P13 Acquired ficolin-3 deficiency in patients with systemic lupus erythematosus

• Published in: Lupus science & medicine Vol. 11; no. Suppl 1; pp. A51 - A52
• Main Authors: Lindelöf, Linnea, Rantapää-Dahlqvist, Solbritt, Lundtoft, Christian, Sandling, Johanna K, Leonard, Dag, Sayadi, Ahmed, Rönnblom, Lars, Enocsson, Helena, Sjöwall, Christopher, Jönsen, Andreas, Bengtsson, Anders A, Hong, Mun-Gwan, Diaz-Gallo, Lina-Marcela, Bianchi, Matteo, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Ekdahl, Kristina Nilsson, Nilsson, Bo, Gunnarsson, Iva, Svenungsson, Elisabet, Eriksson, Oskar
• Format: Journal Article
• Language: English
• Published: London Lupus Foundation of America 14.03.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Lectins; Lupus; Mutation; Poster Presentations
• ISSN: 2053-8790
• DOI: 10.1136/lupus-2024-el.67

ObjectiveFicolin-3 is the main initiator of the lectin pathway of complement 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.MethodsSerum samples from SLE patients (n=786) and matched controls (n=566) were collected from the Karolinska Institute and Umeå University Hospital. The ficolin-3 activity was 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 rs532781899 and other potential loss-of-function (LoF) variants.ResultsThis screening revealed that the ficolin-3 activity varies largely in patients with SLE. The activity levels also show that SLE patients have elevated ficolin-3 activity compared to the control group (p<0.0001). Four SLE patients were determined to be ficolin-3 deficient. For two of these patients, the ficolin-3 activity fluctuated over time, where one even had normal levels at the time of diagnosis with a subsequent depletion 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 only detected in serum from one of the deficient patients. No patients were homozygous for the frame-shift mutation rs532781899, whereas 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.ConclusionsContrary to the classical pathway of the complement system, we show no evidence for an association between genetic ficolin-3 deficiency and SLE susceptibility. 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 serum levels in these individuals.