Eculizumab as rescue therapy in severe resistant lupus nephritis: Fig. 1

Pickering, Matthew C.; Ismajli, Mediola; Condon, Marie; McKenna, Nicola; Hall, Angela; Lightstone, Liz; Cook, H. Terence; Cairns, Thomas

doi:10.1093/rheumatology/kev307

Cited by 49 publications

(42 citation statements)

References 8 publications

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“…Furthermore, it has been suggested that eculizumab might be effective in neuromyelitis optica [33], in intractable thrombotic microangiopathy associated with SLE [34] and in severe resistant LN [35]. The results in the present study also suggest the efficacy of eculizumab in the treatment of LN.…”

Section: Discussionsupporting

confidence: 68%

Differential activation mechanisms of serum C5a in lupus nephritis and neuropsychiatric systemic lupus erythematosus

Sakuma

Nagai

Yoshio

et al. 2016

Modern Rheumatology

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Section: Discussionsupporting

confidence: 68%

Differential activation mechanisms of serum C5a in lupus nephritis and neuropsychiatric systemic lupus erythematosus

Sakuma

Nagai

Yoshio

et al. 2016

Modern Rheumatology

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“…Similarly, in both CR and NR, activators of the alternative complement pathway were upregulated in the kidney at flare, while regulators of the alternative complement pathway were down-regulated. As with interferon-inducible transcripts, many of the complement genes tended to normalize expression with treatment in CR, but continued to be abnormally activated or suppressed in NR, suggesting that inhibitors of the alternative complement pathway, such as eculizumab or a C5a receptor antagonist (11, 12), could be effective during the induction phase of LN treatment. Finally, several T cell activation transcripts appeared to be regulated differently in CR and NR kidneys.…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging of the kidney in lupus nephritis to characterize response to treatment

Parikh

Malvar

Song

et al. 2017

Translational Research

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The consequences of treatment for the kidney at the molecular level have not been explored in human lupus nephritis (LN). In this investigation, changes in intra-renal transcript expression were measured and correlated with response in a LN cohort that underwent serial kidney biopsies. The intra-renal transcript expression of 19 patients with proliferative LN (Class III or IV) was measured at diagnostic biopsy (Bx1) and after induction therapy was completed (Bx2) using Nanostring® technology. Patients were segregated by clinical response into complete responders (n=5, CR) or nonresponders (n=4, NR). Transcript expression for each biopsy was compared to normal controls (n=4) and the change in expression was compared in each responder group and between groups. Compared to controls, the CR group had 21 and 28 while NR had 45 and 103 differentially-expressed transcripts at Bx1 and Bx2, respectively. The profiles of these differentially-expressed genes indicated that the type I and II interferon, alternative complement and T cell signaling pathways discriminated CR from NR. Comparing the change in transcript expression from Bx1 to Bx2 revealed a 5-gene signature that differentiated NR from CR and included increased IL1RAP and FCAR in NR and increased NCAM1 in CR. In summary, molecular imaging of serial kidney biopsies from LN patients shows several immune and inflammatory pathways that are dysregulated in the kidneys during active disease that may serve as therapeutic targets to improve clinical response. This approach to LN biomarker development may facilitate personalized medicine in LN and improve long-term kidney outcomes.

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“…[23] More recent evidence also suggested it might be useful in diseases driven by complement activation through the classical pathway, such as antibody-mediated rejection [24] and lupus nephritis. [25,26] In these conditions confirmatory evidence is however awaited and clinical trials are in progress. In our patient, eculizumab efficiently blocked C5b-9 deposition ex vivo, contrarily to plasma exchange, and maintained hematological remission.…”

Section: Discussionmentioning

confidence: 99%