Hla class II antigens assoiated with lupus nephritis in italian SLE patients

Marchini, Maurizio; Antonioli, R.; Lleò, Ana; Barili, Morena; Caronni, Monica; Origgi, L; Vanoli, M.; Scorza, Raffaella

doi:10.1016/s0198-8859(03)00017-x

Cited by 58 publications

(39 citation statements)

References 45 publications

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“…Although some studies suggested an association with HLA-DR2 and HLA-DR3, the two best established MHC susceptibility loci for SLE, not all studies are in agreement regarding the role of the MHC in LN. 32,33 In our study that contrasts patients with LN with patients with lupus without nephritis, modest associations were observed with both of these MHC class II alleles (as assessed by proxies). Analyses conditioned on rs9271366 and rs2187668 indicate that loci outside of MHC class II genes may also contribute to LN risk, as seen in other studies of SLE.…”

Section: Discussionmentioning

confidence: 55%

Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

Chung

Brown

Williams

et al. 2014

Journal of the American Society of Nephrology

119

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Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, .1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P54.5310 27 ), 16p12 (SLC5A11;P55.1310 27 ), 6p22 (ID4; P57.4310 27 ), and 8q24.12 (HAS2, SNTB1; P51.1310 26 ). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P53.7310 25 , respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P58.5310 26 ). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci.

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Section: Discussionmentioning

confidence: 55%

Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

Chung

Brown

Williams

et al. 2014

Journal of the American Society of Nephrology

119

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“…20 Like other HLA class II alleles, the presence or absence of HLA DR15 has been implicated in several autoimmune states. [21][22][23][24][25][26][27][28][29][30][31][32][33] The precise relevance of these associations is unknown in the context of BMT.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Battiwalla

Hahn

Radovic

et al. 2006

Blood

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The DR15 allele at the HLA DRB1 locus is a marker for immune-mediated bone marrow failure syndromes. We hypothesized that HLA DR15 plays a role in T-cell interactions with hematopoiesis and investigated the role of HLA DR15 on graftversus-host disease (GVHD) and graftversus-leukemia effects in HLA-matched allogeneic blood or marrow transplantation (BMT) performed for myeloid malignancies. We performed a retrospective analysis of 119 consecutive related and 48 consecutive unrelated allogeneic BMT for myeloid malignancies treated between 1991 and 2005 to investigate the influence of HLA DR15 on overall survival (OS), progression-free survival (PFS), and incidence of grades II to IV acute GVHD. HLA DR15 was determined by either molecular (n ‫؍‬ 108) or serologic (n ‫؍‬ 59) methods. The incidence of HLA DR15 was similar to the general white population (35/167 ‫؍‬ 21%). There were no significant differences in transplantation characteristics between the HLA DR15-positive and -negative groups. There was no significant difference in chronic GVHD, OS, or PFS between the HLA DR15-positive versus-negative groups in any disease or donor relation subgroups. The HLA DR15-positive group experienced a significantly lower incidence of acute GVHD grades II to IV: 23% versus 42% (P ‫؍‬ .041). These results suggest that HLA DR15 reduces the risk of acute GVHD. (Blood.

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“…It is becoming increasingly clear that patterns of LD vary depending on the HLA background [Ahmad et al, 2003a;Blomhoff et al, 2006]. More recently, this LD structure has come under additional scrutiny because several linkage scans and association-mapping studies of autoimmune diseases [Davies et al, 1994;Marchini et al, 2003;Harbo et al, 2004;Marrosu et al, 2004;Oksenberg et al, 2004] and infectious diseases [Hill et al, 1991;Carrington and O'Brien, 2003] have indicated an involvement of the MHC region in disease susceptibility. A common finding that has emerged with diseases linked to the MHC is that an extended haplotype, rather than a single variant shows association.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia

Morar¹,

Schwab

Albus³

et al. 2006

American J of Med Genetics Pt B

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The association of the tumor necrosis factor alpha (TNFalpha) -G308A promoter polymorphism with schizophrenia has complemented clinical findings of increased levels of the TNFalpha cytokine in schizophrenic patients, with some support for a functional consequence of the variant. Our previous studies of genetic causes in schizophrenia supported findings of linkage to the major histocompatibility complex (MHC) region where the TNFalpha gene is located as well as association with the -G308A promoter polymorphism. While the common G-allele shows association in our sample, association with the A-allele has been reported by other groups. This suggests linkage disequilibrium (LD) rather than direct involvement in the disorder. In order to define LD of DNA variants with the disorder in this area, we analyzed 36 SNPs in a 165-kb region around this polymorphism. We detected nominally significant associations (P < 0.05) of three markers (including the -G308A promoter polymorphism) and multiple haplotypes with schizophrenia in our sample of 204 families (79 sib-pairs and 125 trios). The association is largely restricted to a 30 kb high LD region/block and should assist in the identification of a schizophrenia susceptibility gene within the block or elsewhere in the MHC.

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Hla class II antigens assoiated with lupus nephritis in italian SLE patients

Cited by 58 publications

References 45 publications

Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia

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