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Anti-Ro52 Autoantibody Is Common in Systemic Autoimmune Rheumatic Diseases and Correlating with Worse Outcome when Associated with interstitial lung disease in Systemic Sclerosis and Autoimmune Myositis

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Abstract

This review highlights the 30 plus years research progress since the discovery of autoantibody to Ro52/TRIM21 in patients with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SjS). After the initial expression cloning of the Ro52 cDNA, it has taken many years to the current understanding in the interesting biological function of Ro52 as an E3 ubiquitin ligase and its role in innate immune clearance of intracellular IgG-bound complex. Early observations show that anti-Ro52, mostly associated with anti-SS-A/Ro60 and/or anti-SS-B/La, is commonly found in SLE (40–70%), SjS (70–90%), neonatal lupus erythematosus (NLE, 75–90%), and subacute cutaneous lupus erythematosus (50–60%). Anti-Ro52 has long been postulated to play a direct pathogenic role in congenital heart block in NLE as well as in the QT interval prolongation in some adults. The widespread availability of the anti-Ro52 assay has led to the detection of anti-Ro52 in other diseases including autoimmune hepatitis (20–40%), systemic sclerosis (10–30%), and autoimmune myositis (20–40%). More than ten studies have pointed to an association of anti-Ro52 with interstitial lung disease and, more importantly, correlating with poor outcome and worse survival. Other studies are implicating an interesting role for anti-Ro52 in the diagnosis of certain cancers. Future studies are needed to examine the mechanism in the pathogenesis of anti-Ro52 and carefully documenting its causal relationships in different disease conditions.

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Abbreviations

ANA:

Antinuclear antibodies

ARS:

Aminoacyl-tRNA synthetase

AS:

Antisynthetase syndrome

CHB:

Congenital heart block

DM:

Dermatomyositis

ELISA:

Enzyme-linked immunosorbent assay

IFA:

Indirect immunofluorescence assay

IIM:

Idiopathic inflammatory myopathy

ILD:

Interstitial lung disease

IP:

Immunoprecipitation

JCA:

Juvenile chronic arthritis

Jo-1:

Histidyl-transfer RNA synthetase

LIA:

Line immunoassay

MCTD:

Mixed connective tissue disease

MDA5:

Melanoma differentiation associated gene 5

MSA:

Myositis-specific antibodies

NLE:

Neonatal lupus erythematosus

PAH:

Pulmonary arterial hypertension

PBC:

Primary biliary cholangitis

PM:

Polymyositis

RNP:

Ribonucleoprotein

SCLE:

Subacute cutaneous lupus erythematosus

SjS:

Sjögren’s syndrome

SARD:

Systemic autoimmune rheumatic diseases

SLA:

Soluble liver antigen

SLE:

Systemic lupus erythematosus

SSc:

Systemic sclerosis

TRIM21:

Tripartite-motif protein 21 or Ro52

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Acknowledgements

Apology in advance for any significant omission. John T. Williams is acknowledged for help with generating Fig. 2.

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  1. Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL, 32610-0424, USA

    Edward K. L. Chan

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Chan, E.K.L. Anti-Ro52 Autoantibody Is Common in Systemic Autoimmune Rheumatic Diseases and Correlating with Worse Outcome when Associated with interstitial lung disease in Systemic Sclerosis and Autoimmune Myositis. Clinic Rev Allerg Immunol 63, 178–193 (2022). https://doi.org/10.1007/s12016-021-08911-z

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