ADAMTS-13 metalloprotease abnormalities in systemic lupus erythematosus: is there a correlation with disease status?

Abstract

To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13 profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels, activity) in distinct patient groups according to disease activity, extent of cumulative tissue damage and history of antiphospholipid syndrome or end-organ damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13 activity was measured by Fluorescence resonance energy transfer (FRET) technique. ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) >1 (p < 0.05). ADAMTS-13 metalloprotease antigen levels also exhibited a significant inverse correlation with anti-dsDNA levels (r = −0.60, p < 0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients with positive anti-dsDNA (p = 0.08). Additionally, patients with positive anti-ADAMTS-13 autoantibodies exhibited the lowest activity levels (p < 0.05). To our knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite structured indices. The results of this study suggest that in patients with active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction. Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis of thrombotic microangiopathy in lupus patients and reveal a potential prognostic marker of microthrombotic manifestations in SLE.

Keywords

ADAMTS-13 systemic lupus erythematosus disease activity cumulative tissue damage thrombosis

Get full access to this article

View all access options for this article.

References

Kwok

Cho

Kim

Park

. Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: risk factors and clinical outcome: A single centre study. Lupus 2009; 18: 16–21.

Sadler

Moake

Miyata

George

. Recent advances in thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program 2004; 407–423.

Zheng

Kaufman

Goodnough

Sadler

. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103: 4043–4049.

Tsai

H-M

. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol 2010; 91: 1–19.

Lowenstein

Morrell

Yamakuchi

. Regulation of Weibel-Palade body exocytosis. Trends Cardiovasc Med 2005; 15: 302–308.

Letchumanan

H-J

Lee

L-H

Thumboo

. A comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus. Rheumatology (Oxford) 2009; 48: 399–403.

Lansigan

Isufi

Tagoe

. Microangiopathic haemolytic anaemia resembling thrombotic thrombocytopenic purpura in systemic lupus erythematosus: The role of ADAMTS13. Rheumatology 2010; 50: 824–829.

Al-Awadhi

Jadaon

Al-Jafar

Al-Wazzan

. ADAMTS-13 antigen and activity levels in thrombocytopenic disorders including thrombotic thrombocytopenic purpura in Kuwait. Acta Haem 2011; 125: 160–166.

Lancellotti

De Filippis

Pozzi

. Formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13: A new prothrombotic mechanism in diseases associated with oxidative stress. Free Radic Biol Med 2010; 48: 446–456.

10.

Chen

Wang

. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood 2010; 115: 706–712.

11.

Thachil

. Thrombotic thrombocytopenic purpura: Is there more than ADAMTS-13? J Thromb Haemost 2007; 5: 634–635.

12.

Musial

Swadzba

Szczeklik

. Adaptive mechanisms counterbalancing enhanced thrombinogenesis in antiphospholipid syndrome. Thromb Res 1998; 90: 93–94.

13.

Yamazaki

Asakura

Jokaji

. Plasma levels of lipoprotein(a) are elevated in patients with the antiphospholipid antibody syndrome. Thromb Haemost 1994; 71: 424–427.

14.

Matsuyama

Kuwana

Matsumoto

. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haemost 2009; 102: 371–378.

15.

Tan

Cohen

Fries

. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

16.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

17.

Soejima

. ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage. Blood 2003; 102: 3232–3237.

18.

Bombardier

Gladman

Urowitz

Caron

Chang

. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

19.

Gladman

Ginzler

Goldsmith

. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 363–369.

20.

Cook

Gladman

Pericak

Urowitz

. Prediction of short term mortality in systemic lupus erythematosus with time dependent measures of disease activity. J Rheumatol 2000; 27: 1892–1895.

21.

Abrahamowicz

Fortin

du Berger

Nayak

Neville

Liang

. The relationship between disease activity and expert physician’s decision to start major treatment in active systemic lupus erythematosus: A decision aid for development of entry criteria for clinical trials. J Rheumatol 1998; 25: 277–284.

22.

Bertsias

Ioannidis

JPA

Boletis

. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67: 195–205.

23.

Matrat

Veysseyre-Balter

Trolliet

. Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: Predictive value for renal flares. Lupus 2011; 20: 28–34.

24.

Dayal

Gordon

Tucker

Isenberg

. The SLICC damage index: Past, present and future. Lupus 2002; 11: 261–265.

25.

Miyakis

Lockshin

Atsumi

. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

26.

Liu

Feys

Dong

Zhao

Ruan

. Alteration of ADAMTS13 antigen levels in patients with idiopathic thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura and systemic lupus erythematosus. Thromb Haemost 2006; 95: 749–750.

27.

Rieger

Mannucci

Kremer Hovinga

. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005; 106: 1262–1267.

28.

Mannucci

PMVM

Forza

Teresa

Scorza

. Von Willebrand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue disases (systemic lupus erythematosus and systemic sclerosis). Haematologica 2003; 88: 914–918.

29.

Austin

Starke

Lawrie

Cohen

Machin

Mackie

. The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction. Br J Haematol 2008; 141: 536–544.

30.

Cao

Niiya

Zheng

Shang

Zheng

. Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells. J Thromb Haemost 2008; 6: 1233–1235.

31.

Hunt

. Microangiopathic haemolytic anaemias in systemic lupus erythematosus. Lupus 2009; 18: 1028–1028.