunodominant epitopes PBC/SS sera to elucidate whether the immune response berecognized by pSS sera in a significantly higher degree tween pSS and PBC/SS sera are induced by different immuthan by PBC sera, which react predominantly with AA nological mechanisms.
228-245 (P õ .0001). Anti-La(SS-B) antibodies were signif-
The data obtained show that the immunodominant region icantly associated with anti-52-kd Ro(SS-A) in sera from recognized by PBC/SS sera was significantly restricted to AA patients with pSS compared with PBC patients (P õ 228-245, whereas pSS serum samples reacted to AA 153-.025). Thus, the antibody response to 52-kd Ro(SS-A) in 245 with significantly stronger antibody reactivities. These PBC appears to be induced differently than in pSS. Alresults suggest that the immune responses to 52-kd Ro(SSthough a limited immune response to 52-kd Ro(SS-A)
A) are significantly different between these entities. occurs in PBC/SS patients, a more extended epitope spreading is evident in patients with pSS. (HEPATOLOGY PATIENTS AND METHODS 1996;24:1404-1407.)
Patient Population
The diagnostic value of autoantibodies to the Ro(SS-A) Sera were obtained from 25 patients with pSS and 9 patients components is well known for the primary Sjo ¨gren's synwith PBC/SS from the university hospitals of the Charite ´Berlin. drome (pSS), systemic lupus erythematosus (SLE), subacute Epidemiological data of these groups are summarized in Table 1.
Diagnosis of pSS was established according to the European Commucutaneous lupus erythematosus, neonatal lupus erythematonity criteria. 19 The patients with PBC/SS were selected out of 52 sus, and congenital heart block. These antibodies also occur patients with PBC. Clinical data of 40 PBC patients who were inin other autoimmune diseases, although in lower frequencies.
cluded in this study have been reported previously. 10 Diagnosis of PBC was based on the presence of clinical, biochemical, serological, and hepatic histological data, which were classified in accordance with Ludwig et al. 20