ASSOCIATION OF CHRONIC LYME ARTHRITIS WITH HLA-DR4 AND HLA-DR2 ALLELES

A small percentage of patients infected with Borrelia burgdorferi have chronic Lyme arthritis that does not respond to antibiotic therapy. To learn whether genetically determined variations in the host immune response might account for such outcomes, we determined the immunogenetic profiles of 130 patients with various manifestations of Lyme disease. Of the 80 patients with arthritis, 57 percent of those with chronic arthritis (12 to 48 months in duration) had the HLA-DR4 specificity; only 23 percent of those with arthritis of moderate duration (6 to 11 months) and only 9 percent of those with arthritis of short duration (1 to 5 months) had this specificity (P = 0.003). After the HLA-DR4-positive patients were excluded from each group, a secondary association was noted with HLA-DR2, which was found in 75 percent of the remaining patients with chronic arthritis and in 50 percent of those with arthritis of moderate duration, but in only 20 percent of those with arthritis of short duration (P = 0.023). Altogether, 25 of the 28 patients with chronic arthritis (89 percent) had HLA-DR2 or HLA-DR4, or both, as compared with 27 percent of those with arthritis of short duration (relative risk, 22; P = 0.00006). These HLA specificities appeared to act as independent, dominant markers of susceptibility. Nucleotide-sequence typing, performed in five patients with chronic arthritis, identified the HLA-DR2 allele as Dw2 (DRβ1*1501), and the HLA-DR4 alleles as Dw4, Dw14, and Dw13 (DRβ1*0401, DRβ1*0404, and DRβ1*0403, respectively). The presence of HLA-DR4 in patients with arthritis was associated with a lack of response to antibiotic therapy (P = 0.01). Particular Class II major histocompatibility genes determine a host immune response to B. burgdorferi that results in chronic arthritis and lack of response to antibiotic therapy. (N Engl J Med 1990; 323:219–23.) LYME disease, which is caused by the tick-borne spirochete Borrelia burgdorferi, often begins with a characteristic skin lesion, erythema migrans, and is commonly followed by neurologic, cardiac, or joint abnormalities of variable duration.1 The involvement of the joints, which is seen in about 80 percent of patients, often begins with migratory joint pain and is frequently followed months later by brief attacks of oligoarthritis.2 During the second and third years of illness, the episodes of arthritis may last longer, and in about 10 percent of patients joint involvement becomes chronic, sometimes with erosion of cartilage and bone.2,3 The synovial. © 1990, Massachusetts Medical Society. All rights reserved.