Mechanisms of HLA and Disease Associations

Tiwari, Jawahar L.; Terasaki, Paul I.

doi:10.1007/978-1-4613-8545-5_4

Cited by 117 publications

(141 citation statements)

References 23 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Only a few candidate genes have been examined extensively, and the associations found are rather weak, from a general point of view. Several studies have found an association with HLA A1, B8, DR3 in Caucasians, suggesting at least an autoimmune component in sarcoidosis, but the association is weakened by the comparison with other disorders [116].…”

Section: Concluding Thoughtsmentioning

confidence: 99%

Genetic aspects in sarcoidosis

Luisetti¹,

Beretta²,

Casali³

2000

Eur Respir J

View full text Add to dashboard Cite

Sarcoidosis is an immune-mediated, multiorgan, granulomatous disorder thought to be triggered by an intricate combination of environmental and genetic factors. Two robust lines of evidence support the hypothesis of a genetic component in the pathogenesis of sarcoidosis: racial variation in its epidemiology and familial clustering of cases. The relationship between epidemiology and environmental factors affecting variations in sarcoidosis incidence/prevalence and presentation are reviewed, as well as strategies to be pursued in the search for susceptibility genes for the disorder.Pathogenic processes leading to sarcoid granuloma formation and maintenance have prompted investigators interested in the genetics of sarcoidosis to focus mainly on major histocompatibility complex genes, and indeed a remarkable amount of data has been accumulated during the last two decades. Whilst in contrast with some autoimmune disorders a clear association between human leukocyte antigen (HLA) and sarcoidosis is still a controversial issue, there is, however, a general agreement that some HLA genes are related to phenotypic variations of the disease. Some genetic investigators have focused on T-cell receptor genes, immunoglobulin genes, angiotensin converting enzyme gene, chemokine genes and others.From a review of studies performed in different racial and ethnic groups, a reasonable suggestion arises that genetic factors are the major determinant in the racial variations in the epidemiology of the disorder. This assumption is, however, so far limited by lack of studies considering both genetic and environmental factors simultaneously. Eur Respir J 2000; 16: 768±780.

show abstract

Section: Concluding Thoughtsmentioning

confidence: 99%

Genetic aspects in sarcoidosis

Luisetti¹,

Beretta²,

Casali³

2000

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…In fact, psoriasis vulgaris is one of the few diseases showing a strong association with an antigen of the C locus. Although the association of HLA-C with psoriasis susceptibility is not absolute (20), it is intriguing to speculate that certain alleles of the S gene may contribute importantly to the pathogenesis of this common skin disorder. Preliminary studies have shown S gene-associated restriction fragment length polymorphism (RFLP).…”

Section: Methodsmentioning

confidence: 99%

“…Finally, it is of considerable interest that this gene, expressed exclusively in terminally differentiated keratinocytes, is closely linked to the HLA-C gene. Previous population studies have shown a strong association between the HLA-Cw6 allele and susceptibility to development of psoriasis vulgaris (20,50,51), a common cutaneous disease affecting -1% of the population. In fact, psoriasis vulgaris is one of the few diseases showing a strong association with an antigen of the C locus.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identification in the HLA class I region of a gene expressed late in keratinocyte differentiation.

Zhou

Chaplin

1993

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A gene designated S has been identified in the class I region of the human major histocompatibility complex. The S gene is located 160 kb telomeric of HLA-C. It is expressed at high levels as 2.2-kb and 2.6-kb mRNAs in human skin. No homologous transcripts were detected in other tissues including placenta, liver, spleen, thymus, and brain. In situ hybridization showed that S gene expression was restricted to the differentiating keratinocytes in the granular layer of the epidermis. The predicted amino acid sequence of the S protein was remarkable for its high content of serine, glycine, and proline. There were significant similarities with the amino acid sequences of loricrin, keratin 1, and keratin 10, all major components of the granular-cell layer. The selective expression of the S gene in the granular-cell layer in the epidermis suggests a role in the developmental program of differentiating keratinocytes. Furthermore, in light of the recognized association of psoriasis vulgaris, a disorder of keratinocyte proliferation, with alleles of HLA-C, this gene may contribute primarily to the pathogenesis of this common disorder.

show abstract

“…Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS With the finding of a strong association between ankylosing spondylitis and the HLA class I antigen B27 (1,2), a new era in the search for genetic markers in human diseases began, and various HLA antigens have been demonstrated to be associated with susceptibility to a large number of different diseases (for review, see ref. 3). Despite intense efforts the mechanisms involved in the associations between HLA antigens and diseases have not been unraveled.…”

mentioning

confidence: 99%

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Olerup

Hillert

Fredrikson

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

220

View full text Add to dashboard Cite

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes.Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotpe. In addition, primarily chronic progressive MS was positively associated with theDQBl restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQBI allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQBI allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers ofeach clinical form ofMS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS (4,5); i.e., the disease has a continuous progressive evolution from onset. It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4, 6), prognosis with regard to degree of disability (4, 7) and to mortality (8), and response to immunosuppression (9 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

Mechanisms of HLA and Disease Associations

Cited by 117 publications

References 23 publications

Genetic aspects in sarcoidosis

Genetic aspects in sarcoidosis

Identification in the HLA class I region of a gene expressed late in keratinocyte differentiation.

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Contact Info

Product

Resources

About