Background/Purpose: Although osteoarthritis (OA) has not been considered as an autoimmune disorder, there are increased evidences of the role of the immune system in OA pathogenesis. Since autoantibodies (AAbs) are produced also at asymptomatic stages, they have been proposed as potential biomarkers to identify patients without clinical symptoms. A previous work from our group demonstrated the presence of AAbs in sera from OA patients. In this study, we aimed to identify an AAbs profile associated with an increased risk for the disorder, which might be useful in the very early diagnosis of knee OA.

Methods: Nucleic-Acid Programmable Protein Array (NAPPA) platform was used to screen AAbs against 2200 human proteins in 200 sera at baseline belonging to participants enrolled in the Incidence and Non-exposed subcohorts from the Osteoarthritis Initiative (OAI). Patients from the Incidence subcohort included in the screening had developed OA at 72 months of follow-up. After a panel of 6 AAbs was stablished as associated to OA risk, levels of AAbs against MAT2B were validated by ELISA-based immunoassay in 136 and 113 sera from the same Incidence and Non-exposed subcohorts, respectively. In addition, 119 sera from patients belonging to the Incidence subcohort at baseline who have not developed OA at 72 months, named as Control-Incidence subcohort, were included in this validation step. The Kruskal-Wallis test was used to define significance, and a logistic regression analysis, adjusted by age, gender and BMI, was used to analyze the contribution of these AAbs levels to our prediction model of OA risk. Appropriate receiver-operating-characteristics (ROC) curves was also calculated.

Results: In the discovery phase of the study, the NAPPA array resulted in the identification of a panel of 6 AAbs against different human proteins significantly modulated at baseline in those patients showing specific OA risk factors. The list of proteins against which altered levels of AAbs have been found is shown in Table 1, together with the statistical metrics obtained for each AAb. MAT2B was selected to enter the validation phase owing to its implication in the methylation processes. MAT2B is the regulatory subunit of the enzyme in charge of the production of the main methyl group donor, S-adenosylmethionine. An increased levels of AAbs against MAT2B were detected in the Incidence subcohort compared to the Non-exposed subcohort (mean OD= 0.628±0.22 vs 0.553±0.21; p=0.032). The regression model of the 3 clinical variables and MAT2B AAbs levels showed a predictive power up to AUC=0.809.

Conclusion: This is the first work to screen a large number of human proteins (2200) for the detection of OA-associated AAbs. A potential panel of 6 AAbs for very early diagnosis has been defined, and MAT2B levels have been validated in individual sera from the OAI cohort. These results suggest the putative utility of a serum AAbs profile to facilitate the diagnosis of OA in a stage prior to the disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/detection-of-an-autoantibody-profile-to-characterize-patients-with-early-pre-symptomatic-knee-osteoarthritis-data-from-the-osteoarthritis-initiative/