Tasanen-Määttä Kaisa

The breakdown of immunological self-tolerance in a bullous pemphigoid mouse model and in the elderly population

More than skin deep: risk factors and co-morbidities of skin diseases in Finnish population

 

Research Unit: PEDEGO

 

Group leader

Professor Kaisa Tasanen-Määttä (MD, PhD)

 

The breakdown of immunological self-tolerance in a bullous pemphigoid mouse model and in the elderly population

What do we do

Bullous pemphigoid (BP) is the most common blistering skin disease and a prototype of an autoimmune disorder. BP’s symptoms include large blisters and severe pruritus. It is a chronic disease that is associated with heightened mortality rate. The incidence of BP has recently increased recently in several countries in Europe and, in addition, there is an urgent unmet need for novel treatment options for BP to reduce relapses, adverse reactions and the high mortality associated with the current immunosuppressive regimens.

The most important autoantigen in BP is collagen XVII (ColXVII) which is a transmembrane component of hemidesmosomes. Evidence for the pathogenic role of ColXVII autoantibodies comes from clinical findings and experimental BP mouse models, but the factors leading to the initiation of the autoimmunity in the aging skin are poorly understood.

 

Where are we headed

The major aim is to understand better autoimmunization process in BP, and thereby develop better treatment strategies for elderly and fragile BP patients. In our recent mouse model (NC14A) modification of ColXVII induces spontaneously BP-like clinical and pathological findings: Blisters, itching and development of ColXVII-specific IgG and IgA antibodies (Hurskainen et al., 2015). Our hypothesis is that the altered shedding of the ectodomain in NC14A mice creates neoepitopes that break the self-tolerance against ColXVII. We further speculate that in aging human skin, alterations in the ColXVII molecule itself or in the structure of cutaneous basement membrane could trigger the development of autoantibodies. Our recent analyses revealed a molecular level association between BP and neurodegenerative diseases (Kokkonen et al. 2017), which strongly suggests that ColXVII acts as a shared autoantigen in neurodermatological interact. Our specific aims are:

  • To analyze risk factors, co-morbidities and the effects of treatment on morbidity and mortality in BP from a national BP cohort (n=4524) obtained from the Finnish Hospital Discharge Register (FHDR)
  • To analyze autoimmunization against ColXVII in patients with neurodegenerative diseases such Alzheimer’s disease (AD) and multiple sclerosis (MS) and neurological defects in the NC14A mouse model
  • To monitor the immunological mechanism connected to altered ColXVII shedding in the NC14A mouse mode and in BP patients
  • To test therapeutic interventions and predisposing factors using NC14A mice as a preclinical animal model

 

More than skin deep: risk factors and co-morbidities of skin diseases in Finnish population

What do we do

To understand better the life-course determinants and pathways to skin diseases we have performed full dermatologic status investigation of 1932 members of the Northern Finland Birth Cohort 1966 (NFBC 1966). NFBC 1966 is a longitudinal research program which included initially all 12058 children whose expected time of delivery was in the year 1966. The whole NFBC 1966 cohort has been followed on a regular basis since antenatal period by health care records, questionnaires and clinical examinations as well as data on their parents and offspring. During a 46-year follow-up survey, 1932 cohort members were evaluated by multidisciplinary examination including body index, blood pressure, heart echo recording, dental status and several other health measurements.

Another source for epidemiological data is the Finnish Care Register for Health Care (CRHC) which is one of the longest-standing individual-level hospital discharge registries. It contains data from both hospitalized patients and those treated in the outpatient clinic of all hospitals across Finland, but not primary care. CRHC contains personal and hospital identification codes, data on age, gender, length of stay and three subsidiary diagnoses.

In order to clarify the associations between skin diseases and their comorbidities, we have built up two cohorts by using CRHC registry data. First, a cohort of 4300 patients with hidradenitis suppurativa (HS), which is a chronic inflammatory skin disease of hair follicles with abscess formation predominantly involving the inverse areas of the skin. In addition to HS cohort, we have generated another nationwide cohort of over 140000 cases with atopic dermatitis (AD), one of the most common skin diseases in Finland.

 

Where are we headed

  • To analyze the genetic, biological, social or behavioral risk factors of skin diseases in NFBC 1966
  • To analyze risk factors, co-morbidities and the effects of treatment on morbidity in HS and in atopic eczema from  national cohorts obtained from the Finnish Care Register for Health Care

 

Our team

Post doc researchers

  • Docent Laura Huilaja, MD
  • Anna-Kaisa Försti, MD, PhD
  • Nina Kokkonen, PhD
  • Minna Kubin, MD, PhD
  • Suvi-Päivikki Sinikumpu, MD, PhD
  • Jussi Tuusa, PhD

PhD students

  • Karoliina Hulkko, MD
  • Saana Kauppi, MD
  • Outi Lindgren, MD
  • Antti Nätynki, MSc
  • Hannu Tiri MD
  • Outi Varpuluoma MD

Other staff

  • Technician Anja Mattila

 

    Our main collaborators

    Prof. Leena Bruckner-Tuderman, Dept. of Dermatology, Univ. of Freiburg, Germany
    Prof. Enno Schmidt and Prof. Hauke Busch, Dept. of Dermatology, University of Lübeck, Germany
    Prof. Anne Remes, Dept. of Neurology, Univ. of Oulu, Finland
    Prof. Markku Timonen, Juha Auvinen, MD, and Jari Jokelainen, MSc, Inst. of Health Sciences, Univ. of Oulu, Finland
    Docent Miia Turpeinen, Oulu University Hospital, Finland
     

    How to find us

    kaisa.tasanen-maatta[at]oulu.fi

    Last updated: 18.12.2018