AB1112 THE CORRELATION BETWEEN GLYCOSYLATION OF ANTI-DSDNA ANTIBODY AND LUPUS NEPHRITIS
Authors: H. Yang, J. Ye, Y. You, Z. Zhou, J. Wu
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is a disease characterized by a large amount of autoantigens leading to the production of autoantibodies and multiple organ involvement. Among them, anti-dsDNA antibody plays an important role in SLE. Glycosylation is a post-translational modification of protein. And the glycosylation of immunoglobulins, especially IgG, can affect their function and activity. Our previous research has shown that the glycosylation of anti-dsDNA IgG is different from that of total IgG, and it could reflect the disease activity of SLE. However, the correlation between changes in glycosylation of anti-dsDNA IgG and lupus nephritis(LN) before and after treatment is still unclear. <h3>Objectives:</h3> To observe the correlation between LN and the changes of anti-dsDNA IgG glycosylation in newly diagnosed SLE patients before and after treatment. <h3>Methods:</h3> In a cohort of 100 newly diagnosed SLE patients(Cohort 1),serum samples were collected before and after treatment. The total IgG was purified from sera and then further anti-dsDNA IgG from total IgG was purified. We used ultra high performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-ESI-QqQ MS) to detect the glycosylation level of anti-dsDNA IgG. Furthermore, statistical analysis and machine learning methods(Gradient Boost Decision Tree,GBDT) were employed to explore the glycosylation changes of anti-dsDNA IgG before and after treatment. In addition, the results were validated in another cohort of 86 newly diagnosed SLE patients(Cohort 2). <h3>Results:</h3> The sialylation of anti-dsDNA IgG2 is strongly correlated with the pathogenesis of LN and it is validated in Cohort 2. Additionally, the changes in sialylation of anti-dsDNA IgG2 are closely related to the prognosis of LN. <h3>Conclusion:</h3> The sialylation of anti-dsDNA IgG2 is closely related to the pathogenesis and prognosis of LN. <h3>REFERENCES:</h3> [1] Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349(16): 1526-33. [2] Ho A, Magder LS, Barr SG, Petri M. Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum 2001; 44(10): 2342-9. [3] Jefferis R. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 2009; 8(3): 226-34. [4] Jennewein MF, Alter G. The Immunoregulatory Roles of Antibody Glycosylation. Trends Immunol 2017; 38(5): 358-72. [5] Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol 2014; 5: 520. [6] Vuckovic F, Kristic J, Gudelj I, et al. Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome. Arthritis Rheumatol 2015; 67(11): 2978-89. [7] Sjowall C, Zapf J, von Lohneysen S, et al. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus. Lupus 2015; 24(6): 569-81. [8] Han J, Zhou Z, Zhang R, et al. Fucosylation of anti-dsDNA IgG1 correlates with disease activity of treatment-naive systemic lupus erythematosus patients. EBioMedicine 2022; 77: 103883. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>