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 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Delhi Rheumatology Association & Sir Ganga Ram Hospital. We would also like to thank Council of Scientific and Industrial Research (CSIR) for providing Junior Research Fellowship to Ms Surbhi. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Sir Ganga Ram Hospital (EC/07/19/1558) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors