Updates on the Treatment of Lupus Nephritis

Bomback, Andrew S.; Appel, Gerald B.

doi:10.1681/asn.2010050472

Cited by 156 publications

(146 citation statements)

References 66 publications

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“…Severe SLE disease or patients that have signs of renal involvement require more aggressive drugs including mycophenolate mofetil, azathioprine, and/or cyclophosphamide (CTX) (18). Immunosuppressive drugs such as CTX, azathioprine, and mycophenolate mofetil are very toxic, and only 50% of treated patients enter complete remission, with relapse rates up to 30% over a 2-y period (19).…”

mentioning

confidence: 99%

Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2

Lu¹,

Stump²,

Wallace³

et al. 2011

The Journal of Immunology

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Accumulating evidence suggests that autoreactive plasma cells play an important role in systemic lupus erythematosus (SLE). In addition, several proinflammatory cytokines promote autoreactive B cell maturation and autoantibody production. Hence, therapeutic targeting of such cytokine pathways using a selective JAK2 inhibitor, CEP-33779 (JAK2 enzyme IC50 = 1.3 nM; JAK3 enzyme IC50/JAK2 enzyme IC50 = 65-fold), was tested in two mouse models of SLE. Age-matched, MRL/lpr or BWF1 mice with established SLE or lupus nephritis, respectively, were treated orally with CEP-33779 at 30 mg/kg (MRL/lpr), 55 mg/kg or 100 mg/kg (MRL/lpr and BWF1). Studies included reference standard, dexamethasone (1.5 mg/kg; MRL/lpr), and cyclophosphamide (50 mg/kg; MRL/lpr and BWF1). Treatment with CEP-33779 extended survival and reduced splenomegaly/lymphomegaly. Several serum cytokines were significantly decreased upon treatment including IL-12, IL-17A, IFN-α, IL-1β, and TNF-α. Anti-nuclear Abs and frequencies of autoantigen-specific, Ab-secreting cells declined upon CEP-33779 treatment. Increased serum complement levels were associated with reduced renal JAK2 activity, histopathology, and spleen CD138+ plasma cells. The selective JAK2 inhibitor CEP-33779 was able to mitigate several immune parameters associated with SLE advancement, including the protection and treatment of mice with lupus nephritis. These data support the possibility of using potent, orally active, small-molecule inhibitors of JAK2 to treat the debilitative disease SLE.

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confidence: 99%

Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2

Lu¹,

Stump²,

Wallace³

et al. 2011

The Journal of Immunology

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“…Eventhough a firm conclusion cannot be drawn at this level, the outcome does not appear to be favourable. The prognosis of these patients are worse or atleast as bad as those patients with nephritis who meet the criteria for SLE (18) . Kim et al reported a similar case of nephritis with persistent absence of autoantibodies in serum .…”

Section: Discussionmentioning

confidence: 99%

Non Lupus Full House Nephropathy – A Clinical and Pathological Correlation Study

S¹,

Samuel²,

Arun³

et al. 2017

IOSR JDMS

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“…LN and NPSLE are two of the most severe manifestations of lupus 3, 12– 14 . Consequently, patients who present with NPSLE or LN are frequently treated with potent immunosuppressive agents, and immunosuppression is usually continued for prolonged periods 15, 16 .…”

Section: The Unpredictable Course Of Slementioning

confidence: 99%

Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus

Thurman

Serkova

2015

F1000Res

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Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system (CNS). Conventional radiological examinations in SLE patients include volumetric/ anatomical computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). The utility of these modalities is limited, however, due to the complexity of the disease. Furthermore, CT and MRI contrast agents are contraindicated in patients with renal impairment. Various radiologic methods are currently being developed to improve disease characterization in patients with SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols have been developed to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine imaging) have also been developed for diagnosing SLE with high sensitivity, and for monitoring disease activity. This paper reviews the challenges in evaluating disease activity in patients with LN and neuropsychiatric systemic lupus erythematosus (NPSLE). We describe novel MRI and positron-emission tomography (PET) molecular imaging protocols using targeted iron oxide nanoparticles and radioactive ligands, respectively, for detection of SLE-associated inflammation.

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Updates on the Treatment of Lupus Nephritis

Cited by 156 publications

References 66 publications

Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2

Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2

Non Lupus Full House Nephropathy – A Clinical and Pathological Correlation Study

Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus

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