Serum Autoantibodies Predictive of Early Knee Osteoarthritis Incidence

Measuring autoantibodies against methionine adenosyltransferase 2 beta (MAT2β) in serum can be highly useful for the improvement of prognostic models in osteoarthritis (OA) development and for the estimation of time to OA incidence, according to study results published in Annals of the Rheumatic Diseases.

Investigators screened autoantibodies in baseline serum samples from participants without radiographic knee OA using a Nucleic-acid Programmable Protein Arrays (NAPPA) platform against 2125 human proteins in sera. A total of 4796 participants from the Osteoarthritis Initiative (OAI), a multicenter, longitudinal and observational cohort study, were followed for 96 months.

For the current study, participants from an OAI subgroup without knee OA but with risk of developing it were compared with participants from a control subgroup without OA or baseline risk factors. Researchers analyzed MAT2β reactivity and verified it using NAPPA-Enzyme Linked Immunosorbent Assay (ELISA) in 100 participants who did develop knee OA during the 96-month follow-up (incident group), 100 participants who remained radiographically healthy (nonincident group), and 127 individuals who were not a part of the previous screening. Associations were assessed through the combination of a number of robust biostatistics analyses (Receiver Operating Characteristic, logistic regression, and Kaplan-Meier curves); samples from the progression subcohort were used to replicate the proposed prognostic model.

From baseline serum samples, 6 significantly different autoantibodies were found in samples from incident participants compared with nonincident participants, and the high MAT2β-autoantibody levels (0.58±0.22 vs 0.49±0.23 arbitrary units (au), respectively; P =3.140E-04) were significantly associated with future knee OA and earlier disease development. Inclusion of MAT2β reactivity in the analyses greatly improved the classification/identification of participants who would develop knee OA during the follow-up period.

Investigators created a prognostic model for incident radiographic knee OA that synthesized the various biostatistics analyses of the following biomarkers: age, sex, body mass index (BMI), knee bending, history of injury, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores, and MAT2β reactivity. They demonstrated the use of the model in the case of a 45-year-old (0 points) woman (18 points) with a BMI of 23 kg/m² (27 points), with no knee injury history (0 points), who engaged in frequent knee bending activity (21 points), with a WOMAC pain score of 2.5 (10 points), and a MAT2β-autoantibody reactivity level in serum of 1.2 au (57.5 points), for a total of 133.5 points. This value resulted in a 55.5% probability of developing radiographic knee OA over the course of 96 months.

“The present study shows that a high antibody reactivity against MAT2β protein in serum is associated at baseline with individuals who will develop incident radiographic [knee] OA, and also with an earlier appearance of the disease. Our results suggest that the inclusion of MAT2β-[autoantibody] in a clinical prognostic model for radiographic [knee] OA could improve the identification of individuals who will develop the disease before 96 months,” the investigators concluded.

Reference

Camacho-Encina M, Balboa-Barreiro V, Rego-Perez I, et al. Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative [published online August 30, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215325