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AB0060 The association of HLA-B*51 expression with endoplasmic reticulum stress
  1. F. Cosan1,
  2. Z. Emrence2,
  3. H. Azakli2,
  4. S. Sirma2,
  5. E. Aktas-Cetin3,
  6. N. Abaci2,
  7. D. Ustek2
  1. 1Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli
  2. 2Genetics
  3. 3Immunology, Istanbul University, The Institute of Experimental Medicine (DETAE), Istanbul, Turkey

Abstract

Background Endoplasmic reticulum is an organel, where the proteins are folded. Misfolding of the proteins causes the endoplasmic reticulum stress. Unfolded protein response occurs for compansating of ER stress. It was shown the UPR molecules play role in the pathogenesis of several diseases. It was suggested, that HLA-B*27, the major genetic susceptibility for AS, is associated with UPR. HLA-B*51, which has the same Bw4 region and associated with BD, may have similar misfolding pattern.

Objectives We aimed to investigate the association between the expression of HLA-B*51 and UPR molecules.

Methods HLA-B*5 expressing monocyte cell line Thp-1 monocytes and from Thp-1 derived macrophages cell cultures were stimulated with LPS, ATP, IFN, Tunicamycin. After 8 and 24 h stimulation, mRNAs were isolated and the expression of ATF6, IRE1, PERK, XBP-1, BIP were performed with quantitative PCR. In addition PBMCs from HLA-B*51 (+), (-) and B*27(+), (-) 8 individuals were cultured, with the same agents stimulated and quantitative PCR was performed. The correlation analysis was performed with using SPSS 16.0.

Results We found that HLA-expression is correlated with IRE1 (r(12)=.957, p<0,01), PERK (r(12)=.974, p<0,01), ATF6 (r(12)=.952, p<0,01), BIP (r (12)=.610, p<0,05) in Thp-1 monocytes. A strong correlation also found with BIP (r(12)=.808, p<0,01) and ATF6 (r(12)=.626, p<0,05) expression in Thp-1 derived macrophages. In HLA-B51(+) PBMC cell culture the correlation was found with PERK (r(12)=.535, p<0,05) and ATF6 (r(12)=.622, p<0,05) expression. There was no similarity in the expression of UPR molecules in HLA-B*51 (-) cell cultures. In HLA-B*51 expressing PBMC derived macrophages, a correlation was detected between HLA and IRE1 (r(12)=.746, p<0,01), PERK (r(12)=.696, p<0,01) and ATF6 (r(12)=.558, p<0,05). Increased HLA expression was also found correlated with PERK (r(12)=.903, p<0,01) and ATF6 (r(12)=.706, p<0,01) in HLA-B*27(+) PBMC culture. In HLA-B*51 and B*27 (-) cell cultures it was no similar and strong UPR response to different stimulant agents.

Conclusions Our data reveals that it is a strong association between the expression of HLA-B*51 and spesific UPR molecules after stimulation, while the HLA-B*51 and B*27 negative cultures did not respond to stimulant agents in similar pattern. In the monocytes HLA-B*51 expression is found especially correlated with PERK and ATF6. This finding may show the role of ER stress in BD pathogenesis.

Disclosure of Interest None Declared

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