A Unique Gene Signature Could Predict Poor TKA Outcomes

A unique gene signature can help predict which patients develop stiffness after knee replacement surgery, according to Hospital for Special Surgery (HSS) researchers.

Although total knee arthroplasty is a safe and effective procedure, almost 20% of TKA patients report some sort of dissatisfaction with the results. One of the possible reasons is debilitating stiffness and pain that can lead to the need for revision surgery, the researchers say.

“In some cases we can identify potential reasons for the development of stiffness, but a subset of patients develop stiffness and pain for reasons that we can’t identify,” said Miguel Otero, assistant scientist in the Orthopedic Soft Tissue Research Program and co-director of the Derfner Foundation Precision Medicine Laboratory at HSS.

This subset of patients has been diagnosed with arthrofibrosis, a condition where scar-like tissue restricts movement and causes pain in the knee.

In the study, “RNAseq Analyses of Neo-Synovial Tissues Retrieved at the Time of Revision Surgery from Patients with Stiff Knees Uncovered Arthrofibrosis-specific gene signatures,” Otero and his team were able to identify a unique gene signature that can help predict arthrofibrosis.

They broke 80 HSS patients who underwent revision knee surgery after total knee arthroscopy into three groups. Group 1 were patients who need revision surgery because of known complications that cause stiffness. Group 2 were those who had arthrofibrosis. Group 3 served as a control group. They were having revision surgery for reasons other than stiffness like instability or aseptic loosening.

By analyzing tissue samples from the joint, Otero and his team found 1,509 differentially expressed genes in the arthrofibrosis group (Group 2) compared to the Group 3. Only 435 different genes were identified in Group 1 in comparison to Group 3.

They hope to narrow the potential pool of genes down to create a more precise genetic signature for arthrofibrosis.

“Think about surgery as a massive injury. The body needs to heal the damage, and scars are often a consequences of that healing process,” Otero said. “The excessive scarring and fibrosis that we see in patients with arthrofibrosis is an overreaction to that injury, but we don’t yet know why they are overreacting or why their reaction is different from other patients who also developed stiffness after TKA.”

He added, “We want to identify cellular and molecular signatures with therapeutic and prognostic value, so that we can develop preventative therapies targeting specific genes or pathways, and also identify patients who are at risk of developing arthrofibrosis following TKA,” he said.

The findings were presented during the American Academy of Orthopedic Surgeons 2020 Virtual Education Experience.