Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE
© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology..
OBJECTIVES: Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1* alleles and thrombosis in SLE. Conventional aPL were included for comparison.
METHODS: We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified.
RESULTS: aPS/PT antibodies associated positively with HLA-DRB1*13 [odds ratio (OR) 2.7, P = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1* alleles. HLA-DRB1*13, but not DRB1*04, remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03, on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides.
CONCLUSIONS: HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Rheumatology (Oxford, England) - 62(2023), 2 vom: 01. Feb., Seite 924-933 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Elbagir, Sahwa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.02.2023 Date Revised 14.03.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/rheumatology/keac327 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341650056 |
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| 100 | 1 | |a Elbagir, Sahwa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 03.02.2023 | ||
| 500 | |a Date Revised 14.03.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. | ||
| 520 | |a OBJECTIVES: Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1* alleles and thrombosis in SLE. Conventional aPL were included for comparison | ||
| 520 | |a METHODS: We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified | ||
| 520 | |a RESULTS: aPS/PT antibodies associated positively with HLA-DRB1*13 [odds ratio (OR) 2.7, P = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1* alleles. HLA-DRB1*13, but not DRB1*04, remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03, on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides | ||
| 520 | |a CONCLUSIONS: HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a thrombosis | |
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| 650 | 7 | |a Phosphatidylserines |2 NLM | |
| 650 | 7 | |a beta 2-Glycoprotein I |2 NLM | |
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| 700 | 1 | |a Grosso, Giorgia |e verfasserin |4 aut | |
| 700 | 1 | |a Zickert, Agneta |e verfasserin |4 aut | |
| 700 | 1 | |a Gunnarsson, Iva |e verfasserin |4 aut | |
| 700 | 1 | |a Mahler, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Svenungsson, Elisabet |e verfasserin |4 aut | |
| 700 | 1 | |a Rönnelid, Johan |e verfasserin |4 aut | |
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