Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study

Dekkema, Gerjan; Abdulahad, Wayel H.; Bijma, Theo; Moran, Sarah; Ryan, Louise; Little, Mark A.; Stegeman, Coen A.; Heeringa, Peter; Sanders, Jan-Stephan

doi:10.1093/ndt/gfy018

Cited by 34 publications

(42 citation statements)

References 31 publications

(46 reference statements)

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“…The acute-phase markers C-reactive protein and erythrocyte sedimentation rate are of limited use in evaluating disease activity due to their lack of specificity. Other disease activity biomarkers, including urinary soluble CD163, are under evaluation for use in assessing disease activity but await validation for routine clinical use [165][166][167] .…”

Section: Biomarkersmentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

571

507

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The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

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Section: Biomarkersmentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

571

507

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“…5). FSP1 levels in U-EVs correlated positively with urinary sCD163 levels, which are already an established biomarker of active renal vasculitis [18,36] and LN [35] ( Fig. 6).…”

Section: Discussionmentioning

confidence: 90%

“…Urinary sCD163 levels were measured using a commercial ELISA kit according to the manufacturer's instructions (DY1607 Duo Set, R&D Systems, Minneapolis, MN, USA) [18,35,36]. Stored urine samples were diluted 1: 4 or 1: 10 as described previously [18].…”

Section: Sandwich Elisa For Urinary Scd163mentioning

confidence: 99%

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

Morikawa

Takahashi

Kamiyama

et al. 2018

Nephron

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Background/Aims: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. Methods: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. Results: Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated with rates of biopsy-proven cellular crescent formation (r = 0.562, p < 0.001) and total crescent formation (r = 0.448, p = 0.005) among total glomeruli; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy (p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed (r = 0.367, p < 0.05). Conclusion: These data suggest that a portion of urinary FSP1 is secreted as EVs originating from podocytes, and that FSP1 levels reflect active and ongoing glomerular injury and disease activity, such as cellular crescent formation.

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“…Abundant M2 macrophage infiltration in PNGD lesions was observed with elevated serum level of sCD163 in the present case, suggesting that M2 macrophages may play a role in this condition. However, serum sCD163 levels in GPA [16,17] have not been defined, and the pathomechanisms for PNGD in GPA and ANCA-related angiitis are still unknown [7,8]. Further study will be necessary to reveal the pathogenesis of PNGD in GPA.…”

Section: Discussionmentioning

confidence: 99%

Palisaded Neutrophilic and Granulomatous Dermatitis in a Patient with Granulomatosis with Polyangiitis

et al. 2020

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KeywordsGranulomatosis with polyangiitis · PR3-ANCA · M2 macrophage · Palisaded neutrophilic and granulomatous dermatitis · CD163 AbstractPalisaded neutrophilic and granulomatous dermatitis (PNGD) shows various clinical features and is histologically characterized by palisaded granulomas surrounding degenerated collagen. PNGD is known to be associated with a variety of systemic conditions such as rheumatoid arthritis and systemic lupus erythematosus. Furthermore, PNGD has been reported to be associated with antineutrophilic cytoplasmic antibody-associated vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis. Here, we report a case of PNGD associated with GPA, which showed the infiltration of CD163-positive M2 macrophages in the skin lesion with elevated serum level of soluble CD163 (sCD163). The serum sCD163 level was reduced to normal range after systemic steroid therapy. Thus, M2 macrophages may play a role in the pathomechanisms of PNGD associated with GPA.

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Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study

Abstract: Measurement of usCD25 and ssCD25 complements usCD163 in the detection of active renal vasculitis.

Cited by 34 publications

References 31 publications

ANCA-associated vasculitis

ANCA-associated vasculitis

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

Palisaded Neutrophilic and Granulomatous Dermatitis in a Patient with Granulomatosis with Polyangiitis

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