Selected articles August 2016

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On antiphospholipid antibodies in patients with systemic lupus erythematous

 

Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus (pages 95–99)

L. Garabet, I.-M. Gilboe, M.-C. Mowinckel, A. F. Jacobsen, T. E. Mollnes, P. M. Sandset and E.-M. Jacobsen

 

Here, researchers from Norway show that systemic lupus erythematous (SLE)

patients with antiphospholipid (aPL) have significantly lower levels of complement C3 and C4 compared to SLE patients without aPL.

 

SLE is an autoimmune disease characterized by multiorgan involvement, presence of immune complexes in the affected organs and the excessive production of a variety of autoantibodies, including aPL antibodies. Activation of the complement system and low complement levels are common in SLE.

 

This study aimed to investigate the association between aPL and complement levels in patients with SLE.

 

Lamya Garabet is the first author of the paper:

 

 – My main responsibility was, together with my supervisors, to plan the study, to do the required preparations as the ethical and data permission requirements before starting the study, acquiring the blood samples and the clinical information from the registry, putting the test results together and to do the statistical analysis together with my main supervisor Dr. Eva Jacobsen. Then I wrote the article, did the changes suggested by my co-authors and did the submission. The blood tests were analyzed by a study bioengineer who is a co-author; Marie-Christine Mowinckel.

  

– Our main findings are that SLE patients with aPL antibodies have significantly lower levels of complement C3 and C4 than SLE patients without aPL, and that there was no significant difference in CRP between aPL-positive and aPL-negative SLE patients. Our findings suggest that lower C3 and C4 values in aPL-positive SLE patients may reflect a higher consumption of C3 and C4 due to higher complement activation probably indicating that these antibodies cause complement-activation. Another possible explanation is that this subgroup of SLE patients has a higher disease activity and thus higher complement activation, Lamya Garabet concludes.

  

  

 

Association between type I IFN signature and a subgroup of myositis patients

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies (pages 100–109)

L. Ekholm, S. Vosslamber, A. Tjärnlund, T. D. de Jong, Z. Betteridge, N. McHugh, L. Plestilova, M. Klein, L. Padyukov, A. E. Voskuyl, I. E. M. Bultink, D. Michiel Pegtel, C. P. Mavragani, M. K. Crow, J. Vencovsky, I. E. Lundberg and C. L. Verweij

 

In this study, Swedish, Dutch and Czech researchers reveal an association between the type I IFN signature and a subgroup of myositis patients with autoantibodies against RNA-binding proteins.

 

Myositis is a heterogeneous group of autoimmune diseases characterized by proximal muscle weakness and muscle inflammation, and can be subgrouped into polymyositis, dermatomyositis and inclusion body myositis.  A common feature is the presence of autoantibodies.

 

The aim of the study was to test the hypothesis that autoantibodies directed against RNA-binding proteins in patients with myositis are associates with a type I IFN signature and thus potentially could induce IFN production.

 

Louise Ekholm, the first author of the paper is a PhD student at the Karolinska Institutet in the myositis group of professor Ingrid Lundberg.

 

– I will include this study in my thesis, which is defended on December 16 this year, she explains.

 

She has coordinated the work in this study, collected the clinical information on the myositis cohort as well as written the actual paper in collaboration with her co-authors.

 

– Otherwise, this project was collaboration between researchers here at the Karolinska Institutet, in the Netherlands and in the Czech Republic.

 

– Our study confirms that there are several different pathogenic mechanisms in the different sub groups of myositis. We have found that the IFN system is activated in patients with autoantibody mono-specific against RNA-binding proteins and in patients with multispecific antibody status, meaning that they have two ore more types of antibodies per individual.

 

The researchers also found that IFN alpha is mainly responsible for the IFN signature.

 

Taken together, the results from this study emphasize the need for careful molecular phenotyping of patients to gain better understanding of molecular pathogenesis and to improve treatment for myositis patients.