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

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

doi:10.1093/ndt/gfy018

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background. Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV.

Methods. sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4(+) T and CD4(+) T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and recursive partitioning was used to calculate whether usCD25 and serumsoluble CD25 (ssCD25) add utility to usCD163.

Results. usCD25, ssCD25 and usCD163 levels were significantly higher during active renal disease and significantly decreased after induction of remission. A combination of usCD25, usCD163 and ssCD25 outperformed all individual markers (sensitivity 84.7%, specificity 95.1%). Patients positive for sCD25 but negative for usCD163 (n = 10) had significantly higher C-reactive protein levels and significantly lower serum creatinine and proteinuria levels compared with the usCD163positive patients. usCD25 correlated positively with urinary CD4(+) T and CD4(+) TEM cell numbers, whereas ssCD25 correlated negatively with circulating CD4(+) T and CD4+ TEMcells.

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

Original language	English
Pages (from-to)	234-242
Number of pages	9
Journal	Nephrology, Dialysis, Transplantation
Volume	34
Issue number	2
DOIs	https://doi.org/10.1093/ndt/gfy018
Publication status	Published - Feb-2019

Keywords

ANCA vasculitis
glomerulonephritis
renal dysfunction
soluble CD25
soluble CD163
T-CELL-ACTIVATION
DISEASE-ACTIVITY
WEGENERS-GRANULOMATOSIS
MARKERS
INTERLEUKIN-2-RECEPTOR
MAINTENANCE
ANTIBODIES
NEPHRITIS

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10.1093/ndt/gfy018

Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort studyFinal publisher's version, 443 KBLicence: Taverne

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Dekkema, G. J., Abdulahad, W. H., Bijma, T., Moran, S. M., Ryan, L., Little, M. A., Stegeman, C. A., Heeringa, P., & Sanders, J.-S. F. (2019). Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrology, Dialysis, Transplantation, 34(2), 234-242. https://doi.org/10.1093/ndt/gfy018

@article{0eac64fe7f784d2193a351e795d0083a,

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

abstract = "Background. Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV.Methods. sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4(+) T and CD4(+) T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and recursive partitioning was used to calculate whether usCD25 and serumsoluble CD25 (ssCD25) add utility to usCD163.Results. usCD25, ssCD25 and usCD163 levels were significantly higher during active renal disease and significantly decreased after induction of remission. A combination of usCD25, usCD163 and ssCD25 outperformed all individual markers (sensitivity 84.7%, specificity 95.1%). Patients positive for sCD25 but negative for usCD163 (n = 10) had significantly higher C-reactive protein levels and significantly lower serum creatinine and proteinuria levels compared with the usCD163positive patients. usCD25 correlated positively with urinary CD4(+) T and CD4(+) TEM cell numbers, whereas ssCD25 correlated negatively with circulating CD4(+) T and CD4+ TEMcells.Conclusion. Measurement of usCD25 and ssCD25 complements usCD163 in the detection of active renal vasculitis.",

keywords = "ANCA vasculitis, glomerulonephritis, renal dysfunction, soluble CD25, soluble CD163, T-CELL-ACTIVATION, DISEASE-ACTIVITY, WEGENERS-GRANULOMATOSIS, MARKERS, INTERLEUKIN-2-RECEPTOR, MAINTENANCE, ANTIBODIES, NEPHRITIS",

author = "Dekkema, {Gerjan J} and Abdulahad, {Wayel H} and Theo Bijma and Moran, {Sarah M} and Louise Ryan and Little, {Mark A} and Stegeman, {Coen A} and Peter Heeringa and Sanders, {Jan-Stephan F}",

year = "2019",

month = feb,

doi = "10.1093/ndt/gfy018",

language = "English",

volume = "34",

pages = "234--242",

journal = "Nephrology, Dialysis, Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "2",

}

Dekkema, GJ, Abdulahad, WH , Bijma, T, Moran, SM, Ryan, L, Little, MA, Stegeman, CA , Heeringa, P & Sanders, J-SF 2019, 'Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study', Nephrology, Dialysis, Transplantation, vol. 34, no. 2, pp. 234-242. https://doi.org/10.1093/ndt/gfy018

Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. / Dekkema, Gerjan J; Abdulahad, Wayel H ; Bijma, Theo et al.
In: Nephrology, Dialysis, Transplantation, Vol. 34, No. 2, 02.2019, p. 234-242.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis

T2 - a cohort study

AU - Dekkema, Gerjan J

AU - Abdulahad, Wayel H

AU - Bijma, Theo

AU - Moran, Sarah M

AU - Ryan, Louise

AU - Little, Mark A

AU - Stegeman, Coen A

AU - Heeringa, Peter

AU - Sanders, Jan-Stephan F

PY - 2019/2

Y1 - 2019/2

N2 - Background. Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV.Methods. sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4(+) T and CD4(+) T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and recursive partitioning was used to calculate whether usCD25 and serumsoluble CD25 (ssCD25) add utility to usCD163.Results. usCD25, ssCD25 and usCD163 levels were significantly higher during active renal disease and significantly decreased after induction of remission. A combination of usCD25, usCD163 and ssCD25 outperformed all individual markers (sensitivity 84.7%, specificity 95.1%). Patients positive for sCD25 but negative for usCD163 (n = 10) had significantly higher C-reactive protein levels and significantly lower serum creatinine and proteinuria levels compared with the usCD163positive patients. usCD25 correlated positively with urinary CD4(+) T and CD4(+) TEM cell numbers, whereas ssCD25 correlated negatively with circulating CD4(+) T and CD4+ TEMcells.Conclusion. Measurement of usCD25 and ssCD25 complements usCD163 in the detection of active renal vasculitis.

AB - Background. Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV.Methods. sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4(+) T and CD4(+) T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and recursive partitioning was used to calculate whether usCD25 and serumsoluble CD25 (ssCD25) add utility to usCD163.Results. usCD25, ssCD25 and usCD163 levels were significantly higher during active renal disease and significantly decreased after induction of remission. A combination of usCD25, usCD163 and ssCD25 outperformed all individual markers (sensitivity 84.7%, specificity 95.1%). Patients positive for sCD25 but negative for usCD163 (n = 10) had significantly higher C-reactive protein levels and significantly lower serum creatinine and proteinuria levels compared with the usCD163positive patients. usCD25 correlated positively with urinary CD4(+) T and CD4(+) TEM cell numbers, whereas ssCD25 correlated negatively with circulating CD4(+) T and CD4+ TEMcells.Conclusion. Measurement of usCD25 and ssCD25 complements usCD163 in the detection of active renal vasculitis.

KW - ANCA vasculitis

KW - glomerulonephritis

KW - renal dysfunction

KW - soluble CD25

KW - soluble CD163

KW - T-CELL-ACTIVATION

KW - DISEASE-ACTIVITY

KW - WEGENERS-GRANULOMATOSIS

KW - MARKERS

KW - INTERLEUKIN-2-RECEPTOR

KW - MAINTENANCE

KW - ANTIBODIES

KW - NEPHRITIS

U2 - 10.1093/ndt/gfy018

DO - 10.1093/ndt/gfy018

M3 - Article

C2 - 29506265

SN - 0931-0509

VL - 34

SP - 234

EP - 242

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

IS - 2

ER -

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

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