RGD Reference Report - HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis. - Rat Genome Database

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HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis.

Authors: Iliopoulou, BP  Guerau-de-Arellano, M  Huber, BT 
Citation: Iliopoulou BP, etal., Arthritis Rheum. 2009 Dec;60(12):3831-40.
RGD ID: 5147586
Pubmed: PMID:19950279   (View Abstract at PubMed)
PMCID: PMC2828865   (View Article at PubMed Central)
DOI: DOI:10.1002/art.25005   (Journal Full-text)

OBJECTIVE: Arthritis is a prominent manifestation of Lyme disease, which is caused by infection with Borrelia burgdorferi (Bb). Chronic Lyme arthritis persisting even after antibiotic treatment is linked to HLA-DRB1*0401 (DR4) and related alleles. In contrast, patients whose Lyme arthritis resolves within 3 months postinfection show an increased frequency of HLA-DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA-DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis. METHODS: We generated DR11-transgenic (DR11-Tg) mice on a murine MHCII-/- background and compared their immune response to Bb antigens with the response of DR4-Tg mice after immunization with Bb outer surface protein A (OspA) or infection with live Bb. RESULTS: T cells from OspA-immunized and Bb-infected DR11-Tg mice had defective production of interferon-gamma as compared with those from DR4-Tg mice. In contrast, DR11-Tg mice developed higher titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-Tg mice. Consistent with this observation, we found that the Bb-infected DR11-Tg mice had a decreased spirochetal burden as compared with the DR4-Tg mice, as measured by quantitative polymerase chain reaction. CONCLUSION: This study provides direct evidence that in the presence of HLA-DR11, the immune response against Bb antigens is directed toward a protective antibody response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals to the development of chronic Lyme arthritis and, eventually, the progression to antibiotic-refractory Lyme arthritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Arthritis  ISOHLA-DRB1 (Homo sapiens)5147586; 5147586 RGD 
Experimental Arthritis  IMP 5147586 RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Db1  (RT1 class II, locus Db1)

Genes (Mus musculus)
H2-Eb1  (histocompatibility 2, class II antigen E beta)

Genes (Homo sapiens)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)


Additional Information