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| Identifier |
000341417 |
| Title |
Μελέτη πολυμορφισμών και έκφρασης του ανοσορρυθμιστικού υποδοχέα PD-1 (Programmed Death-1) σε ασθενείς με συστηματικό ερυθηματώδη λύκο |
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Author
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Μπερτσιάς, Γεώργιος
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Thesis advisor
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Μπούμπας, Δημήτριος
Γουλιέλμος, Γεώργιος
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| Abstract |
Peripheral immune toleranace is important for the functional restriction of autoreactive lymphocytes that escape from central lymphoid organs. Programmed death-1 (PD-1) is expressed on activated T- and B-lymphocytes and results in decreased proliferation, cytokine production and anergy upon engagement with its specific ligands (PD-1 ligands). Murine studies have indicated a crucial role for PD-1 in maintenance of peripheral tolerance and transgenic strains that lack PD-1 (PD-1 knock-out) develop various autoimmune disorders. Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease in humans and is characterized by autoreactive lymphocytes and production of autoantibodies. We examined the frequency of single-nucleotide polymorphisms (SNPs) in the PD-1 gene in patients with SLE by PCR-RFLP, and the expression of PD-1 on peripheral blood mononuclear cells (resting and activated) by flow cytometry. An increased frequency of the PD1.3 (7146G/A) – but not the PD1.5 (7765C/T) SNPs was found in SLE patients compared to healthy controls (33% versus 18%, p=0.005). Patients with active SLE had increased percentage of peripheral PD-1+ CD4+ T lymphocytes (2.4 ± 0.2% versus 1.8 ± 0.2% in healthy controls, p=0.029) and increased percentage of activated PD-1+ CD4+CD25+ T lymphocytes (3.4 ± 0.4% versus 2.1 ± 0.2%, p=0.019) and PD-1+ CD4+CD69+ T lymphocytes (4.6 ± 0.6% versus 3.2 ± 0.3%, p=0.06). In contrast, expression of PD-1 ligand 1 on peripheral Τ-, Β-lymphocytes and monocytes did not differ between SLE patients and healthy controls. SLE patients with active disease who carried the PD1.3 polymorphism had decreased percentage of PD-1+ CD3+ T lymphocytes (1.3 ± 0.3% versus 2.4 ± 0.5%, p=0.09) and PD-1+ CD19+ B lymphocytes (4.2 ± 0.9% versus 2.0 ± 0.6%, p=0.07), compared to patients who did not. Stimulation of peripheral T lymphocytes with PMA-ionomycin demonstrated increased expression of PD-1 in SLE patients who carried the PD1.3 polymorphism. Our results indicate an important role for the PD-1/PD-1 ligands pathway in regulation of peripheral tolerance in patients with SLE and form the basis for the study of possible defects in expression and function of PD-1 in patients with autoimmune disease.
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| Physical description |
36 σ. : πιν. ; 30 εκ. |
| Language |
Greek |
| Subject |
Autoimmune Diseases immunology |
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Immune Tolerance |
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Lupus Erythematosus, Systemic |
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Ανοσολογική ανοχή |
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Αυτοάνοσα νοσήματα Ανοσολογία |
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Λύκος ερυθηματώδης, Συστηματικός |
| Issue date |
2006-08-04 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Notes |
Μεταπτυχιακό πρόγραμμα σπουδών:"Γενετική και κυτταρική αιτιολογία, διαγνωστική και θεραπευτική του ανθρώπου". |
| Views |
186 |
Μελέτη πολυμορφισμών και έκφρασης του ανοσορρυθμιστικού υποδοχέα PD-1 (Programmed Death-1) σε ασθενείς με συστηματικό ερυθηματώδη λύκο
