Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

Giantin is the major Golgi autoantigen in human anti-Golgi complex sera

Kazuhisa Nozawa1, Marvin J Fritzler2, Carlos A von Mühlen3 and Edward KL Chan1*

Author Affiliations

1 Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USA

2 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

3 Department of Internal Medicine, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil

For all author emails, please log on.

Arthritis Res Ther 2004, 6:R95-R102  doi:10.1186/ar1035

Published: 15 December 2003

Abstract

Anti-Golgi complex antibodies (AGAs) are primarily associated with systemic lupus erythematosus and Sjögren's syndrome. Here we report on the immunoreactivity of AGAs against five Golgi autoantigens (giantin, golgin-245, golgin-160, golgin-95/GM130, and golgin-97) and provide data from epitope mapping on the most common Golgi autoantigen, namely giantin. A total of 80 human sera containing AGAs, as defined by indirect immunofluorescence on HEp-2 cells, were analyzed by ELISA using recombinant autoantigens and immunoprecipitation. The proportion of AGA sera that reacted with the five Golgi autoantigens was correlated with the molecular mass of the Golgi antigens. Autoantibodies to giantin, the largest Golgi autoantigen, were the predominant AGAs, being found in 50% of the AGA sera. Epitope mapping of giantin was performed using six recombinant fragments spanning the entire protein. Antigiantin-positive sera with low titer autoantibodies recognized epitopes in the carboxyl-terminal fragments that are proximal to the Golgi membrane, whereas higher titer sera exhibited strong reactivity to amino-terminal and central domains that are likely to extend from the Golgi membrane into the cytoplasm. Our working hypothesis is that aberrantly expressed Golgi complex autoantigens may be released into the immune system when cells undergo lysis. By virtue of a carboxyl-terminal transmembrane domain, giantin is likely to be more stably associated with the cytoplasmic face of the Golgi complex than are other golgins, which are peripheral proteins. The stable association of giantin with the putative released Golgi complex may contribute to its preferential autoantigenicity.

Keywords:
anti-Golgi complex antibody; autoantibody; autoimmunity; cell death; epitope mapping