Disease relevance of TROVE2

• SS-A/Ro is a nucleocytoplasmic ribonucleoprotein (RNP) particle that is a common target of autoimmune response in Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) [1].
• Mothers of children with neonatal lupus erythematosus (NLE) and heart block, as well as patients with Sjögren's syndrome (SS) and systemic lupus erythematosus, have serum autoantibodies that recognize SS-A/Ro autoantigens including the 60-kDa ribonucleoprotein [2].
• Anti-52- and anti-60-kDa Ro/SS-A (Ro) autoantibodies are produced by most patients with subacute cutaneous lupus erythematosus and neonatal lupus erythematosus and are thought to be pathogenic in these two disorders [3].
• The presence in serum of anti-Ro/SS-A and/or anti-La/SS-B autoantibodies is a characteristic of autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus [4].
• Patients with anti-Ro/SS-A antibody were significantly associated with the presence of vasculitis, hyperglobulinemia and rheumatoid factor in primary SS (p < 0.05) [5].

Psychiatry related information on TROVE2

• In this communication, we review the induction of autoimmune diseases via Id manipulation, the Ids of some ANA-associated Abs (DNA, SS-A, SS- B, Sm Abs), the pathogenic role of Abs carrying Ids, and the clinical implications of the Id network in autoimmunity [6].

High impact information on TROVE2

• To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro [7].
• Many lupus and Sjögren's syndrome patients, as well as most neonatal lupus infants with congenital heart block or dermatitis, have antibodies to the ribonucleoprotein Ro/SSA, which is one of a group of RNA-protein autoantigens commonly found in human lupus sera [8].
• These data indicate that the Id-Rol epitope on anti-Ro/SSA is associated with the antigen binding site of these same antibodies [8].
• The rheumatic disease autoantigen, Ro/SSA, was immunogenic to a rabbit host [9].
• By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) that interacts with the carboxyl 70% of 60-kDa SS-A/Ro [2].

Chemical compound and disease context of TROVE2

• Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus [10].
• The main risk factors for adverse pregnancy course and outcome are active disease, nephritis with proteinuria, hypertension, and maternal serum antibodies to SS-A/Ro, SS-B/La, cardiolipin, beta2-glycoprotein I, and lupus anticoagulant [11].
• They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course [12].
• Decreased levels of autoantibodies against DNA, histones, cardiolipin, RNP, Sm, Ro (SS-A), and La (SS-B) were detected in the sera of patients with uveitis receiving cyclosporine A or cyclosporine A plus bromocriptine following 3 months of treatment [13].

Biological context of TROVE2

• The sequence of the cDNA shows that the 60-kD SS-A/Ro protein possesses both RNA binding protein consensus sequences and a single zinc-finger motif [1].
• The availability of the 60-kD SS-A/Ro cDNA will enable detailed analysis of the molecular structure and function of the SS-A/Ro RNP particle and its role in autoimmune pathology [1].
• Mapping of the human 60,000 M(r) Ro/SSA locus: the genes for three Ro/SSA autoantigens are located on separate chromosomes [14].
• The predominant antibody response in the NLE group was to the newly recognized 52-kD SSA/Ro peptide component [15].
• RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls [16].

Anatomical context of TROVE2

• The identity of the cDNA encoded protein as the 60-kD SS-A/Ro antigen was established by proteolytic peptide mapping of the cDNA-encoded protein and the 60-kD HeLa cell antigen [1].
• Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjogren's syndrome [17].
• By immunoblot analysis these antibodies demonstrate that 52- and 60-kDa Ro proteins are expressed in normal human skin and cultured keratinocytes [3].
• New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60 kilodaltons) and La/SSB autoantibodies in connective tissue diseases [18].
• Can B cell epitopes of 60 kDa Ro distinguish systemic lupus erythematosus from Sjögren's syndrome [19]?

Associations of TROVE2 with chemical compounds

• UVB light and 17-beta-estradiol have different effects on the mRNA expression of Ro/SSA and La/SSB autoantigens in HaCaT cells [20].
• Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted [21].
• Antibodies to SS-A/Ro and SS-B/La were assessed by enzyme-linked immunosorbent assay (ELISA) and by sodium dodecyl sulfate (SDS)-immunoblot [22].
• Prednisone and 6-azathioprine reduced the level of IgG anti-Ro/SS-A autoantibody in sera of treated SCLE patients by 50% [23].
• Tunicamycin, an inhibitor of glycosylation of proteins, reduced UVB light effect on the SS-A/Ro and SS-B/La antigen's expression [24].

Physical interactions of TROVE2

• These purified antibodies binding the 197-207 peptide from 52 kDa Ro (anti-52LZ) bound native 60 kDa Ro as well as denatured 52 kDa Ro [25].
• The SS-A/SS-B autoantigenic complex: localization and assembly [26].
• Other RNA polymerase III products such as the cellular Ro RNAs continue to be transcribed and assembled into ribonucleoprotein complexes containing the Ro (SS-A) antigens [27].

Other interactions of TROVE2

• Based on Western blot and ELISA assays, sera from 14 of 84 mothers of children with NLE recognized pp75, including 1 mother in whom anti-SS-A/Ro antibodies were not detected [2].
• These data indicate that autoantibody responses to the 60-kDa Ro Ag can preferentially target discontinuous epitopes and that the ability to recognize continuous epitopes is accompanied by the appearance of 52-kDa Ro autoantibodies [28].
• Overall agreement of positive or negative tests between the ALBIA and IB, LIA and ELISA was 75% for chromatin, 50% for SS-A, 27.5% for Sm, 25% for Rib-P, 22.5% for RNP, 20% for Scl-70, 15% for Jo-1 and 7.5% for SS-B [29].
• The mRNA levels of calreticulin increased as a function of time after UV irradiation but the mRNA levels of 52 kDa and 60 kDa Ro mRNAs were unaltered [20].
• Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen [1].

Analytical, diagnostic and therapeutic context of TROVE2

• To address the heterogeneity of Ro and the issue of discontinuous autoepitopes, we have generated 10 overlapping recombinant polypeptides of the human 60-kDa Ro protein and compared their reactivities using a soluble immunoprecipitation assay [28].
• Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31 by fluorescence in situ hybridization [30].
• The detection of anti-Ro/SS-A and anti-La/SS-B antibodies. A comparison of counterimmunoelectrophoresis with immunoblot, ELISA, and RNA-precipitation assays [4].
• CIE is considered the most reliable to detect anti-Ro/SSA antibodies in routine practice, performing better than immunoblotting (IB) and some ELISAs [31].
• Fifteen sera which did not show Ro/SS-A antibodies by immunofluorescence tested positive for Ro/SS-A by immunodiffusion, counter-immunoelectrophesis, or ELISA; of these, 14 had ANA titres > 200 [32].

References