Ytterberg’s group

The Ytterberg minigroup

Jimmy Ytterberg, PhD

Susanna Lundström, PhD

Ernesto Gonzalez de Valdivia, PhD

Nataliya Tarasova, PhD student

The Zubarev lab is part of the PRIMI (PRedIctive Models in Inflammatory diseases), an initiative funded by the Swedish Foundation for Strategic Research (SSF). The goal of the initiative is to find biomarkers in chronic inflammation and the working hypothesis is that several chronic inflammatory diseases originate in the lung and at a later stage affect other tissues. The three main diseases in this initiative are rheumatoid arthritis (RA), sarcoidosis and myositis. The three diseases are autoimmune diseases, which affect different tissues: RA affects joints, sarcoidosis affects lungs, and myositis affects muscles. Of the three, only in RA is the antigen known. The initiative is headed by Prof. Lars Klareskog, the director of the Center of Molecular Medicine at KI and head of the department of Rheumatology. The other main PIs are Prof. Roman Zubarev (mass spectrometry), Prof. Rikard Holmdahl (animal models), Prof. Johan Grunewald (sarcoidosis), and Prof. Ingrid Lundgren (myositis).

Dr. Ytterberg is responsible for the mass spectrometry analysis of the samples generated by the consortia and work closely together with Dr. Rutishauser, the core facility manager of PK/KI at MBB.

Currently, the main PRIMI projects are:

  • Identification of citrullinated proteins in biopsies from RA patients using shotgun proteomics.
  • Characterization of glycosylation patterns of antibodies
  • Peptide elution from MHC class II

Identification of citrullinated proteins in biopsies from RA patients using shotgun proteomics.

Anti-citrullinated peptide/protein antibodies (ACPA) are currently one of the best biomarkers for RA, and are normally detected by a cyclic citrullinated peptide (CCP) kit. The identities of some of these proteins are known,  but more must exist. The project aims to increase the numbers of potential targets and identify citrullinated proteins from biopsies from patients with RA in an unbiased manner using shotgun proteomics.  Together with Ms Tarasova and Dr. Haraldsson at LCBKI, Dr. Ytterberg is also developing affinity methods for the enrichment of citrullinated peptides.

Characterization of glycosylation patterns of antibodies

An increasingly important parameter in diagnosing IgG functionality including Fc and complement activation is by studying the N-linked Fc IgG glycosylation pattern. It has recently been shown that pro-inflammatory or anti-inflammatory effector functions of IgG are correlating with differences in these patterns. Thus, to better understand the role of ACPAs we are determining the glyosylation pattern of ACPAs, polyclonal antibodies and biologically well-defined monoclonal antibodies. The characterization effort is headed by Dr. Lundström in collaboration with Holmdahl and Klareskog labs.

Peptide elution from MHC class II complexes

Antigen-derived peptides presented by MHC class II comp on the surface of antigen presenting cells (APC) activate T-helper cells, which can then trigger the adaptive immune system. The antigen-derived peptides are generated by phagocytosis of cells, cell debris or abnormal proteins, and represent indicate what cells and/or proteins the APC has been exposed to. These peptides can also be candidates in vaccination trials. Identification of these peptides could potentially be a tool to identify what antigen has triggered an immune response in patients. Together with Tina Heyder from the Grunewald group, we are developing methods for isolation of MHC class II peptides from small number of cells.

Proteomics-bases monocyte assay to determine immunogenicity

In collaboration with Profs Lundberg and Harris, we are developing a proteomics-bases monocyte assay to determine immunogenicity. The aims are to first develop and an assay that can score anti- and pro-inflammatory responses and then use the assay to estimate the immunogenicity of protein, peptides, and/or antibodies. The long term goal is to use the assay to predict response to treatment for patients affected in immunological diseases. The effort to set up the monocyte cell cultures in the Zubarev lab is headed by Dr.  Gonzalez and Ms Tarasova.