Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy

Vance Matthews, C.S. Witt, Martyn French, H.K.G. Machulla, E.G. De La Concha, Karey Cheong, P. Vigil, P.N. Hollingsworth, K.J. Warr, Frank Christiansen, Patricia Price

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA -B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a Susceptibility locus in the central MHC. Provisional mapping within this region is discussed.
Original languageEnglish
Pages (from-to)424-433
JournalHuman Immunology
Volume63
DOIs
Publication statusPublished - 2002

Fingerprint

IgA Deficiency
Major Histocompatibility Complex
Immunoglobulin A
Genes
Haplotypes
Alleles
Microsatellite Repeats
HLA-B14 Antigen
HLA-A1 Antigen
HLA-B8 Antigen
HLA-DR3 Antigen
Single Nucleotide Polymorphism

Cite this

Matthews, Vance ; Witt, C.S. ; French, Martyn ; Machulla, H.K.G. ; De La Concha, E.G. ; Cheong, Karey ; Vigil, P. ; Hollingsworth, P.N. ; Warr, K.J. ; Christiansen, Frank ; Price, Patricia. / Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy. In: Human Immunology. 2002 ; Vol. 63. pp. 424-433.
@article{f1244f31694540de99016bd599572dd5,
title = "Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy",
abstract = "This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA -B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a Susceptibility locus in the central MHC. Provisional mapping within this region is discussed.",
author = "Vance Matthews and C.S. Witt and Martyn French and H.K.G. Machulla and {De La Concha}, E.G. and Karey Cheong and P. Vigil and P.N. Hollingsworth and K.J. Warr and Frank Christiansen and Patricia Price",
year = "2002",
doi = "10.1016/S0198-8859(02)00383-X",
language = "English",
volume = "63",
pages = "424--433",
journal = "Human Immunology",
issn = "0198-8859",
publisher = "Academic Press",

}

Matthews, V, Witt, CS, French, M, Machulla, HKG, De La Concha, EG, Cheong, K, Vigil, P, Hollingsworth, PN, Warr, KJ, Christiansen, F & Price, P 2002, 'Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy' Human Immunology, vol. 63, pp. 424-433. https://doi.org/10.1016/S0198-8859(02)00383-X

Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy. / Matthews, Vance; Witt, C.S.; French, Martyn; Machulla, H.K.G.; De La Concha, E.G.; Cheong, Karey; Vigil, P.; Hollingsworth, P.N.; Warr, K.J.; Christiansen, Frank; Price, Patricia.

In: Human Immunology, Vol. 63, 2002, p. 424-433.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Central MHC Genes Affect IgA Levels in the Human: Reciprocal Effects in IgA Deficiency and IgA Nephropathy

AU - Matthews, Vance

AU - Witt, C.S.

AU - French, Martyn

AU - Machulla, H.K.G.

AU - De La Concha, E.G.

AU - Cheong, Karey

AU - Vigil, P.

AU - Hollingsworth, P.N.

AU - Warr, K.J.

AU - Christiansen, Frank

AU - Price, Patricia

PY - 2002

Y1 - 2002

N2 - This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA -B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a Susceptibility locus in the central MHC. Provisional mapping within this region is discussed.

AB - This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA -B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a Susceptibility locus in the central MHC. Provisional mapping within this region is discussed.

U2 - 10.1016/S0198-8859(02)00383-X

DO - 10.1016/S0198-8859(02)00383-X

M3 - Article

VL - 63

SP - 424

EP - 433

JO - Human Immunology

JF - Human Immunology

SN - 0198-8859

ER -