Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to disease manifestations,damage and antiphospholipid antibodies

Abstract

Background

Attempts are ongoing to unveil unresolved queries about anti-double-stranded deoxyribonucleic acid (anti-dsDNA), their precise pathogenic effects and to what extent blocking them would be a useful therapeutic goal.

Objectives

The aim of the present study was to determine the anti-dsDNA antibodies titre in systemic lupus erythematosus (SLE) patients and investigate their relation to the disease characteristics, activity, damage and antiphospholipid autoantibodies (aPL).

Methods

Seventy female SLE patients and 35 age- and sex-matched controls were included. The anti-dsDNA level and aPL were measured. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) were assessed.

Results

The mean age of the patients was 27.5 ± 5.1 years, disease duration 7.7 ± 5.4 years, and SLEDAI and SLICC/ACR-DI scores were 6.8 ± 8.04 and 1.2 ± 1.3, respectively. Anti-dsDNA was positive in 61.4% of the patients and the titre (133.2 ± 100.5 IU/ml) was significantly higher compared to controls (22.03 ± 17.2 IU/ml) (p < 0.0001). The anti-dsDNA level was significantly increased in those with musculoskeletal manifestations (p = 0.007) and positive anti-β2 glycoprotein (anti-β2GP) (p = 0.037) and decreased in those with neuropsychiatric manifestations (p = 0.004) and those receiving cyclophosphamide (CYC) (p = 0.013). The anti-dsDNA level tended to be higher in active patients. The anti-dsDNA titre significantly correlated with the erythrocyte sedimentation rate (p = 0.001), anticardiolipin IgG and IgA antibodies (p = 0.008) and anti-β2GP IgG (p = 0.03) and IgA (p = 0.002) and inversely with the total leucocytic count (p < 0.0001) and SLICC/ACR-DI (p = 0.001).

Conclusion

Anti-dsDNA is remarkably increased in SLE patients especially those with musculoskeletal manifestations and aPL. A protective role seems likely in those with neuropsychiatric manifestations and those receiving CYC and may form a shield against disease tissue damage.

Keywords

Anti-ds DNA SLE SLEDAI SLICC/ACR-DI antiphospholipid antibodies

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References

Petri

. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2002; 16: 847–858.

La Paglia

GMC

Leone

Lepri

et al.

One year in review 2017: Systemic lupus erythematosus. Clin Exp Rheumatol 2017; 35: 551–561.

Zharkova

Celhar

Cravens

Satterthwaite

Fairhurst

Davis

. Pathways leading to an immunological disease: Systemic lupus erythematosus. Rheumatology (Oxford) 2017; 56(Suppl 1): i55–i66.

Infantino

Grossi

Benucci

Li Gobbi

Damiani

Manfredi

. The impact of biological treatments on the anti-dsDNA and anti-nucleosome tests. Lupus 2018; 27: 40–48.

Isenberg

Manson

Ehrenstein

Rahman

. Fifty years of anti-ds DNA antibodies: Are we approaching journey’s end? Rheumatology (Oxford) 2007; 46: 1052–1056.

ter Borg

Horst

Hummel

Limburg

Kallenberg

. Measurement of increases in anti‐double‐stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheumatol 1990; 33: 634–643.

Arbuckle

McClain

Rubertone

et al.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526–1533.

Dai

Zhao

Gaskin

. Anti-dsDNA antibodies are one of the many autoantibodies in systemic lupus erythematosus. F1000Res 2015; 4(F1000 Faculty Rev): 939–939.

Petri

Orbai

Alarcón

et al.

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677–2686.

10.

Villalta

Bizzaro

Bassi

et al.

Anti-dsDNA antibody isotypes in systemic lupus erythematosus: IgA in addition to IgG anti-dsDNA help to identify glomerulonephritis and active disease. PLoS One 2013; 8: e71458–e71458.

11.

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.

12.

Gladman

Ginzler

Goldsmith

et al.

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.

13.

Isenberg

. Anti-dsDNA antibodies: Still a useful criterion for patients with systemic lupus erythematosus? Lupus 2004; 13: 881–885.

14.

Schiffer

Hussain

Wang

et al.

Lowering anti-dsDNA antibodies – what’s new?

Lupus 2002; 11: 885–894.

15.

Conti

Ceccarelli

Perricone

et al.

Systemic lupus erythematosus with and without anti-dsDNA antibodies: Analysis from a large monocentric cohort. Mediators Inflamm 2015; 2015: 328078–328078.

16.

Gamal

Fawzy

Siam

. Does anti-DNA positivity increase the incidence of secondary antiphospholipid syndrome in lupus patients? Egypt Rheumatol 2013; 35: 141–144.

17.

Sarbu

Salman-Monte

Rubio Muñoz

Lisbona

Almirall Bernabé

Carbonell

. Differences between clinical and laboratory findings in patients with recent diagnosis of SLE according to the positivity of anti-dsDNA by the Crithidia luciliae method. Lupus 2015; 24: 1198–1203.

18.

Mosca

Chimenti

Pratesi

et al.

Prevalence and clinico-serological correlations of anti-alpha-enolase, anti-C1q, and anti-dsDNA antibodies in patients with systemic lupus erythematosus. J Rheumatol 2006; 33: 695–697.

19.

Witte

Hartung

Matthias

et al.

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group. Rheumatol Int 1998; 18: 63–69.

20.

Keiserman

Ronchetti

Monticielo

Keiserman

Staub

. Concomitance of IgM and IgG anti-dsDNA antibodies does not appear to associate to active lupus nephritis. Open Rheumatol J 2013; 7: 101–104.

21.

Atta

Pereira

Santiago

Sousa-Atta

MLB

. Anti-dsDNA antibodies in Brazilian patients of mainly African descent with systemic lupus erythematosus: Lack of association with lupus nephritis. Clin Rheumatol 2009; 28: 693–697.

22.

Hou

Lin

Zhang

et al.

Abnormalities of frontal-parietal resting-state functional connectivity are related to disease activity in patients with systemic lupus erythematosus. PLoS One 2013; 8: e74530–e74530.

23.

Toledano

Sarbu

Espinosa

Bargallo

Cervera

. Neuropsychiatric systemic lupus erythematosus: Magnetic resonance imaging findings and correlation with clinical and immunological features. Autoimmun Rev 2013; 12: 1166–1170.

24.

Fragoso-Loyo

Cabiedes

Orozco-Narváez

et al.

Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus. Implications for diagnosis and pathogenesis. PLoS One 2008; 3: e3347–e3347.

25.

Zeinab

Hiam

Edmond

Assem

. Selective adsorption of antiphospholipid and anti-dsDNA autoantibodies on histidine based pseudobioaffinity adsorbent from sera of patients with systemic lupus erythematosus (SLE). J Chromatogr B Analyt Technol Biomed Life Sci 2015; 975: 77–83.

26.

Manson

Isenberg

. The origin and pathogenic consequences of anti-dsDNA antibodies in systemic lupus erythematosus. Expert Rev Clin Immunol 2006; 2: 377–385.

27.

Yung

Chan

. Mechanisms of kidney injury in lupus nephritis – the role of anti-dsDNA antibodies. Front Immunol 2015; 6: 475–475.

28.

Fassbinder

Saunders

Mickholz

et al.

Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus. Arthritis Res Ther 2015; 17: 92–92.

29.

Vlachoyiannopoulos

Toya

Katsifis

Zintzaras

Tzioufas

Moutsopoulos

. Upregulation of antiphospholipid antibodies following cyclophosphamide therapy in patients with systemic lupus erythematosus. J Rheumatol 2008; 35: 1768–1775.

30.

Jónsdóttir

Gunnarsson

Risselada

Henriksson

Klareskog

van Vollenhoven

. Treatment of refractory SLE with rituximab plus cyclophosphamide: Clinical effects, serological changes, and predictors of response. Ann Rheum Dis 2008; 67: 330–334.

31.

Prasad

Ibañez

Gladman

Urowitz

. Anti-dsDNA and anti-Sm antibodies do not predict damage in systemic lupus erythematosus. Lupus 2006; 15: 285–291.

32.

Conti

Ceccarelli

Perricone

et al.

Systemic lupus erythematosus with and without anti-dsDNA antibodies: Analysis from a large monocentric cohort. Mediators Inflamm 2015; 2015: 328078–328078.

33.

Tzioufas

Terzoglou

Stavropoulos

Athanasiadou

Moutsopoulos

. Determination of anti-ds-DNA antibodies by three different methods: Comparison of sensitivity, specificity and correlation with lupus activity index (LAI). Clin Rheumatol 1990; 9: 186–192.

34.

de la Varga Martínez

Rodríguez-Bayona

Añez

et al.

Clinical relevance of circulating anti-ENA and anti-dsDNA secreting cells from SLE patients and their dependence on STAT-3 activation. Eur J Immunol 2017; 47: 1211–1219.

35.

Abdelal

Zakaria

Sharaf

Elakad

. Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients. Egypt Rheumatol 2016; 38: 295–300.

36.

Rekvig

. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: Critical remarks. Clin Exp Immunol 2015; 179: 5–10.