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Treatment-resistant Lyme arthritis may be autoimmune disease
SCIENCE AND MEDICINE
NEWS
Lyme disease vaccines are safe and effective accines against Borrelia burgdorferi have been found effective in preventing Lyme disease in two placebocontrolled trials involving more than 21 000 people from areas of the USA where Lyme disease is endemic. Lyme disease, spread by ticks, is the commonest vectorborne disease in the USA, with about 10 000 new cases being reported to the Centers for Disease Control and Prevention (Atlanta, GA) each year. The vaccines tested consist of recombinant B burgdorferi outer-surface lipoprotein A (OspA). In both trials, two doses of vaccine were given a month apart, with a booster dose at 12 months. In one trial, headed by Leonard Sigal (University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, NJ, USA), vaccine efficacy—defined as no signs or symptoms of Lyme disease and no IgG or IgM antibodies to B burgdorferi detected on western blotting—was 68% in the first year of the study, after two injections, and 92% in the second year, after the booster dose. In the other trial, led by Allen Steere (Tufts University School of Medicine, Boston, MA, USA), the efficacy of vaccine plus adjuvant—defined as no signs or symptoms of Lyme disease—
V
was 49% in the first year and 76% in the second year. Both vaccines were well tolerated, the only ill-effects being mild or moderate local and systemic reactions lasting a few days after vaccination (N Engl J Med 1998; 339: 209–15, 216–22). Arthritis and neuroborreliosis, which can be prevented with antibiotics, can develop in symptomfree infected people. Data on IgG seroconversions from Steere et al show that their vaccine was 83% effective in preventing symptomless Lyme disease in the first year and 100% effective in the second year. Sigal et al suggest that concerns about the efficacy of a vaccine that contains only a single OspA protein may be unjustified. Their vaccine “prevented Lyme disease at locations in five different states in the United States, suggesting that it provides coverage against a wide range of strains”. However, they add, no inference can be drawn about the ability of this vaccine to protect against the
European species B garinii and B afzelii. In an editorial, Roy Steigbigel and Jorge Benach (State University of New York at Stony Brook, NY, USA) say “an effective, safe, and affordable vaccine for people who live in areas where Lyme disease is endemic would be welcome” because measures to prevent exposure to ticks, such as use of insect repellents and tucking one’s trousers into one’s socks before venturing into areas where ticks are common, are “bothersome and of unknown effectiveness”. They note that the need for and frequency of booster immunisation must be investigated, since the duration of protective immunity is unknown and high antibody titres will be required to eliminate the spirochaete. “Now that the B burgdorferi genome has been sequenced, it is likely that even more effective vaccines will become available.” Dorothy Bonn
Treatment-resistant Lyme arthritis may be autoimmune disease
A
ntibiotic treatment of Lyme disease is usually effective. But a small proportion of patients develop arthritis that persists for months or years despite eradication of the causative agent, Borrelia burgdorferi. Now, evidence suggests that this treatment-resistant Lyme arthritis is an autoimmune disease, a finding that could have implications for vaccine safety. Patients with treatment-resistant Lyme arthritis have an increased frequency of the HLA allele DRB1*0401, which is also associated with rheumatoid arthritis. So, Dawn Gross (Tufts University, Boston, MA, USA) and US col-
THE LANCET • Vol 352 • August 1, 1998
leagues hypothesised that this allele might bind part of the B burgdorferi outer-surface lipoprotein A (OspA). By in-vitro and animal studies, the team identifed the specific immunodominant OspA epitope. A gene-bank search then revealed a human protein—leukocyte-function-associated antigen 1 (LFA-1)—which has sequence homology to the OspA epitope and so could act as an autoantigen. T cells from patients with treatment-resistant Lyme arthritis, but not those from patients with other chronic arthritides, reacted to whole OspA, the immunodominant OspA epitope, and LFA-1. The
authors propose that an immune reaction to B burgdorferi may upregulate LFA-1, and start a “vicious cycle”, in which T cells continue to react to LFA-1 even after the spirochaete has been eliminated (Science 1998; 271: 703–06). Though not discussed by the authors, these findings might also raise questions over safety of immunisation against Lyme disease. It seems theoretically possible that OspA vaccines could prompt autoimmunity in susceptible individuals, though no such reaction has been observed in large trials. Kelly Morris
375
NEWS
Lyme disease vaccines are safe and effective accines against Borrelia burgdorferi have been found effective in preventing Lyme disease in two placebocontrolled trials involving more than 21 000 people from areas of the USA where Lyme disease is endemic. Lyme disease, spread by ticks, is the commonest vectorborne disease in the USA, with about 10 000 new cases being reported to the Centers for Disease Control and Prevention (Atlanta, GA) each year. The vaccines tested consist of recombinant B burgdorferi outer-surface lipoprotein A (OspA). In both trials, two doses of vaccine were given a month apart, with a booster dose at 12 months. In one trial, headed by Leonard Sigal (University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, NJ, USA), vaccine efficacy—defined as no signs or symptoms of Lyme disease and no IgG or IgM antibodies to B burgdorferi detected on western blotting—was 68% in the first year of the study, after two injections, and 92% in the second year, after the booster dose. In the other trial, led by Allen Steere (Tufts University School of Medicine, Boston, MA, USA), the efficacy of vaccine plus adjuvant—defined as no signs or symptoms of Lyme disease—
V
was 49% in the first year and 76% in the second year. Both vaccines were well tolerated, the only ill-effects being mild or moderate local and systemic reactions lasting a few days after vaccination (N Engl J Med 1998; 339: 209–15, 216–22). Arthritis and neuroborreliosis, which can be prevented with antibiotics, can develop in symptomfree infected people. Data on IgG seroconversions from Steere et al show that their vaccine was 83% effective in preventing symptomless Lyme disease in the first year and 100% effective in the second year. Sigal et al suggest that concerns about the efficacy of a vaccine that contains only a single OspA protein may be unjustified. Their vaccine “prevented Lyme disease at locations in five different states in the United States, suggesting that it provides coverage against a wide range of strains”. However, they add, no inference can be drawn about the ability of this vaccine to protect against the
European species B garinii and B afzelii. In an editorial, Roy Steigbigel and Jorge Benach (State University of New York at Stony Brook, NY, USA) say “an effective, safe, and affordable vaccine for people who live in areas where Lyme disease is endemic would be welcome” because measures to prevent exposure to ticks, such as use of insect repellents and tucking one’s trousers into one’s socks before venturing into areas where ticks are common, are “bothersome and of unknown effectiveness”. They note that the need for and frequency of booster immunisation must be investigated, since the duration of protective immunity is unknown and high antibody titres will be required to eliminate the spirochaete. “Now that the B burgdorferi genome has been sequenced, it is likely that even more effective vaccines will become available.” Dorothy Bonn
Treatment-resistant Lyme arthritis may be autoimmune disease
A
ntibiotic treatment of Lyme disease is usually effective. But a small proportion of patients develop arthritis that persists for months or years despite eradication of the causative agent, Borrelia burgdorferi. Now, evidence suggests that this treatment-resistant Lyme arthritis is an autoimmune disease, a finding that could have implications for vaccine safety. Patients with treatment-resistant Lyme arthritis have an increased frequency of the HLA allele DRB1*0401, which is also associated with rheumatoid arthritis. So, Dawn Gross (Tufts University, Boston, MA, USA) and US col-
THE LANCET • Vol 352 • August 1, 1998
leagues hypothesised that this allele might bind part of the B burgdorferi outer-surface lipoprotein A (OspA). By in-vitro and animal studies, the team identifed the specific immunodominant OspA epitope. A gene-bank search then revealed a human protein—leukocyte-function-associated antigen 1 (LFA-1)—which has sequence homology to the OspA epitope and so could act as an autoantigen. T cells from patients with treatment-resistant Lyme arthritis, but not those from patients with other chronic arthritides, reacted to whole OspA, the immunodominant OspA epitope, and LFA-1. The
authors propose that an immune reaction to B burgdorferi may upregulate LFA-1, and start a “vicious cycle”, in which T cells continue to react to LFA-1 even after the spirochaete has been eliminated (Science 1998; 271: 703–06). Though not discussed by the authors, these findings might also raise questions over safety of immunisation against Lyme disease. It seems theoretically possible that OspA vaccines could prompt autoimmunity in susceptible individuals, though no such reaction has been observed in large trials. Kelly Morris
375