Colony-Stimulating Factor-1

Menke, Julia; Amann, Kerstin; Cavagna, Lorenzo; Blettner, Maria; Weinmann, Arndt; Schwarting, Andreas; Kelley, Vicki Rubin

doi:10.1681/asn.2013121356

Cited by 48 publications

(47 citation statements)

References 32 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activated macrophages not seen in healthy kidneys are found in active LN, both in murine models and human disease [12, 14, 15]. Additionally, CSF-1 is a validated biomarker for LN disease activity, in both the serum and urine [9]. Past studies have looked at targeting the CSF-1/CSF-1R signaling pathway in the MRL/lpr model.…”

Section: Discussionmentioning

confidence: 99%

CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus

Chalmers

Wen

Shum

et al. 2017

Clinical Immunology

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that can affect multiple end organs. Kidney and brain are two of the organs most commonly involved in SLE. Past studies have suggested the importance of macrophages in the pathogenesis of lupus nephritis (LN). Furthermore, as the immune effectors of the brain, microglia have been implicated in pathways leading to neuropsychiatric SLE (NPSLE). We depleted macrophages and microglia using GW2580, a small colony stimulating factor-1 receptor (CSF-1R) kinase inhibitor, in MRL-lpr/lpr (MRL/lpr) mice, a classic murine lupus model that displays features of both LN and NPSLE. Treatment was initiated before the onset of disease, and mice were followed for the development of LN and neurobehavioral dysfunction throughout the study. Treatment with GW2580 significantly ameliorated kidney disease, as evidenced by decreased proteinuria, BUN, and improved renal histopathology, despite equivalent levels of IgG and C3 deposition in the kidneys of treated and control mice. We were able to confirm macrophage depletion within the kidney via IBA-1 staining. Furthermore, we observed specific improvement in the depression-like behavioral deficit of MRL/lpr mice with GW2580 treatment. Circulating antibody and autoantibody levels were, however, not affected. These results provide additional support for the role of macrophages as a potentially valuable therapeutic target in SLE. Inhibiting CSF-1 receptor signaling would be more targeted than current immunosuppressive therapies, and may hold promise for the treatment of renal and neuropsychiatric end organ disease manifestations.

show abstract

Section: Discussionmentioning

confidence: 99%

CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus

Chalmers

Wen

Shum

et al. 2017

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Inflammatory molecules expressed by renal tubular epithelia, such as CSF-1, are of clear interest, but their rise may underscore minimal proteinuria and be a part of a general mechanism of tubular cells activation. [40][41][42] Proteinuria is very discriminative between LN and disease controls (SLE, RA, and normal controls) but represents the outcome and cannot be used in positive prediction, for definition, in LN. Therefore, any predictive efforts should be targeted to immunologic biomarkers of lupus activity as we here propose.…”

Section: J Am Soc Nephrol 26: 1905-1924 2015mentioning

confidence: 99%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

Bruschi¹,

Galetti

Sinico

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-a-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including antia-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-a-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine.1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

show abstract

“…The macrophage colony-stimulating factor (M-CSF) is a growth factor that has also been implicated in the pathogenesis of lupus [20,21]. M-CSF supports the proliferation, differentiation and preservation of macrophages and monocytes, including CD14…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus

Masek-Hammerman

Peeva

Ahmad

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary This study's objective was to assess the effects of PD‐0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony‐stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD‐0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre‐ and post‐treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14+ CD16+ monocytes, urinary N‐terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater‐than‐dose‐proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14+ CD16+ cells, uNTX, ALT, AST and CK levels at most time‐points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between‐group differences were seen in CLASI. Patients receiving PD‐0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD‐0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end‐points.

show abstract

Colony-Stimulating Factor-1

Cited by 48 publications

References 32 publications

CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus

CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus

Contact Info

Product

Resources

About