Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects.

Moutsopoulos, H M; Skopouli, Fotini N.; Sarras, A K; Tsampoulas, C.; Mavridis, Anestis; Constantopoulos, S.H.; Maddison, Peter J.

doi:10.1136/ard.44.4.215

Cited by 49 publications

(13 citation statements)

References 21 publications

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“…TRIM21 is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and Sjorgen's syndrome (7)(8)(9). Anti-TRIM21 autoantibodies are diagnostic both of disease (10) and disease progression (11), and a pathologic role for TRIM21:autoantibody immune complex has been shown (12).…”

mentioning

confidence: 99%

Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function

James

Keeble

Khan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

319

382

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The human tripartite motif (TRIM) family comprises 70 members, including HIV restriction factor TRIM5␣ and disease-associated proteins TRIM20 (pyrin) and TRIM21. TRIM proteins have conserved domain architecture but diverse cellular roles. Here, we describe how the C-terminal PRYSPRY domain mediates diverse TRIM functions. The crystal structure of TRIM21 PRYSPRY in complex with its target IgG Fc reveals a canonical binding interface comprised of two discrete pockets formed by antibody-like variable loops. Alanine scanning of this interface has identified the hot-spot residues that control TRIM21 binding to Fc; the same hot-spots control HIV/murine leukemia virus restriction by TRIM5␣ and mediate severe familial Mediterranean fever in TRIM20/pyrin. Characterization of the IgG binding site for TRIM21 PRYSPRY reveals TRIM21 as a superantigen analogous to bacterial protein A and suggests that an antibody bipolar bridging mechanism may contribute to the pathogenic accumulation of anti-TRIM21 autoantibody immune complex in autoimmune disease.autoimmunity ͉ familial Mediterranean fever ͉ HIV ͉ TRIM21 ͉ TRIM5␣

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mentioning

confidence: 99%

Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function

James

Keeble

Khan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

319

382

View full text Add to dashboard Cite

show abstract

“…TRIM21 (Ro52) is a major autoantigen in diseases including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome (11)(12)(13). Autoantibodies against TRIM21 are known to form pathogenic immune complexes and are used to diagnose disease and monitor disease progression (14)(15)(16).…”

mentioning

confidence: 99%

TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved

Keeble

Khan

Förster

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

173

180

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The newly identified tripartite motif (TRIM) family of proteins mediate innate immunity and other critical cellular functions. Here we show that TRIM21, which mediates the autoimmune diseases rheumatoid arthritis, systemic lupus erythematosus, and Sjö gren's syndrome, is a previously undescribed IgG receptor with a binding mechanism unlike known mammalian Fc␥ receptors. TRIM21 simultaneously targets conserved hot-spot residues on both Ig domains of the Fc fragment using a PRYSPRY domain with a preformed multisite interface. The binding sites on both TRIM21 and Fc are highly conserved to the extent that the proteins are functionally interchangeable through murine, canine, primate, and human species. Pre-steady-state analysis exposes mechanistic conservation at the level of individual residues, which make the same energetic and kinetic contributions to binding despite varying in sequence. Together, our results reveal that TRIM21 is a previously undescribed type of IgG receptor based on a non-Ig scaffold whose interaction at the fundamental level-structural, thermodynamic, and kinetic-is evolutionarily conserved.PRYSPRY ͉ systemic lupus erythematosus ͉ TRIM5␣ ͉ Ro52

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“…TRIM21 (Ro52) was first identified as a major autoantigen in autoimmune diseases including rheumatoid arthritis, SLE and Sjorgen's syndrome [60][61][62].…”

Section: Alternative Trim21 Functions -Proinflammatory Signalling Andmentioning

confidence: 99%

Intracellular antibody‐mediated immunity and the role of TRIM21

et al. 2011

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Protection against bacterial and viral pathogens by antibodies has always been thought to end at the cell surface. Once inside the cell, a pathogen was understood to be safe from humoral immunity. However, it has now been found that antibodies can routinely enter cells attached to viral particles and mediate an intracellular immune response. Antibody-coated virions are detected inside the cell by means of an intracellular antibody receptor, TRIM21, which directs their degradation by recruitment of the ubiquitin-proteasome system. In this article we assess how this discovery alters our view of the way in which antibodies neutralise viral infection. We also consider the antiviral function of TRIM21 in the context of its other reported roles in immune signalling and autoimmunity. Finally, we discuss the conceptual implications of intracellular antibody immunity and how it alters our view of the discrete separation of extracellular and intracellular environments.

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Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects.

Cited by 49 publications

References 21 publications

Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function

Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function

TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved

Intracellular antibody‐mediated immunity and the role of TRIM21

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