Ingiäld Hafström group

The research is focused on inflammatory rheumatic diseases, especially rheumatoid arthritis and systemic lupus erythematosus. The group conducts longitudinal and cross-sectional studies of patients with rheumatoid arthritis and systemic lupus erythematosus to predict and understand disease outcome.

About our research

The research is focused on inflammatory rheumatic diseases, especially rheumatoid arthritis and systemic lupus erythematosus. Our main focus is on humans but we also conduct in vitro studies to investigate the mechanism behind these diseases. We take advantage of the large patient groups that we follow over time in our clinic and in national collaboration.

The research focuses on molecular pathogenesis, therapy and outcomes, particularly the associations between abnormal body composition, increased frequency of atherosclerosis and joint destruction. The hope is that increased understanding of why these manifestations occur will enable us to develop "secondary" prevention against these serious co-morbidities.

Keywords:

Rheumatology, body fat mass, bone mineral density, radiological scoring, antibodies against phospholipids, vulnerable plaque, cardiovascular events

Group leader

Ingiäld Hafström

Group Leader, Professor, Senior physician
H7 Department of Medicine, Huddinge

Group members

Sofia Ajeganova

Affiliated to research
H7 Department of Medicine, Huddinge

Margareta Wörnert

Research nurse

Projects

1. Rheumatoid arthritis (RA) - body composition, atherosclerosis and joint destruction. Pathogenesis, predictive factors and impact of therapy

Patients with RA have an increased frequency of obesity and cardiovascular diseases (CVD), and these manifestations seem to be related to a more aggressive disease as to joint destruction, but not always. Factors suggested to be of importance are inflammatory activity, adipokines (a family of signaling molecules regulating carbohydrate and lipid metabolism and mediating obesity, diabetes mellitus, atherosclerosis), lipid metabolism, the diet and the possibility for the individuals to adapt their immune system. If treatment with glucocorticoids has any importance for developing these comorbidities is unknown.

Overall aim of the project

To elucidate the causes of and the molecular mechanisms leading to increase in body fat, cardiovascular disease and destruction of bone and cartilage in RA. Furthermore we try to find factors early in disease that can predict the aforementioned manifestations. Lastly we will study the role of glucocorticoid and biological treatment.

Work plan and methods

Epidemiological, clinical, immunological and molecular studies with participating patients from several large well-characterized RA cohorts, some followed regularly since disease onset. The number of participating patients is large enough to allow for gender specific analyses. A unique part of the project is the combination of clinical and molecular research with nursing aspects of care.

Expected impact of results

An increased knowledge of predictors and mechanisms for the disease manifestations such as obesity, CVD and their relationship to joint destruction and glucocorticoid treatment will have impact on the treatment of the RA patients and hence decrease morbidity and mortality.

2. Understanding the development of atherosclerosis in Systemic lupus erythematosus (SLE)

In systemic lupus erythematosus (SLE), the risk of cardiovascular disease (CVD) is high. This is an important clinical problem but could also shed light on associations between immune reactions and atherosclerosis/CVD.

Overall aim

To study novel immunological protection factors as antibodies against phospholipids (anti-PC) and antibodies against oxidized phospholipids in SLE in relation to atherosclerosis and CVD in SLE.

Work plan and methods

A cohort of SLE patients at Karolinska University Hospital, Huddinge has been carefully investigated from clinical, routine laboratory and more experimental point of view. In addition to inter-media thickness (IMT) -measurements, we also study endothelial function, body composition and measurements of osteoporosis, as well as detailed analysis of dietary habits and biopsy of subcutaneous fat for analysis of fatty acids. In parallel, anti-PC and Annexin A5 related factors will be studied.

Expected impact of results

Enhanced knowledge of causes of CVD in SLE is needed to improve prevention and treatment but may also shed light on the role of immune reactions and autoimmunity in human atherosclerosis and CVD in general.

Research support

  • The Swedish Rheumatism Association
  • King Gustav V 80 year´s Foundation
  • The Swedish Research Council and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet
  • The EU project CVDIMMUNE
  • The CiDAT, -consortium

Selected publications

  1. Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events.
    Ajeganova S, Andersson MLE, Frostegård J, Hafström I. Arthritis Res Ther 2021 07;23(1):201
     
  2. Effects of Atorvastatin on T-Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C-Reactive Protein and Interleukin 6.
    Sun J, Kumar Panda P, Kumar Samal S, Ahuja R, Ajeganova S, Hafström I, Liu A, Frostegård J. ACR Open Rheumatol 2021 Sep;3(9):642-653
     
  3. Reported disability in relation to observed activity limitation, grip strength and physical function in women and men with rheumatoid arthritis.
    Bala SV, Andersson MLE, Forslind K, Svensson B, Hafström I, BMC Rheumatol 2021 May;5(1):1
     
  4. Patients with SLE have higher risk of cardiovascular events and mortality in comparison with controls with the same levels of traditional risk factors and intima-media measures, which is related to accumulated disease damage and antiphospholipid syndrome: a case-control study over 10 years.
    Ajeganova S, Hafström I, Frostegård J, Lupus Sci Med 2021 02;8(1):
     
  5. Team Rehabilitation in Inflammatory Arthritis Benefits Functional Outcomes Along With Improved Body Composition Associated With Improved Cardiorespiratory Fitness.
    Ajeganova S, Wörnert M, Hafström I, J Rheumatol 2021 Sep;48(9):1371-1378
     
  6. Low levels of PCSK9 are associated with remission in patients with rheumatoid arthritis treated with anti-TNF-α: potential underlying mechanisms.
    Frostegård J, Ahmed S, Hafström I, Ajeganova S, Rahman M, Arthritis Res Ther 2021 01;23(1):32
     
  7. A Swedish register-based, long-term inception cohort study of patients with rheumatoid arthritis - results of clinical relevance.
    Hafström I, Ajeganova S, Andersson ML, Bala SV, Bergman S, Bremander A, Forslind K, Malm K, Svensson B, Open Access Rheumatol 2019 ;11():207-217
     
  8. Anti-citrullinated protein antibodies are associated with osteopenia but not with pain at diagnosis of rheumatoid arthritis: data from the BARFOT cohort.
    Hafström I, Ajeganova S, Forslind K, Svensson B, Arthritis Res Ther 2019 02;21(1):45
     
  9. The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor.
    Ajeganova S, van Steenbergen HW, Verheul MK, Forslind K, Hafström I, Toes RE, Huizinga TW, Svensson B, Trouw LA, van der Helm-van Mil AH, Ann Rheum Dis 2017 Jan;76(1):112-118
     
  10. Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.
    Derksen VF, Ajeganova S, Trouw LA, van der Helm-van Mil AH, Hafström I, Huizinga TW, Toes RE, Svensson B, van der Woude D, Ann Rheum Dis 2017 04;76(4):716-720