Ingiäld Hafström group

Longitudinal and cross-sectional studies of patients with rheumatoid arthritis and systemic lupus erythematosus to predict and understand disease outcome.

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, diet, body fat mass, bone mineral density, radiological scoring, antibodies against phospholipids, vulnerable plaque


Ingiäld Hafström, Group Leader, Professor, Senior physician
Johan Frostegård, Professor, Senior physician
Ann-Charlotte Elkan, RN, PhD, Research nurse
Sofia Ajeganova, MD, PhD, Senior physician
Eva Waldheim, RN, PhD, Research nurse  
Margareta Wörnert, RN, Research nurse


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

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.

Financial 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

Effect of biological therapy on levels of atheroprotective antibodies against phosphorylcholine and apolipoproteins in rheumatoid arthritis - a one year study.
Ajeganova S, Fiskesund R, de Faire U, Hafström I, Frostegård J
Clin. Exp. Rheumatol. ;29(6):942-50

Late-onset neutropenia following rituximab therapy in rheumatic diseases: association with B lymphocyte depletion and infections.
Tesfa D, Ajeganova S, Hägglund H, Sander B, Fadeel B, Hafström I, et al
Arthritis Rheum. 2011 Aug;63(8):2209-14

Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine are independently associated with carotid artery atherosclerosis 5 years after rheumatoid arthritis onset--a prospective cohort study.
Ajeganova S, Ehrnfelt C, Alizadeh R, Rohani M, Jogestrand T, Hafström I, et al
Rheumatology (Oxford) 2011 Oct;50(10):1785-93

Effects on joint destruction and remission, bone turnover and lack of influence on atherogenesis: a review of the BARFOT low-dose prednisolone studies on patients with early RA.
Svensson B, Hafström I
Clin. Exp. Rheumatol. ;29(5 Suppl 68):S63-7

Cardiovascular co-morbidity in patients with rheumatic diseases.
Frostegård J
Arthritis Res. Ther. 2011 Jun;13(3):225

Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass--a cross sectional study.
Elkan A, Håkansson N, Frostegård J, Hafström I
BMC Musculoskelet Disord 2011 Jan;12():13

Treatment with low-dose prednisolone is associated with altered body composition but no difference in bone mineral density in rheumatoid arthritis patients: a controlled cross-sectional study.
Engvall I, Brismar K, Hafström I, Tengstrand B
Scand. J. Rheumatol. 2011 May;40(3):161-8

Joint destruction in early rheumatoid arthritis over 8 years is similar in women and men despite apparently higher disease activity and poorer function in women.
Hafström I, Bala V, Albertsson K, Forslind K, Svensson B,
Ann. Rheum. Dis. 2011 Apr;70(4):709-10

Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus.
Anania C, Gustafsson T, Hua X, Su J, Vikström M, de Faire U, et al
Arthritis Res. Ther. 2010 ;12(6):R214

Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months.
Engvall I, Tengstrand B, Brismar K, Hafström I
Arthritis Res. Ther. 2010 ;12(5):R197

Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage.
Ahlmén M, Svensson B, Albertsson K, Forslind K, Hafström I,
Ann. Rheum. Dis. 2010 Jan;69(1):230-3

Increased expression of proto-oncogene survivin predicts Joint destruction and persistent disease activity in early rheumatoid arthritis.
Svensson B, Hafström I, Forslind K, Albertsson K, Tarkowski A, Bokarewa M
Ann. Med. 2010 ;42(1):45-54

Anti-apoA-1 IgG and oxidized LDL are raised in rheumatoid arthritis (RA): potential associations with cardiovascular disease and RA disease activity.
Vuilleumier N, Bratt J, Alizadeh R, Jogestrand T, Hafström I, Frostegård J
Scand. J. Rheumatol. 2010 Nov;39(6):447-53