SAT0037 HIGH AGREEMENT BETWEEN ANTIBODIES AGAINST MALONDIALDEHYDE PROTEIN ADDUCTS AND ANTIBODIES AGAINST MALONDIALDEHYDE-ACETALDEHYDE ADDUCTS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Gonzalez, L. Rodríguez-Martínez, C. Regueiro, E. Perez-Pampín, A. Mera Varela
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) presents high levels of oxidative stress and reactive species such as malondialdehyde, which modifies proteins forming malondialdehyde adducts (MaP) and, in the presence of acetaldehyde generates adducts called malondialdehyde-acetaldehyde (MaaP). Recently, the presence of malondialdehyde modified proteins in the synovium and antibodies against these adducts (AMaPA) in the serum of patients with RA has been described (1). Previously, a high frequency of antibodies against MaaP (AMaaPA) had been reported in patients with RA (2). Objectives: We aimed to confirm the presence of AMaPA in patients with RA and define its relationship with AMaaPA. Methods: The sera of 204 healthy controls and 205 patients with established RA that met the 1987 ACR classification criteria and selected to represent the different AMaaPA status were studied. All had information on their status for FR, anti-CCP and AMaaPA antibodies (IgG, IgM and IgA). The AMaPA were determined by indirect ELISA using malondialdehyde-modified serum bovine albumin as antigen and specific secondary antibodies against the IgG and IgM isotypes following the same protocol of the previous study (1). The results were analyzed with the gamma coefficient (γ) for concordance in status and with the Spearman coefficient (ρ) for correlation of titres. The study was approved by the CEIC of Galicia. Results: The AMaPA showed higher titres in the patients with RA than in the controls, the positive frequencies being: 17.1% for IgG AMaPA and 25.4% for IgM AMaPA. An important fraction of the patients with RA showed the same status with the two AMaPA isotypes, as reflected in the significant concordance between them (γ = 0.74, Table 1). When comparing the AMaPA and AMaaPA status in patients with RA, a remarkable concordance was observed among the antibodies of the same isotype, especially between the IgM AMaPA and IgM AMaaPA: γ = 0.83 (Table 1). There were fewer patients with the same status when different antibody isotypes were compared, although some of these comparisons reached statistically significant concordance. However, the titres were not significantly correlated in any of the comparisons, even in those that showed the greatest agreement in status (Table 1). Table 1. Relationship of antibodies against malondialdehyde adducts (AMaPA) with other autoantibodies in patients with RA. AMaPA 2nd antibody ϒ P ρ P IgG IgM AMaPA 0.74 1.5E-14 0.23 0.3 IgM IgM AMaaPA 0.83 3.4E-25 0.26 0.1 IgG IgG AMaaPA 0.65 2.4E-08 0.11 0.7 IgM IgA AMaaPA 0.42 0.0017 0.26 0.4 IgG IgM AMaaPA 0.39 0.00096 0.08 0.8 IgG IgA AMaaPA 0.21 0.2 -0.09 0.9 IgM IgG AMaaPA 0.16 0.3 0.13 0.7 IgM RF 0.48 0.000011 na na IgM Anti-CCP 0.39 0.00076 -0.34 0.031 IgG Anti-CCP 0.05 0.7 -0.18 0.4 IgG RF 0.02 0.9 na na In relation to the typical RA autoantibodies, significant concordances were observed between the IgM AMaPA and RF or anti-CCP, although they were lower than those observed with the AMaaPA. In contrast, the IgG AMaPA showed no significant agreement with RF or anti-CCP antibodies. These low levels of concordance were reflected in the lack of significant difference in the prevalence of AMaPA between seronegative and seropositive patients (24.1% vs. 35.4%, P = 0.1). Conclusion: The presence of AMaPA in patients with RA has been confirmed, and a high concordance between the AMaPA and AMaaPA status has been observed, especially between those with an IgM isotype. However, the lack of correlation in the titres indicates that these two types of autoantibodies are independent. The potential utility as biomarkers of the AMaPA should be similar to that of the AMaaPA. References: [1] Grönwall C, et al. J Autoimmun. 2017, 84:29-45 [2] Thiele GM, et al. Arthritis Rheumatol. 2015, 67:645-55 Acknowledgments: Funded by the Carlos III Health Institute projects PI17/01606 and RD16/ 0012/0014 that are partially co-funded by FEDER Disclosure of Interests: None declared