Disease relevance of Trim21

• Patients affected by Sjögren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52 [1].
• The pups from mice immunized with the Ro52 peptides had no symptoms of neonatal lupus apart from bradycardia [2].
• The degree of sialadenitis (focus score) appeared not to influence reactivity to the Ro52 kD protein [3].

High impact information on Trim21

• The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability [1].
• Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides [4].
• The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot [5].
• The role of polyclonal B-cell activation was examined by measuring total gamma-globulin as well as IgG reactive with other nuclear antigens including Ro60, Ro52 and La, which although not a major component of the autoantibody responses in these mice, did show small but significant increases following immunization with M. bovis [6].
• The putative leucine-zipper and zinc-finger motifs present in human Ro52 were conserved in the mouse protein [7].

Biological context of Trim21

• Ro52 may therefore rely upon an association with other molecules for any specific nuclear transport [8].
• These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development [9].
• Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice [10].

Anatomical context of Trim21

• This relative localization was supported by a preponderance of the Ro52 antigen in the cytoplasmic rather than nuclear fraction of enucleated cell lines detected by immunoblotting [8].
• Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway [1].
• Thus, we suggested that the binding of IgG to the apoptotic keratinocytes might be mediated through the interactions with the surface exposed Ro52 [11].

Analytical, diagnostic and therapeutic context of Trim21

• Immunofluorescence staining of human (HEp-2) and mouse (LTA-5) cell transfectants with affinity-purified anti-Ro52 antibodies revealed that Ro52 antigen was most abundant in the cytoplasm and present to a lesser extent in the nucleus [8].
• METHODS: DNA and nucleosome antibodies were detected by ELISA, antibodies to SmB, U1A-RNP, Ro52, Ro60 and La by a new radioligand assay, using de novo synthesized radio-labeled antigens [12].

References