Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis.
Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of Borrelia burgdorferi, the agent of Lyme disease, and the major histocompatibility complex class II allele DRB1*0401. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly related peptide epitopes. Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.
Gross
D M
DM
Department of Pathology, Tufts University, Boston, MA 02111 USA.
Forsthuber
T
T
Tary-Lehmann
M
M
Etling
C
C
Ito
K
K
Nagy
Z A
ZA
Field
J A
JA
Steere
A C
AC
Huber
B T
BT
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D016918:Arthritis, Reactive / Q000188:drug therapy / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology; D002648:Child; D003429:Cross Reactions; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes; D008074:Lipoproteins; D008193:Lyme Disease / Q000188:drug therapy / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013582:Synovial Fluid / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000954:Antigens, Surface; D001324:Autoantigens; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D016056:Immunodominant Epitopes; D008074:Lipoproteins; D016169:Lymphocyte Function-Associated Antigen-1; C072045:OspA protein