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62 Acquired ficolin...
62 Acquired ficolin-3 deficiency in patients with Systemic Lupus Erythematosus
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- Lindelöf, Linnea (författare)
- Uppsala University, Sweden
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- Dahlqvist, Solbritt Rantapää (författare)
- Umeå University, Sweden
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- Lundtoft, Christian (författare)
- Uppsala University, Sweden
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- Nilsson Ekdahl, Kristina (författare)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC
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- Nilsson, Bo (författare)
- Uppsala University, Sweden
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- Gunnarsson, Iva (författare)
- Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden
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- Svenungsson, Elisabet (författare)
- Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden
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Eriksson, Oskar (författare)
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 228:5, s. 152515-152515
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background: Ficolin-3 is the main initiator of the lectin pathway in humans. Case reports of ficolin-3 deficient patients have suggested that ficolin-3 deficiency may be enriched in patients with Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease where complement plays an important role. Therefore, this study aimed to investigate the activity levels of ficolin-3 and to identify potential ficolin-3 deficient individuals in two Swedish SLE cohorts.Methods: Serum or plasma samples from SLE patients (n=810) and matched controls (n=566) were collected from the Karolinska Institute (KI) and Umeå University Hospital. The ficolin-3 activity levels were measured by an in-house developed functional ELISA with a pooled normal human serum sample as a reference. Serial samples were analyzed for ficolin-3 deficient patients when available. Sequencing data were analyzed for FCN3 frame-shift mutation +1637delC (rs532781899) and other potential loss-of-function (LoF) variants.Results: This screening revealed that the level of ficolin-3 activity varies largely in patients with SLE. The activity levels also show that SLE patients seem to generally have elevated ficolin-3 activity compared to the control group (p<0.0001). Out of 810 patients with SLE, four patients were determined to be ficolin-3 deficient. For two of these patients, the ficolin-3 activity was at normal levels at the time of diagnosis and thereafter depleted over time, indicating an acquired deficiency. For deficient patients, no or very low ficolin-3 protein levels and no lectin pathway-dependent complement activation could be detected. Autoantibodies against ficolin-3 were not detectable. No patients were homozygous for the +1637delC frameshift mutation, whereas in total 10 patients were determined to be heterozygous carriers. These heterozygous patients displayed lower levels of ficolin-3 activity but did not include the deficient patients. Additional possible LoF variants were analyzed but none were enriched in either patients or controls.Conclusions: Contrary to the classical pathway of the complement system we show that genetic ficolin-3 deficiency is not a risk factor for SLE. Instead, acquired ficolin-3 deficiency was observed in a subgroup of SLE patients, possibly due to a potent activation of the lectin pathway that depleted ficolin-3 plasma levels in these individuals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Immunologi
- Immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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