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01-08-2017 | Original Article

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome

Authors: Om P. Mishra, Ravindra Kumar, Gopeshwar Narayan, Pradeep Srivastava, Abhishek Abhinay, Rajniti Prasad, Ankur Singh, Vineeta V. Batra

Published in: Pediatric Nephrology | Issue 8/2017

Abstract

Background

The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS).

Methods

The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated.

Results

Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678–0.978, p = 0.002) for the diagnosis of MCD.

Conclusions

Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.

Constantinescu AR, Shah HE, Foote EF, Weiss LS (2000) Predicting first year relapses in children with nephrotic syndrome. Pediatrics 105:492–495CrossRefPubMed

Sharples PM, Poulton J, White RHR (1995) Steroid-responsive nephrotic syndrome is more common in Asians. Arch Dis Child 60:1014–1017CrossRef

Eddy AA, Symons JM (2003) Nephrotic syndrome in childhood. Lancet 362:629–639CrossRefPubMed

Srivastava T, Simon SD, Alon US (1999) High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. Pediatr Nephrol 13:13–18CrossRefPubMed

Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA (2009) Management of childhood onset nephrotic syndrome. Pediatrics 124:747–757CrossRefPubMed

Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560CrossRefPubMed

Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA, Mundel P (2004) Induction of B7–1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113:1390–1397CrossRefPubMedPubMedCentral

Ishimoto T, Cara-Fuentes G, Wang H, Shimada M, Wasserfall CH, Winter WE, Rivard CJ, Araya CE, Saleem MA, Mathieson PW, Johnson RJ, Garin EH (2013) Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes. Pediatr Nephrol 28:1803–1812CrossRefPubMedPubMedCentral

Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, Johnson RJ (2009) Urinary CD80 excretion increases in idiopathic minimal change disease. J Am Soc Nephrol 20:260–266CrossRefPubMedPubMedCentral

10.

Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M (2010) Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int 78:296–302CrossRefPubMed

11.

Shimada M, Ishimoto T, Lee PY, Lanaspa MA, Rivard CJ, Roncal-Jimenez CA, Wymer DT, Yamabe H, Mathieson PW, Saleem MA, Garin EH, Johnson RJ (2012) Toll‐like receptor 3 ligands induce CD80 expression in human podocytes via an NF‐kappa B‐dependent pathway. Nephrol Dial Transplant 27:81–89CrossRefPubMed

12.

Srivastava T, Sharma M, Yew KH, Sharma R, Duncan RS, Saleem MA, McCarthy ET, Kats A, Cudmore PA, Alon US, Harrison CJ (2013) LPS and PAN‐induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile. J Cell Commun Signal 7:49–60CrossRefPubMed

13.

Wahyono T, Subandiyah K, Fitri LE, Endharti AT (2014) Toll like receptor 4(Tlr4) and p65 nuclear factor kappa b (Nf-ĸb) expression in monocyte cell of children with steroid resistant nephrotic syndrome. J Trop Life Sci 4:82–88CrossRef

14.

Indian Pediatric Nephrology Group, Indian Academy of Pediatrics, Bagga A, Ali U, Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, Sethi S, Shah M (2008) Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr 45:203–214

15.

Gulati A, Bagga A, Gulati S, Mehta KP, Vijayakumar M (2009) Indian Society of Pediatric Nephrology. Management of steroid resistant nephrotic syndrome. Indian Pediatr 46:35–47PubMed

16.

Das M, Prasad SB, Yadav SS, Govardhan HB, Pandey LK, Singh S, Pradhan S, Narayan G (2013) Overexpression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One 8:e69607CrossRefPubMedPubMedCentral

17.

Jamin A, Dehoux L, Dossier C, Fila M, Heming N, Monteiro RC, Deschênes G (2015) Toll-like receptor 3 expression and function in childhood idiopathic nephrotic syndrome. Clin Exp Immunol 182:332–345CrossRefPubMedPubMedCentral

18.

Navarro-Muñoz M, Ibernon M, Pérez V, Ara J, Espinal A, López D, Bonet J, Romero R (2011) Messenger RNA expression of B7-1 and NPHS1 in urinary sediment could be useful to differentiate between minimal change disease and focal segmental glomerulosclerosis in adult patients. Nephrol Dial Transplant 26:3914–3923CrossRefPubMed

19.

Cara-Fuentes G, Wei C, Segarra A, Ishimoto T, Rivard C, Johnson RJ, Reiser J, Garin EH (2014) CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol 29:1363–1371CrossRefPubMed

20.

Ling C, Liu X, Shen Y, Chen Z, Fan J, Jiang Y, Meng Q (2015) Urinary CD80 levels as a diagnostic biomarker of minimal change disease. Pediatr Nephrol 30:309–316CrossRefPubMed

21.

Zeybek C, Hacıhamdioğlu DO, Yavuz ST, Pekel A, Akgün C, Bulum B, Gülleroğlu K, Kantar A, Kavaz A, Muşabak U, Yalçınkaya F, Baskın E, Gök F (2014) The roles of urine interleukin-13, CD80, CD28, matrix metalloproteinase-2 and granzyme B in the pathogenesis of childhood minimal change nephrotic syndrome. J Clin Exp Invest 5:354–361CrossRef

Title: Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome
Authors: Om P. Mishra
Ravindra Kumar
Gopeshwar Narayan
Pradeep Srivastava
Abhishek Abhinay
Rajniti Prasad
Ankur Singh
Vineeta V. Batra
Publication date: 01-08-2017
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 8/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-017-3613-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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