Huntingtin Interacting Protein 1 (HIP1) autoantibodies as a novel potential surrogate marker for Rheumatoid Arthritis: Pilot Study

Rheumatoid Arthritis (RA), an autoimmune disease, primarily affects synovial joints but has systemic manifestations upon progression. Considering limited specific diagnostic and prognostic biomarkers, identifying the disease early and monitoring its progression is important. Previous reports have shown that Huntingtin Interacting Protein 1 (HIP1) is over-expressed in rat synoviocytes, and its autoantibodies in sera of some cancers has diagnostic relevance. Here, we explored HIP1 and its autoantibody levels along with Th1/Th2/Th17 cytokines in sera of RA patients for their potential as surrogate markers. Relative level of autoantibodies to HIP1 was detected using an in-house developed ELISA. HIP1 expression was found comparable in RA patients and controls. HIP1 autoantibodies were found significantly raised in RA patients (p=0.002) and were higher in patients with active disease, thereby correlating with disease progression (p=0.042). Elevated Th1 and IL-6 cytokines (p=0.024) were found in a subset of patients with active disease, coinciding with their pro-inflammatory profile. This is the first report demonstrating a humoral immune response against HIP1 in RA patients, correlating with an active disease status. Further studies in a larger cohort are required to validate this as a surrogate marker. Key Points HIP1 autoantibodies are significantly increased in sera of RA patients. HIP1 autoantibodies correlate with active disease in RA patients.