Refractory Lyme arthritis may be driven by 'maladaptive immune response'
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A maladaptive immune response may be prompting arthritic complications in patients with persistent and drug-refractory Lyme disease, according to a speaker at the EULAR 2021 Congress.
“Although the infection serves as the initial trigger for Lyme arthritis, the chronic inflammatory arthritis that persists after antibiotic therapy in some patients appears to a maladaptive immune response,” Klemen Strle, PhD, of the department of immunity and pathogenesis of tick-borne diseases at Massachusetts General Hospital and assistant professor at Harvard Medical School, told attendees.
This is of particular concern because, despite increased awareness of Lyme disease, incidence has been steadily on the rise in the U.S. for the past 2 decades. The challenge in understanding the pathogenesis of Lyme arthritis is rooted in the way the infection can present. “The disease is complex and it encompasses different manifestations which vary in severity and duration,” he said.
The skin may be involved, as may the heart, the neurological system and, late in the disease course, Lyme arthritis. While most patients can be cured with antibiotics early in the infection, around 10% will experience ongoing symptoms.
“Lyme arthritis is the most common late manifestation of the disease in the United States,” Strle said, noting that roughly one-third of patients who have long-term complications experience this manifestation. He added that it usually begins a few months after the tick bite.
Joint swelling may be persistent or intermittent in these patients. “Large effusions may develop, typically without systemic involvement,” Strle said.
The standard treatment regimen is 30 days of antibiotic therapy, which can yield improvements in synovitis. “These are called antibiotic-responsive Lyme arthritis patients,” Strle said.
However, a subset of patients will experience persistent synovitis for “months or years” after infection and antibiotic therapy, according to Strle. “These are called antibiotic refractory Lyme arthritis disease patients,” he said.
This subset may develop synovial hypertrophy, inflammation and vascularization similar to other chronic arthritides similar to rheumatoid arthritis. “These patients go on to therapy with DMARDs such as methotrexate or TNF inhibitors,” Strle said. He stressed that these therapies often yield success. Arthroscopic synovectomy is frequently used in patients who fail to respond to these interventions.
Regarding the pathogenesis of refractory Lyme arthritis, Strle highlighted infection with Borrelia burgdorferi RST1 (OspC type A strain), genetic implication in the HLA-DR alleles or the toll-like receptors or a maladaptive immune response marked by interferon-gamma involvement and/or a dysregulated CD4+ Teffector/Treg ratios. “The particularly inflammatory milieu in the joints leads to autoreactive T- and B-cell responses,” Strle added.
The possible meaning of all this is that Lyme arthritis is likely a “post-infectious immune process,” according to Strle. Unfortunately, he described the evidence surrounding persistent infection after the failure of antibiotic therapy as “pretty scant.”
While he noted that TH1 and TH17 response in the synovium may be implicated, those associations remain unclear. Similarly, he suggested that autoantibodies may correlate with interleukin-10. “However, it is not clear how the initial phase can shape the post-antibiotic phase of Lyme arthritis,” he said.
“The understanding of immune determinants of disease pathogenesis we think has implications for both the diagnosis and treatment of Lyme disease and its post-Lyme complications,” Strle concluded.
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Strle K. Lyme arthritis, persisting infection or auto-immune disease? Presented at EULAR 2021 Congress; June 2-6, 2021 (virtual meeting).
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