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sIL7R concentrations in the serum reflect disease activity in the lupus kidney.

Lauwerys BR, Husson SN, Maudoux AL, Badot V, Houssiau FA - Lupus Sci Med (2014)

Bottom Line: These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio.Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations.Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE.

View Article: PubMed Central - PubMed

Affiliation: Pôle de pathologies rhumatismales , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium ; Service de Rhumatologie , Cliniques Universitaires Saint-Luc , Brussels , Belgium.

ABSTRACT

Objectives: Evaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study, we reported that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly associated with nephritis in SLE patients. In the present study, we wanted to confirm the association between changes in serum sIL7R concentrations and renal disease activity in a large longitudinal cohort of SLE nephritis patients.

Methods: Sera were harvested longitudinally in 105 SLE nephritis patients. Serum sIL7R cut-off value for the detection of SLE nephritis activity was determined as the mean sIL7R concentration in non-nephritis SLE patients + 2 SDs using data collected in our previous study. Patients with glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (n=17) were excluded from the study due to persistently elevated serum sIL7R values.

Results: Serum sIL7R concentrations above the renal cut-off value were observed in 25 (out of 88) patients with a normal GFR. These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a renal British Isles Lupus Assessment Group index (BILAG) A within the next 3 months, while this was only the case in four out of the 63 other patients (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the detection of a renal BILAG A. Combination of serum sIL7R with any of the classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an increased specificity for the detection of a renal flare. Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations.

Conclusions: Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of an SLE nephritis flare.

No MeSH data available.


Related in: MedlinePlus

Receiving operator characteristic (ROC) curves displaying the performances of serum soluble form of the interleukin-7 receptor (sIL7R) (A), serum anti-double-stranded DNA antibodies (B), serum C3 (C) and urinary protein to creatine (UPC) (D) measurements for the detection of a renal BILAG A in a cohort of SLE nephritis patients. The left panels show the variations in sensitivity and specificity of the indicated test according to several cut-off values. The dot surrounded by a circle corresponds to the cut-off values generally used for these tests (serum sIL7R=1042 pmol/mL; anti-double-stranded DNA antibodies=50 U/mL; serum C3=85 mg/dL; UPC ratio=0.5). The right panels show the ROC curves of the same tests (several cut-off values), when associated with the necessity of having a serum sIL7R value above the renal cut-off, for the detection of a renal BILAG A.
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LUPUS2014000036F3: Receiving operator characteristic (ROC) curves displaying the performances of serum soluble form of the interleukin-7 receptor (sIL7R) (A), serum anti-double-stranded DNA antibodies (B), serum C3 (C) and urinary protein to creatine (UPC) (D) measurements for the detection of a renal BILAG A in a cohort of SLE nephritis patients. The left panels show the variations in sensitivity and specificity of the indicated test according to several cut-off values. The dot surrounded by a circle corresponds to the cut-off values generally used for these tests (serum sIL7R=1042 pmol/mL; anti-double-stranded DNA antibodies=50 U/mL; serum C3=85 mg/dL; UPC ratio=0.5). The right panels show the ROC curves of the same tests (several cut-off values), when associated with the necessity of having a serum sIL7R value above the renal cut-off, for the detection of a renal BILAG A.

Mentions: Out of the patients with a serum sIL7R value above the renal cut-off, four also had a general, two had a mucocutaneous and one had a neurological BILAG A, in addition to the renal BILAG A (table 2). In patients with serum sIL7R below the renal cut-off, five had a musculo-skeletal, one had a general and one had a mucocutaneous BILAG A during the course of the study. There was no association between sIL7R serum levels and any of these manifestations (data not shown). ROC curves showing the evolution of sIL7R sensitivity and specificity at different cut-off values for the detection of a renal BILAG A are depicted in figure 3. As shown in the same figure, the detection of serum sIL7R concentrations above the renal cut-off improved the specificity of serum dsDNA antibody titres, serum C3 concentrations or UPC ratios for the detection of a renal BILAG A. The diagnostic metrics of the tests are recapitulated in table 3.


sIL7R concentrations in the serum reflect disease activity in the lupus kidney.

Lauwerys BR, Husson SN, Maudoux AL, Badot V, Houssiau FA - Lupus Sci Med (2014)

Receiving operator characteristic (ROC) curves displaying the performances of serum soluble form of the interleukin-7 receptor (sIL7R) (A), serum anti-double-stranded DNA antibodies (B), serum C3 (C) and urinary protein to creatine (UPC) (D) measurements for the detection of a renal BILAG A in a cohort of SLE nephritis patients. The left panels show the variations in sensitivity and specificity of the indicated test according to several cut-off values. The dot surrounded by a circle corresponds to the cut-off values generally used for these tests (serum sIL7R=1042 pmol/mL; anti-double-stranded DNA antibodies=50 U/mL; serum C3=85 mg/dL; UPC ratio=0.5). The right panels show the ROC curves of the same tests (several cut-off values), when associated with the necessity of having a serum sIL7R value above the renal cut-off, for the detection of a renal BILAG A.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225729&req=5

LUPUS2014000036F3: Receiving operator characteristic (ROC) curves displaying the performances of serum soluble form of the interleukin-7 receptor (sIL7R) (A), serum anti-double-stranded DNA antibodies (B), serum C3 (C) and urinary protein to creatine (UPC) (D) measurements for the detection of a renal BILAG A in a cohort of SLE nephritis patients. The left panels show the variations in sensitivity and specificity of the indicated test according to several cut-off values. The dot surrounded by a circle corresponds to the cut-off values generally used for these tests (serum sIL7R=1042 pmol/mL; anti-double-stranded DNA antibodies=50 U/mL; serum C3=85 mg/dL; UPC ratio=0.5). The right panels show the ROC curves of the same tests (several cut-off values), when associated with the necessity of having a serum sIL7R value above the renal cut-off, for the detection of a renal BILAG A.
Mentions: Out of the patients with a serum sIL7R value above the renal cut-off, four also had a general, two had a mucocutaneous and one had a neurological BILAG A, in addition to the renal BILAG A (table 2). In patients with serum sIL7R below the renal cut-off, five had a musculo-skeletal, one had a general and one had a mucocutaneous BILAG A during the course of the study. There was no association between sIL7R serum levels and any of these manifestations (data not shown). ROC curves showing the evolution of sIL7R sensitivity and specificity at different cut-off values for the detection of a renal BILAG A are depicted in figure 3. As shown in the same figure, the detection of serum sIL7R concentrations above the renal cut-off improved the specificity of serum dsDNA antibody titres, serum C3 concentrations or UPC ratios for the detection of a renal BILAG A. The diagnostic metrics of the tests are recapitulated in table 3.

Bottom Line: These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio.Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations.Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE.

View Article: PubMed Central - PubMed

Affiliation: Pôle de pathologies rhumatismales , Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels , Belgium ; Service de Rhumatologie , Cliniques Universitaires Saint-Luc , Brussels , Belgium.

ABSTRACT

Objectives: Evaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study, we reported that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly associated with nephritis in SLE patients. In the present study, we wanted to confirm the association between changes in serum sIL7R concentrations and renal disease activity in a large longitudinal cohort of SLE nephritis patients.

Methods: Sera were harvested longitudinally in 105 SLE nephritis patients. Serum sIL7R cut-off value for the detection of SLE nephritis activity was determined as the mean sIL7R concentration in non-nephritis SLE patients + 2 SDs using data collected in our previous study. Patients with glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (n=17) were excluded from the study due to persistently elevated serum sIL7R values.

Results: Serum sIL7R concentrations above the renal cut-off value were observed in 25 (out of 88) patients with a normal GFR. These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a renal British Isles Lupus Assessment Group index (BILAG) A within the next 3 months, while this was only the case in four out of the 63 other patients (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the detection of a renal BILAG A. Combination of serum sIL7R with any of the classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an increased specificity for the detection of a renal flare. Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations.

Conclusions: Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of an SLE nephritis flare.

No MeSH data available.


Related in: MedlinePlus