Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan

Lu, Ling‐Ying; Ding, Wei; Fici, D; Deulofeut, Richard; Cheng, He‐Hsiung; Cheu, Ching‐Cheng; Sung, Ping-Kuang; Schur, Peter H.; Fraser, Patricia A.

doi:10.1002/art.1780400619

Cited by 55 publications

(43 citation statements)

References 33 publications

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“…Complex factors are thought to play various roles in the pathogenesis of SLE. For instance, serological studies have long suggested an association between certain human leukocyte antigens and SLE or autoantibody production [13, 14, 15, 16]. On the other hand, it is still controversial which cytokines play roles in the pathogenesis of SLE.…”

Section: Discussionmentioning

confidence: 99%

Vitamin-D Receptor Genotype and Renal Disorder in Japanese Patients with Systemic Lupus erythematosus

Ozaki¹,

Nomura

Nagahama³

et al. 2000

Nephron

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Background/Aims: It is known that allelic variants of the gene encoding the vitamin-D receptor (VDR) detected by BsmI increase the risk of some advanced malignant tumors, suggesting that such variants may cause functional differences in 1,25(OH)₂ vitamin D₃. We examined the VDR genes of Japanese systemic lupus erythematosus (SLE) patients, to determine whether different genotypes are correlated with SLE or its criteria. Methods: VDR genotyping of 58 unrelated Japanese SLE patients was performed based on polymerase chain reaction-restriction fragment length polymorphism (RFLP). Following amplification, products were digested with BsmI. The RFLPs were coded as Bb, where the uppercase letter signifies the absence of the digested site and the lowercase letter signifies the presence of the site. Results: The frequency of the VDR BB genotype was significantly higher in SLE patients (15.5%, n = 9/58, p < 0.0001) than in controls (5.7%, n = 5/87). Furthermore, a larger proportion of bb individuals was observed among patients with nephrotic syndrome (61.5%, n = 8/13) than among SLE patients without renal dysfunction (35.7%, n = 10/28). There was a significant tendency for the population of patients with the bb genotype to be correlated with that of patients with renal dysfunction (p = 0.0304). Conclusion: These findings suggest that the BB genotype might trigger the development of SLE, and that the bb genotype is associated with lupus nephritis.

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Section: Discussionmentioning

confidence: 99%

Vitamin-D Receptor Genotype and Renal Disorder in Japanese Patients with Systemic Lupus erythematosus

Ozaki¹,

Nomura

Nagahama³

et al. 2000

Nephron

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“…Depending on the ethnic background of the study populations and the assay techniques, a wide variety of associations has been described. In Caucasians, the most consistent positive class II major histocompatibility complex (MHC) association with SLE is HLA-DR3 (1-6), whereas in Asian populations, HLA-DR1 and DR2 haplotypes predominate (7)(8)(9).…”

mentioning

confidence: 99%

TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus

Rood

Krugten

Zanelli

et al. 2000

Arthritis & Rheumatism

167

104

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Objective. To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE).Methods. TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes.Results. The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRB1*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation.Conclusion. TNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.

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“…This is strongly supported by the linked association of genes encoded within the H-2 z locus with susceptibility to lupus in several mouse models, including New Zealand hybrid mice and their derivatives (5,6). The disease association with certain HLA haplotypes, including HLA-DR2 and HLA-DR3 (7)(8)(9)(10)(11) and HLA-B8 (11), and certain complement (12) and TNF polymorphisms (13) has been reported in human lupus.…”

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confidence: 99%

HLA-DR Modulates Autoantibody Repertoire, But Not Mortality, in a Humanized Mouse Model of Systemic Lupus Erythematosus

Paisansinsup

Vallejo

Luthra

et al. 2001

The Journal of Immunology

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To evaluate the disease-modulating role of HLA-DR2 and DR3 molecules, which have been associated with systemic lupus erythematosus, a humanized mouse model was examined. HLA-DR2 (DRB1*1502)- and DR3 (DRB1*0301)-transgenic mice were backcrossed to the New Zealand Mixed 2410 (NZM 2410, H2z) strain. Seventh generation DR2 and DR3 transgene-positive animals along with their transgene-negative littermates and the parental strain NZM2410 were monitored for proteinuria, azotemia, autoantibody production, development of nephritis, and mortality. The results showed no significant differences in proteinuria, azotemia, or mortality between the backcrosses with and without HLA-DR2 or HLA-DR3. However, the genetic analysis of different backcrosses showed that heterozygosity at the endogenous H2-E locus (Ez/Eb) was strongly linked with acceleration of lupus nephritis in both HLA-DR2 and HLA-DR3 transgenics. More importantly, the presence of the HLA-DR2, but not the HLA-DR3, transgene significantly enhanced the production of anti-dsDNA, but not anti-ssDNA, anti-histone-dsDNA complex, or anti-histone, Abs. In contrast, neither HLA-DR2 nor HLA-DR3 influenced the development of glomerulonephritis or the degree of immune complex deposition. Moreover, nephritic kidneys from mice with and without HLA-DR2 or HLA-DR3 transgenes showed similar patterns of cytokine expression. Collectively, these findings provide molecular evidence that the association of HLA-DR2 or HLA-DR3 with lupus susceptibility is related to the type of autoantibody rather than to disease mortality. The use of a humanized mouse model provides a way of dissecting the roles of human MHC genes in systemic lupus erythematosus pathogenesis.

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Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan

Cited by 55 publications

References 33 publications

Vitamin-D Receptor Genotype and Renal Disorder in Japanese Patients with Systemic Lupus erythematosus

Vitamin-D Receptor Genotype and Renal Disorder in Japanese Patients with Systemic Lupus erythematosus

TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus

HLA-DR Modulates Autoantibody Repertoire, But Not Mortality, in a Humanized Mouse Model of Systemic Lupus Erythematosus

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