Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome

Tolva, Johanna; Paakkanen, Riitta; Jarva, Hanna; Pussinen, Pirkko J.; Havulinna, Aki S.; Salomaa, Veikko; Sinisalo, Juha; Lokki, Marja-Liisa

doi:10.1016/j.atherosclerosis.2017.09.023

Cited by 2 publications

(3 citation statements)

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“…However, recently also neurobiological processes of synaptogenesis have been shown to be dependent on HLA and non‐HLA molecules of the MHC . Till date, over 160 different diseases associated with MHC have been identified by candidate gene analyses, gene expression, and proteomic analyses, with genome‐wide association studies (GWAS), Immunochip, and phenome‐wide association studies (PheWAS) (Table ) . Importantly, in HLA‐associated diseases, population‐based variation in the frequencies of risk/protective alleles and haplotypes is significant and should be included in phenotype characterization of disease subgroups and interventional trials …”

Section: Hla and Disease Associationsmentioning

confidence: 99%

“…[50][51][52] Till date, over 160 different diseases associated with MHC have been identified by candidate gene analyses, gene expression, and proteomic analyses, with genome-wide association studies (GWAS), Immunochip, and phenome-wide association studies (PheWAS) ( Table 4). 29,[52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] Importantly, in HLA-associated diseases, population-based variation in the frequencies of risk/protective alleles and haplotypes is significant and should be included in phenotype characterization of disease subgroups and interventional trials. 69 We have challenged the drawbacks of the HLA-DRB1 imputation in combining GWA SNP results with the allele copy numbers of HLA-DRB1*01 determined by genomic quantitative polymerase chain reaction (PCR) as a priori candidate gene associated with the complex disease of coronary artery disease.…”

Section: Hla and Disease Associationsmentioning

confidence: 99%

“…In Goodpasture's kidney disease, the mechanism of the HLA-DRB1*01 mediated protection has been revealed. The conformation of HLA-DRB1*01 presenting immunodominant autoreactive peptide Soluble HLA II Elevated serum levels Observed in acute phases of multiple sclerosis, rheumatoid arthritis and autoimmune hepatitis, smoking and inflammation in rheumatoid arthritis [59][60][61][62]67 Decreased serum levels Observed in end-stage heart disease, severe sepsis and with melanoma progression [63][64][65] Both susceptible and protective associations HLA-DRB1*15 Diabetes mellitus type I and neurological conditions (see text) 74,86,87 Abbreviations: eQTLs, expression quantitative trait loci; MHC, major histocompatibility complex; SNP, single nucleotide polymorphism.…”

Section: Hla and Disease Associationsmentioning

confidence: 99%

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The complexity and diversity of major histocompatibility complex challenge disease association studies

Lokki

Paakkanen

2018

HLA

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The major histocompatibility complex (MHC; 6p21.3) contains the most polymorphic genes, the most gene dense parts, and the highest diversity of functional gene clusters of the human genome. The clusters form haplotypes, which differ in linkage disequilibrium and show large variations in strength and extent between populations. Haplotype cis‐ and trans‐expression quantitative trait loci have increased the knowledge of regulatory interactions between multiple MHC genes. The detailed haplotype data offer a reference for future studies in immune‐mediated diseases and may unravel disease associations in conditions traditionally considered not to be immunologic. This article aims to describe the structural and functional variations of the MHC genes and haplotypes and their role on selected immune‐mediated diseases. In immune‐/inflammation‐mediated complex diseases, hundreds of common variants influence the development of the disease trait, but the individual variants have small effects on the disease phenotypes as seen in genome‐wide association studies. The genetic influence may still be significant on the cellular or molecular level. Nonetheless, the HLA alone is not sufficient as a susceptible genetic background to deduce the disease. For a comprehensive insight of the disease mechanisms, both immunological and genome assays methods are required.

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Section: Hla and Disease Associationsmentioning

confidence: 99%

Section: Hla and Disease Associationsmentioning

confidence: 99%

Section: Hla and Disease Associationsmentioning

confidence: 99%

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The complexity and diversity of major histocompatibility complex challenge disease association studies

Lokki

Paakkanen

2018

HLA

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Soluble HLA-I and HLA-II Molecules Are Potential Prognostic Markers of Progression of Systemic and Local Inflammation in Patients with COPD

Kubysheva

Soodaeva²,

Novikov

et al. 2018

Disease Markers

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Soluble molecules of the major histocompatibility complex play an important role in the development of various immune-mediated diseases. However, there is not much information on the participation of these proteins in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of our work was to determine the content of soluble molecules of the major histocompatibility complex of classes I and II (sHLA-I and sHLA-II) in the exhaled breath condensate (EBC) and in the blood serum in patients with moderate to severe COPD during the exacerbation and stable phase. We investigated 105 patients (male) with COPD aged 46–67 and 21 healthy nonsmoking volunteers (male) comparable in age. The content of sHLA-I and sHLA-II molecules was studied using ELISA. We found an increase in the level of sHLA-I and sHLA-II molecules in EBC, as well as an enhancement in the serum content of sHLA-II in all the examined COPD patients compared to healthy nonsmoking volunteers. The revealed negative correlation between the serum concentration of sHLA-II and values of FEV1 and FEV1/FVC in all examined patients with COPD gives a possibility to consider the content of these proteins as an additional systemic marker of disease severity. The maximum endobronchial and serum concentrations of sHLA-I and sHLA-II were detected in patients with severe COPD during the exacerbation. The negative associations between the content of these molecules in EBC and serum and the parameters of lung function in patients with severe COPD were established. These findings suggest a pathogenetic role of sHLA-I and sHLA-II molecules in the mechanisms of the development and progression of local and systemic inflammation in COPD.

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Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome

Cited by 2 publications

References 31 publications

The complexity and diversity of major histocompatibility complex challenge disease association studies

The complexity and diversity of major histocompatibility complex challenge disease association studies

Soluble HLA-I and HLA-II Molecules Are Potential Prognostic Markers of Progression of Systemic and Local Inflammation in Patients with COPD

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