Disclosures: Temilola Y. Abdul, MD: No financial relationships or conflicts of interest

Objective: To determine the prevalence of neutralizing antibodies (Nab) directed against adeno-associated virus (AAV) serotype 2.5 in the serum and synovial fluid of patients with osteoarthritis (OA). This vector is being injected intra-articularly in a knee osteoarthritis (OA) clinical trial (ClinicalTrials.gov Identifier: NCT02790723), and high titers of Nab might inactivate the virus.

Design: Twenty-three synovial fluid samples were aspirated from the knee joints of patients with OA and treated with hyaluronidase to reduce viscosity. For ten of these patients, peripheral blood was also drawn and serum recovered. Serum samples were serially diluted and incubated with AAV2.5 expressing green fluorescent protein (GFP). The potency of AAV2.5GFP was assessed by its ability to express GFP in a synovial cell line, HIG-82. The presence of Nab was measured by inhibition of this process. Setting : Laboratory Participants : Patients with knee OA presenting to clinic for intra-articular injection or total knee arthroplasty.

Interventions: Not applicable

Main Outcome Measures: Inhibition of the transducing ability of AAV2.5GFP. Nab titers are expressed as the amount of dilution that gave 50% inhibition.

Results: Of the 23 synovial fluid samples tested, nine had no detectable Nab, three had high titers (1: 8,192; 1: 1,024; 1:1,024) and eleven had intermediate titers ranging from 1:1 to 1: 512. Matching synovial fluid and serum samples were recovered from 10 patients. Titers of Nab in serum correlated with those in the corresponding synovial fluid. In no case was the serum titer less than the synovial fluid titer. Conclusions: High titers of Nab against AAV2.5 are uncommon in the synovial fluids of patients with OA. Those with high titers can be identified by measuring titers in the serum, and thus offered an alternative to gene therapy using this vector or treated under conditions where their viral immune response is mitigated.

Level of Evidence: Level III

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PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/prevalence-of-anti-aav2-5-antibodies-in-synovial-fluid-and-serum-of-patients-with-osteoarthritis/