Antibody Responses In Patients With Lyme Arthritis

Nearly 60 percent of patients who do not receive antibiotic therapy early in the illness develop intermittent or persistent arthritis, particularly affecting the knees. Moreover, a small percentage of Lyme patients who do receive antibiotic therapy suffer from persistent arthritis for months or even several years after 2-3 months of oral and intravenous antibiotic therapy. This confounding condition has been termed antibiotic-refractory, or slowly resolving, Lyme arthritis.

To gain insights into the survival of spirochetes following antibiotic therapy, researchers at the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital, Harvard Medical School, and the National Center for Infectious Diseases at the Centers for Disease Control and Prevention teamed up to study antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis. These findings indicate that joint inflammation persists in patients with antibiotic-refractory Lyme arthritis after the disease-spreading spirochetes have been killed.

To compare antibody responses and determine their effect on Lyme arthritis, the team tested at least 3 blood serum samples each from 41 patients with antibiotic-refractory arthritis, 23 patients with antibiotic-responsive arthritis, and 10 non-antibiotic-treated controls -- arthritis patients who had contracted Lyme disease during the late 1970s before the cause of the disease was known. Samples were obtained during the period of arthritis and sometimes after several months of remission for all patient groups. The patients with antibiotic-refractory and antibiotic-responsive arthritis had a similar age range, sex distribution, and duration of arthritis prior to antibiotic therapy.

All samples were tested for IgG reactivity with Borrelia burgdorferi bacteria and 4 outer surface lipoproteins of the spirochete. Among non-antibiotic-treated patients, antibody titers to Borrelia burgdorferi remained high throughout a prolonged period of persistent arthritis, 2 to 5 years. In contrast, in patients with antibiotic-responsive arthritis, the level of antibody titers to Borrelia burgdorferi and most outer-surface proteins remained steady or decreased within the first 3 months of starting antibiotic therapy.

Consistent with this finding, these patients usually experienced relief from joint swelling during a 1-month course of oral antibiotics. In patients afflicted with antibiotic-refractory arthritis, the level of antibody titers to Borrelia burgdorferi and most outer-surface antigens increased slightly during the first 1 to 3 months of treatment. These patients suffered from persistent joint swelling for a median duration of 10 months, despite 2 to 3 months of oral or intravenous antibiotics. However, by 4 to 6 months after starting antibiotic therapy, antibody titers declined to similar levels in both antibiotic-treated groups, regardless of their differences in arthritis symptoms.

"In Lyme disease, there is a great need for a test that could be used in clinical practice as a marker for spirochetal eradication," observes Dr. Allen C. Steere, the senior author of the study. Yet, as he acknowledges, ridding the body of the Borrelia burgdorferi bacteria and its surface antigens does not always bring relief from arthritis. "Increasing antibody titers in patients usually suggested the presence of live spirochetes, whereas declining titers suggested that they had been killed," he notes. "Thus, patients with Lyme arthritis who have a sustained, gradual decline in antibody reactivity probably have the nearly complete or total eradication of spirochetes from the joint as a result of antibiotic therapy, even if joint inflammation persists after the period of infection."

Journal article: "Antibody Responses to Borrelia burgdorferi in Patients With Antiobiotic-Refractory, Antibiotic-Responsive, or Non-Antibiotic-Treated Lyme Disease," Priya Kannian, Gail McHugh, Barbara J.B. Johnson, Rendi M. Bacon, Lisa J. Glickstein, and Allen C. Steere, Arthritis & Rheumatism, December 2007.