Mechanisms of genetic susceptibility to type I diabetes: beyond HLA

Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4

1995 • 2,842 citations

T cell tolerance by clonal elimination in the thymus

1987 • 2,248 citations

Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease

2003 • 2,181 citations

AU-rich elements: characterization and importance in mRNA degradation

1995 • 1,936 citations

Haplotype tagging for the identification of common disease genes

2001 • 1,188 citations

Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self

2001 • 1,043 citations

Formation of mRNA 3′ Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis

1999 • 1,016 citations

The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes

1997 • 931 citations

Negative selection of lymphocytes

1994 • 810 citations

Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus

1997 • 806 citations

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

1996 • 794 citations

Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus

1995 • 749 citations

A Polymorphic Locus Near the Human Insulin Gene Is Associated with Insulin-dependent Diabetes Melliitus

1984 • 744 citations

Evidence for a differential avidity model of T cell selection in the thymus

1994 • 679 citations

CTLA-4 Gene Polymorphism at Position 49 in Exon 1 Reduces the Inhibitory Function of CTLA-4 and Contributes to the Pathogenesis of Graves’ Disease

2000 • 508 citations

A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria

1999 • 490 citations

Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

1999 • 442 citations

CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population.

1995 • 426 citations

Parental genomic imprinting of the human IGF2 gene

1993 • 422 citations

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

1997 • 408 citations

Lymphoproliferation in CTLA-4–Deficient Mice Is Mediated by Costimulation-Dependent Activation of CD4 + T Cells

1997 • 405 citations

The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription

1995 • 383 citations

CTLA-4: a negative regulator of autoimmune disease.

1996 • 382 citations

Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility

1991 • 378 citations

CTLA-4 gene expression is influenced by promoter and exon 1 polymorphisms

2001 • 359 citations

Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Regulates the Unfolding of Autoimmune Diabetes

1998 • 295 citations

HUMAN TYPE 1 DIABETES AND THE INSULIN GENE: Principles of Mapping Polygenes

1996 • 291 citations

A polymorphism in the human cytotoxic T-lymphocyte antigen 4 ( CTLA4 ) gene (exon 1 +49) alters T-cell activation

2002 • 288 citations

Insulin‐specific T cells are a predominant component of islet infiltrates in pre‐diabetic NOD mice

1994 • 279 citations

A Common Autoimmunity Predisposing Signal Peptide Variant of the Cytotoxic T-lymphocyte Antigen 4 Results in Inefficient Glycosylation of the Susceptibility Allele

2002 • 278 citations

Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR

1993 • 271 citations

Insulin Expression Levels in the Thymus Modulate Insulin-Specific Autoreactive T-Cell Tolerance

2002 • 260 citations

A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells

1999 • 257 citations

Transgenic Expression of Mouse Proinsulin II Prevents Diabetes in Nonobese Diabetic Mice

1997 • 248 citations

A Native Soluble Form of CTLA-4

2000 • 238 citations

CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis.

1996 • 232 citations

Cutting Edge: A Soluble Form of CTLA-4 in Patients with Autoimmune Thyroid Disease

2000 • 227 citations

T-cell tolerance toward a transgenic beta-cell antigen and transcription of endogenous pancreatic genes in thymus.

1994 • 223 citations

Acceleration of type 1 diabetes mellitus in proinsulin 2–deficient NOD mice

2003 • 221 citations

Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31–q33

1995 • 211 citations

A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus

1984 • 205 citations

CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population

1995 • 203 citations

A CTLA-4 gene polymorphism at position −318 in the promoter region affects the expression of protein

2002 • 198 citations

Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo.

1993 • 191 citations

IDDM2-VNTR-encoded Susceptibility to Type 1 Diabetes: Dominant Protection and Parental Transmission of Alleles of the Insulin Gene-linked Minisatellite Locus

1996 • 165 citations

The Development of Graves’ Disease and theCTLA-4Gene on Chromosome 2q33¹

1999 • 154 citations

Association of CTLA‐4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population

2001 • 154 citations

Association of CTLA-4 Gene A-G Polymorphism (IDDM12 Locus) With Acute-Onset and Insulin-Depleted IDDM as Well as Autoimmune Thyroid Disease (Graves' Disease and Hashimoto's Thyroiditis) in the Japanese Population

1998 • 147 citations

The CTLA-4 gene is associated with multiple sclerosis

1999 • 146 citations

Abnormal expression of CTLA-4 by T cells from patients with myasthenia gravis: effect of an AT-rich gene sequence

2002 • 143 citations

CTLA-4 gene polymorphisms in systemic lupus erythematosus: a highly significant association with a determinant in the promoter region

2002 • 143 citations

CTLA‐4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis

1998 • 140 citations

Insulin gene region–encoded susceptibility to type 1 diabetes is not restricted to HLA–DR4–positive individuals

1992 • 138 citations

Diabetogenic T-Cell Clones

1996 • 127 citations

Imprinted and Genotype-specific Expression of Genes at theIDDM2Locus in Pancreas and Leucocytes

1996 • 115 citations

Genetic and physical mapping of a type 1 diabetes susceptibility gene (IDDM12) to a 100-kb phagemid artificial chromosome clone containing D2S72-CTLA4-D2S105 on chromosome 2q33.

2000 • 113 citations

Markers on Distal Chromosome 2q Linked to Insulin-Dependent Diabetes Mellitus

1996 • 111 citations

Regulation of insulin gene expression by the IDDM associated, insulin locus haplotype

1995 • 106 citations

CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers

1997 • 105 citations

Increased Expression of Soluble Cytotoxic T‐Lymphocyte‐Associated Antigen‐4 Molecule in Patients with Systemic Lupus Erythematosus

2003 • 102 citations

The Development of Graves' Disease and the CTLA-4 Gene on Chromosome 2q33

1999 • 102 citations

Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells

2000 • 102 citations

Relation of three polymorphisms of the CTLA-4 gene in patients with Graves’ disease

2002 • 96 citations

Insulin Gene Region-Encoded Susceptibility to IDDM Maps Upstream of the Insulin Gene

1995 • 91 citations

Class III Alleles of the Variable Number of Tandem Repeat Insulin Polymorphism Associated with Silencing of Thymic Insulin Predispose to Type 1 Diabetes

2001 • 86 citations

Genetic association of Ctla-4 to myasthenia gravis with thymoma

1998 • 86 citations

Localization of a Type I Diabetes Susceptibility Locus to the Variable Tandem Repeat Region Flanking the Insulin Gene

1993 • 86 citations

CTLA-4 gene polymorphism may modulate disease in Japanese multiple sclerosis patients

1999 • 83 citations

Complete Sequence Determination of the Mouse and Human CTLA4 Gene Loci: Cross-Species DNA Sequence Similarity beyond Exon Borders

1999 • 76 citations

The Search for IDDM Susceptibility Genes: The Next Generation

1996 • 71 citations

CTLA-4 Gene Polymorphisms in Tunisian Patients with Graves' Disease

2001 • 62 citations

Assembly and Annotation of Human Chromosome 2q33 Sequence Containing the CD28, CTLA4, and ICOS Gene Cluster: Analysis by Computational, Comparative, and Microarray Approaches

2001 • 61 citations

Technical Note: Linkage Disequilibrium and Disease-Associated CTLA4 Gene Polymorphisms

2001 • 59 citations

Regulation of gene expression for translation initiation factor eIF-2α: importance of the 3′ untranslated region

1996 • 57 citations

Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice

1997 • 55 citations

CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis

2000 • 54 citations

Genetic analysis of the hypervariable region flanking the human insulin gene.

1986 • 49 citations

Analysis of a 1963-bp polymorphic region flanking the human insulin gene

1984 • 48 citations

CTLA‐4 gene A–G polymorphism and childhood Graves’ disease

2002 • 45 citations

Diabetogenic T-cell clones

1996 • 43 citations

Divergence between Genetic Determinants ofIGF2Transcription Levels in Leukocytes and ofIDDM2-Encoded Susceptibility to Type 1 Diabetes¹

1998 • 40 citations

CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis

2002 • 38 citations

Polymorphisms of the CTLA-4 exon 1 and promoter gene in systemic lupus erythematosus

2001 • 37 citations

The search for IDDM susceptibility genes: the next generation

1996 • 33 citations

Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of the insulin gene

1996 • 29 citations

Insulin gene region-encoded susceptibility to IDDM maps upstream of the insulin gene

1995 • 28 citations

Divergence between Genetic Determinants of IGF2 Transcription Levels in Leukocytes and of IDDM2-Encoded Susceptibility to Type 1 Diabetes

1998 • 27 citations

The Length of the CTLA-4 Microsatellite (AT)_N-Repeat Affects the Risk for Type 1 Diabetes: For the Swedish Childhood Diabetes Study Group

2000 • 26 citations

Localization of a type I diabetes susceptibility locus to the variable tandem repeat region flanking the insulin gene

1993 • 24 citations

Class III Alleles of the Variable Number of Tandem Repeat Insulin Polymorphism Associated with Silencing of Thymic Insulin Predispose to Type 1 Diabetes

2001 • 18 citations