Pos1058 correlation between serum kl-6 and anti-modified protein antibodies (ampas) in rheumatoid arthritis-associated interstitial lung disease

Background Some studies have shown that Krebs von den Lungen-6 (KL-6) may be a valuable biomarker for diagnosis and stratifying prognosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). Citrullination and carbamylation are responsible for generating Anti-Modified Protein/Peptide Antibodies (AMPAs) and are associated with RA-ILD. Objectives To evaluate the correlation between serum KL-6 and AMPAs in patients with RA. Methods We conducted a cross-sectional study that included patients with RA (ACR/EULAR 2010 criteria) with available KL-6 and AMPAs data measured in blood serum at study enrolment. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. Serum KL-6 levels were measured by Lumipulse G KL-6 Kit (Fujirebio, Japan), using Chemiluminescent enzyme immunoassay (CLEIA). The reference value for KL-6 in healthy subjects was 118-627 U/mL. The inter-assay variation coefficient of the reagent was ≤ 4.4%. AMPAs repertoire tested included ACPA, anti-carbamylated protein antibodies (anti-CarP), and autoantibodies to malondialdehyde–acetaldehyde (anti-MAA). ACPA, anti-CarP, and anti-MAA were determined by homemade ELISA tests. Antigens, cut-off values, and isotypes tested are depicted in Figure 1. Spearman’s rank correlation coefficient was used to analyze the correlation between serological markers. Results A total of 128 patients were included (24 RA-ILD and 104 RA-non-ILD). Patient characteristics were as follows: female 73%, mean age 60.3 ± 12.4 years, mean disease duration 6.5 ± 4.7 years, RF positive 68%, anti-CCP positive 83.6%, erosive disease 54.7%, and mean DAS28 2.94. Most patients received treatment with methotrexate 84 (65.6%), glucocorticoids 72 (56.3%), and biological DMARDs 23 (18.0%). Among RA-ILD patients, the median FVC and DLco (% predicted value) were 79 (IQR 74.7–88.7) and 62.9 (IQR 53.1–70.6), respectively. Usual interstitial pneumonia (UIP) was found in 11/24 (45.8%) patients. The mean KL-6 level was 476.4 ± 400.9 U/mL. KL-6 levels were elevated in 22 patients (17.2%). Serum levels of KL-6 in the RA-ILD group were significantly higher than those in the RA-non-ILD group (756.0 ± 673.4 U/mL vs. 411.9 ± 273.0 U/mL; p<0.001). Serum KL-6 had a moderate positive correlation with HSA-MAA IgA ( r =0.56; p=0.048) in patients with non-UIP pattern ( Figure 1 ). Anti-CarP (Fib IgG: 81.8% vs. 54.7; p=0.019) and anti-MAA antibodies (HSA-MAA IgA: 36.4% vs. 10.4; p=0.018) were significantly associated with elevated KL-6 values ( Table 1 ). Conclusion Serum KL-6 is a surrogate biomarker of ILD, elevated in a subgroup of patients with RA-ILD. KL-6 elevation correlated with some AMPAs, such as anti-CarP and anti-MAA. Whether AMPAs are potential biomarkers for RA-ILD requires further analysis. Funding Hospital Clinic of Barcelona (Grant # 37 933) and the Spanish Ministry of Economy and Competitiveness (Grant # RTI2018-094120-B-I00). References [1] Qin Y, et al. Arthritis Res Ther. 2022 [2] Haro I, et al. Int J Mol Sci. 2022 Table 1. Anti-Modified Protein/Peptide Antibodies (AMPAs) distribution according to serum KL-6 status in RA patients. Biomarker All population N=128 High KL-6 n=22 Normal KL-6 n=106 P Anti-Citrullinated Protein Antibodies (ACPA ) anti-CCP3 107 (83.6) 16 (72.7) 91 (85.8) 0.130 CFFCP1 IgG 89 (69.5) 15 (68.2) 74 (69.8) 0.880 Anti-Carbamylated Protein Antibodies (anti-CarP ) Fib IgG 76 (59.4) 18 (81.8 ) 58 (54.7) 0.019 FCS IgG 69 (53.9) 12 (54.5) 57 (53.8) 0.947 FCS IgA 39 (30.5) 10 (45.5) 29 (27.4) 0.093 CFFHP 33 (25.8) 6 (27.3) 27 (25.5) 0.860 Autoantibodies to Malondialdehyde–Acetaldehyde (anti-MAA ) HSA-MAA IgG 9 (7.0) 2 (9.1) 7 (6.6) 0.830 HSA-MAA IgM 1 (0.8) 0 1 (0.9) 0.810 HSA-MAA IgA 19 (14.8) 8 (36.4 ) 11 (10.4) 0.018 HSA-MAA IgA, ng/mL 0.5 ± 0.7 0.9 ± 0.2 0.7 ± 0.07 0.004 Fib-MAA IgG 25 (19.5) 3 (13.6) 22 (20.8) 0.661 CFFCMaP IgG 26 (20.3) 5 (22.7) 21 (19.8) 0.864 Antigens and cut-off values are specified in Figure Figure 1. Heatmap of correlation between serum KL-6 and AMPAs in patients with RA. Acknowledgements We want to thank all patients who have participated in the study. Disclosure of Interests Juan C. Sarmiento-Monroy: None declared, Albert Pérez-Isidro: None declared, Raul Castellanos Moreira Employee of: Bristol Myers Squibb, Virginia Ruiz: None declared, Beatriz Frade-Sosa: None declared, Ana Azuaga: None declared, Julio Ramírez: None declared, Maria Jose Gomara: None declared, Cristina Garcia-Moreno: None declared, Isabel Haro: None declared, Anna Colmenero: None declared, Manuel Morales-Ruiz: None declared, Estíbaliz Ruiz-Ortiz: None declared, Odette Viñas: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Juan de Dios Cañete: None declared, Raimón Sanmartí: None declared, José A Gómez-Puerta: None declared.