Determination of autoantibodies to annexin XI in systemic autoimmune diseases

Abstract

Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His₆-rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His₆-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3=17), and in subacute lupus erythematosus (1=6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5=137), rheumatoid arthritis (1=21), and systemic lupus erythematosus (1=58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features. A relation between antibodies to annexins and thrombosis has so far only been known for annexin V.

Keywords

annexin XI primary antiphospholipid syndrome thrombosis

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References

Moss SE . The annexins. In: Moss SE (ed). The Annexins. Portland Press:London , 1992, pp 1–9.

Towle CA , Treadwell BV. Identification of a novel mammalian annexin . J Biol Chem 1992;267: 5416–5423 .

Tokumitsu H , Mizutani A , Hidaka H . Calcyclin-binding site located on the NH2-terminal domain of rabbit CAP-SO (annexin XI):functional expression of CAP-50 in Escherichia coli . Arch Biochem Biophys 1993;303: 302–306 .

Watanabe, M , Ando, Y , Tokumitsu, H , Hidaka, H. Binding site of annexin XI on the calcyclin molecule . Biochem Biophys Res Commun 1993;196: 1376–1382 .

Mizutani A , Usuda N , Tokumitsu H et al. CAP-50, a newly identified annexin, localizes in nuclei of cultured fibroblast 3Y1 cells . J Biol Chem 1992;267: 13498–13504 .

Mizutani A , Tokumitsu H , Kobayashi R , Hidaka H . Phosphorylation of annexin XI (CAP-50) in SR-3Y1 cells . J Biol Chem 1993;268: 15517–15522 .

Mizutani A , Watanabe N , Kitao T et al. The long amino-terminal tail domain of annexin XI is necessary for its nuclear localization . Arch Biochem Biophys 1995;318: 157–165 .

Mamiya N , Iino S , Mizutani A et al. Development-related and cell-type specific nuclear localization of annexin XI:immunolocalization analysis in rat tissues . Biochem Biophys Res Commun 1994;202: 403–409 .

Misaki Y , Pruijn GJM , van der Kemp AW , van Venrooij WJ . The 56K autoantigen is identical to human annexin XI . J Biol Chem 1994;269: 4240–4246 .

10.

Towle CA , Weissbach L , Treadwell BV . Alternatively spliced annexin XI transcripts encode proteins that differ near the amino-terminus . Biochim Biophys Acta 1992;1131: 223–226 .

11.

Sudo T , Hidaka H . Regulation of calcyclin (S100A6) binding by alternative splicing in the N-terminal regulatory domain of annexin XI isoforms . J Biol Chem 1998;273: 6351–6357 .

12.

van Venrooij WJ , Wodzig KW , Habets WJ et al. Anti-56K:a novel, frequently occurring autoantibody specificity in connective tissue disease . Clin Exp Rheumatol 1989;7: 277–282 .

13.

Misaki Y , van Venrooij WI , Pruijn GJM . Prevalence and characteristics of anti-56K/annexin XI autoantibodies in systemic autoimmune diseases . J Rheumatol 1995;22: 97–102 .

14.

Andree HAM , Stuart MCA , Hermens WT et al. Clustering of lipid-bound annexin V may explain its anticoagulant effect . J Biol Chem 1992;267: 17907–17912 .

15.

Kaburaki J , Kuwana M , Yamamoto M et al. Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus . Am J Hematol 1997;54: 209–213 .

16.

Matsuda I , Saitoh N , Gohchi K et al. Anti-annexin V antibodies in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody . Am J Hematol 1994;47: 56–58 .

17.

Arnett FC , Edworthy SM , Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis . Arthritis Rheum. 1988;31: 315–324 .

18.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus (SLE) . Arthritis Rheum 1982;25: 1271–1277 .

19.

Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee . Preliminary criteria for the classification of systemic sclerosis (scleroderma) . Arthritis Rheum 1980;23: 581–590 .

20.

Bohan A , Peter JB . Polymyositis and dermatomyositis I . New Engl J Med 1975;292: 344–347 .

21.

Alarcón-Segovia D , Villarreal M . Classification and diagnostic criteria for mixed connective tissue diseases. In: Kasukawa R , Sharp GC (eds). Mixed Connective Tissue Diseases and Anti-Nuclear Antibodies. Elsevier:Amsterdam , 1987, pp 33–40.

22.

Manthorpe R , Oxhoim P , Prause JU , Schiùdt M. The Copenhagen criteria for Sjögren's syndrome . Scand J Rheumatol 1986;61 (Suppl): 19–21 .

23.

Vitali C , Bombardieri S , Moutsopoulos H et al. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community . Arthritis Rheum 1993;36: 340–347 .

24.

Harris EN . Antiphospholipid antibodies . Br J Haematol 1990;74: 1–9 .

25.

Innis MA , Gelfand DH , Sninsky JJ , White TJ. PCR Protocols, Academic Press:San Diego , 1990.

26.

Sambrook J , Fritsch EF , Maniatis T . Molecular Cloning. Cold Spring Harbor Laboratory Press:New York, USA , 1989.

27.

Laemmeli UK . Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature 1970;227: 680–685 .

28.

Thiagarajan PMD , Benedict CR . Inhibition of arterial thrombosis by recombinant annexin V in a rabbit carotid artery injury model . Circulation 1997;96: 2339–2347 .