Oskar Eriksson's projects on the complement system

Molecular mechanisms of lectin pathway initiation in humans

We are using a range of experimental systems to define how the lectin pathway is activated and regulated in humans.

While MBL binds strongly to mannose-rich microbial sugars, ficolin-3 seems to display a preference for post-translationally modified proteins. In particular, ficolin-3 binds strongly to proteins derivatized by acetylation, and we are using a systematic approach to evaluate the capacity of immunogenic post-translationally modified proteins to activate complement through the lectin pathway.

In related protect, we have used proteome-wide protein arrays covering > 20 000 full-length human proteins to investigate the lectin pathway interactome, in order to identify regulators and modulators of complement activation. Hits will be further explored and validated using biochemical means, and functional cell-based systems and ex vivo whole blood models.

Development of novel assays to asses and quantify lectin pathway function

An important aim of our research is to develop and refine experimental and clinical complement diagnostics, and we work in close proximity to the clinical complement diagnostics lab at Uppsala University Hospital. We have developed assays to quantify lectin pathway function in clinical samples, where recent projects include analysis of plasma or serum samples from patients with Covid-19 and the autoimmune disorder systemic lupus erythematosus (SLE).

Genetic determinants of lectin pathway function

A recurring observation from our patient studies is an extensive variation in lectin pathway between individuals, in line with the general pattern of large variation in immune-related pathways in most populations. We are interested in the genetic contribution to this phenomenon, and recent studies in the group have explored genetic variation in lectin pathway genes and how these are related to clinical phenotypes in disorders with systemic inflammation. Through collaborations with Swedish research networks and consortia, we are exploring the genetic contribution to lectin pathway function in e.g. Covid-19 and SLE.