The complement system as a potential therapeutic target in rheumatic disease

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The complement system as a potential therapeutic target in rheumatic disease. / Trouw, Leendert A.; Pickering, Matthew C.; Blom, Anna M.

I: Nature Reviews Rheumatology, Vol. 13, Nr. 9, 01.09.2017, s. 538-547.

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Trouw, Leendert A. ; Pickering, Matthew C. ; Blom, Anna M. / The complement system as a potential therapeutic target in rheumatic disease. I: Nature Reviews Rheumatology. 2017 ; Vol. 13, Nr. 9. s. 538-547.

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TY - JOUR

T1 - The complement system as a potential therapeutic target in rheumatic disease

AU - Trouw, Leendert A.

AU - Pickering, Matthew C.

AU - Blom, Anna M.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated.

AB - Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated.

KW - rheumatic disease

KW - complement system

KW - therapeutic target

UR - http://www.scopus.com/inward/record.url?scp=85028014367&partnerID=8YFLogxK

U2 - 10.1038/nrrheum.2017.125

DO - 10.1038/nrrheum.2017.125

M3 - Review article

VL - 13

SP - 538

EP - 547

JO - Nature Reviews Rheumatology

JF - Nature Reviews Rheumatology

SN - 1759-4804

IS - 9

ER -