Autoantibodies from primary biliary cirrhosis patients with anti-p95c antibodies bind to recombinant p97/VCP and inhibit in vitro nuclear envelope assembly

Author:

MIYACHI K1,HIRANO Y2,HORIGOME T2,MIMORI T3,MIYAKAWA H4,ONOZUKA Y5,SHIBATA M6,HIRAKATA M7,SUWA A7,HOSAKA H8,MATSUSHIMA S9,KOMATSU T9,MATSUSHIMA H1,HANKINS R W1,FRITZLER M J10

Affiliation:

1. Health Sciences Research Institute

2. Niigata University, Faculty of Science

3. Kyoto University

4. Teikyo Misonokuchi Hospital

5. Social Insurance Central Hospital

6. East Kanto NTT Hospital

7. Keio University, School of Medicine

8. Yokohama Nanbu Hospital

9. Yokohama Medical Center, National Hospital, Japan

10. University of Calgary, Faculty of Medicine, Calgary, Canada

Abstract

SUMMARY We have reported previously that p95c, a novel 95-kDa cytosolic protein, was the target of autoantibodies in sera of patients with autoimmune hepatic diseases. We studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein from [35S]-methionine-labelled HeLa lysates and had a specific precipitin band in immunodiffusion. Thirteen sera were available to test the ability of p95c antibodies to inhibit nuclear envelope assembly in an in vitro assay in which confocal fluorescence microscopy was also used to identify the stages at which nuclear assembly was inhibited. The percentage inhibition of nuclear envelope assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and the swelling of nucleus was inhibited at several stages. The percentage inhibition of nuclear assembly was correlated with the titre of anti-p95c as determined by immunodiffusion. To confirm the identity of this autoantigen, we used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a radiolabelled recombinant protein that was then used in an immunoprecipitation (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97 have similar molecular masses and cell localization, and because the majority of sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly, this is compelling evidence that p95c and p97/VCP are identical.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference38 articles.

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2. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology;Tan;Adv Immunol,1989

3. Autoantibodies in the diagnosis of systemic rheumatic disease;Von Muhlen;Semin Arthritis Rheum,1995

4. Autoimmunity and primary biliary cirrhosis;Mackay;Bailliéres Clin Gastroenterol,2000

5. Anti-mitochondrial antibodies;Fritzler;Clin Appl Immunol Rev,2002

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