Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Pepper, Ruth J.; Draibe, Juliana; Caplin, Ben; Fervenza, Fernando C.; Hoffman, Gary S.; Kallenberg, Cees G. M.; Langford, Carol A.; Monach, Paul A.; Seo, Philip; Spiera, Robert; Clair, E. William St.; Tchao, Nadia K.; Stone, John H.; Specks, Ulrich; Merkel, Peter A.; Salama, Alan D.

doi:10.1002/art.39814

Cited by 50 publications

(33 citation statements)

References 36 publications

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“…38 Another was changes in serum calprotectin levels, which increased while on therapy between baseline and month 3 or 6, in samples from the RAVE trial, again only in those treated with rituximab (like the predictive ability of proteinase-3-ANCA). 39 This suggests that differences exist in suppression of various inflammatory pathways when using different induction regimens, despite similar clinical remission rates, highlighting again that clinical remission is not telling us everything about underlying disease pathway suppression. Perhaps unsurprisingly, since the change in calprotectin was not predictive of relapse in cyclophosphamide-treated patients from RAVE, no association with relapse was found using samples from the MYCYC (mycophenolate vs cyclophosphamide) trial (unpublished data).…”

Section: Subclinical Inflammation and Predicting Relapsesmentioning

confidence: 99%

Relapse in Anti-Neutrophil Cytoplasm Antibody (ANCA)–Associated Vasculitis

Salama

2020

Kidney International Reports

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Clinical relapses are common in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis, necessitating repeated treatment with immunosuppressive therapy, and increasing the risks of severe adverse events. Better understanding the basis of relapse would help stratify patients, testing the notion that more treatment may prevent development of relapse, whereas in those at low risk of disease flares, treatment minimization may be appropriate, reducing risks of adverse events, most notably infectious complications and drug toxicity. However, relapse can only occur following remission, and although defining clinical remission may seem straightforward, there is evidence in many remission patients of persistent inflammatory and immunological activity, at levels above those found in healthy individuals. This suggests that we may not truly be achieving disease remission in many patients and these persistent responses may set the patient up for subsequent disease flares. Understanding the underlying pathophysiological basis of disease activity and remission is paramount to help define better biomarkers of relapse, which should positively affect adverse events and patient outcomes.

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Section: Subclinical Inflammation and Predicting Relapsesmentioning

confidence: 99%

Relapse in Anti-Neutrophil Cytoplasm Antibody (ANCA)–Associated Vasculitis

Salama

2020

Kidney International Reports

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“…Serum calprotectin is elevated in patients in the acute phase of AAV compared to patients in remission, but during remission the normal levels are not reached[ 12 ]. As shown in a recent study, an increase in serum calprotectin by month 2 or 6 compared to diagnostic time in rituximab treated patients was an independent risk factor for relapse of the disease in PR3 AAV[ 13 ]. Serum calprotectin has shown its utility as a marker of activity and relapse in other autoimmune diseases[ 14 ].On the other hand, the usefulness as biomarker of urine calprotectin AAV has not been well evaluated although it has been proven as an indicator of parenchymatous acute renal failure when inflammation is present[ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Calprotectin as a smoldering activity detection tool and renal prognosis biomarker in ANCA associated vasculitis

et al. 2018

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BackgroundCalprotectin is produced by neutrophils and macrophages, and released during the acute phase of the ANCA vasculitis. The aim of our study was to determine if serum and urine calprotectin are disease activity and prognosis biomarkers in ANCA vasculitis patients during remission.MethodsForty-two ANCA vasculitis patients were included. Twenty-seven patients were in remission phase under immunosuppressive therapy, and 15 patients were in the acute phase. Four healthy controls were included. We determined calprotectin in serum and urine samples at the time of the inclusion. We recorded the incidence of relapse and the evolution of GFR, proteinuria, hematuria, and C reactive protein and ANCA titer during 24 months of follow-up.ResultsIn remission phase, serum calprotectin was higher than in healthy controls but lower compared to acute patients (p = 0.05). Serum calprotectin at inclusion was higher in patients who increased proteinuria during follow-up (p = 0.04), with hematuria (p = 0.08), and with non-decreasing ANCA titer (p = 0.0019). Serum calprotectin at inclusion in stable patients who subsequently decreased GFR during follow-up was higher compared with those with a stable or improving GFR (p = 0.03). Urine calprotectin was lower in patients with sclerotic histology in remission (p = 0.03) and acute phase (p = 0.12) compared to the rest of histologies.ConclusionsWorsening of renal function, hematuria, rising proteinuria and non-decreasing ANCA correlated with higher levels of serum calprotectin at recruitment. Low urine calprotectin was found in patients with sclerotic histology. Calprotectin during remission in ANCA vasculitis may be useful to identify subclinical inflammation and worse renal prognosis patients.

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“…Despite this, even in remission, proteomic results from GPA neutrophils do not fully resemble HC, indicating that treatment could not overcome all intrinsic defects likely to contribute to the pathogenesis of this disease. Interestingly, our proteomics analysis of neutrophil cytosols under basal conditions has identified S100A8/A9, which constitutes 40% of cytosolic proteins, a disease biomarker recently identified in GPA, 20,31 demonstrating that examining dysregulated cytosolic proteins could represent a valid tool for biomarker discovery. Notably, S100A8/9 proteins complexes that are stabilized and secreted during apoptosis can promote neutrophil survival, thus potentially delaying the resolution of inflammation.…”

Section: Discussionmentioning

confidence: 89%