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Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) Gene Expression and Urinary CTLA4 Levels in Idiopathic Nephrotic Syndrome

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Abstract

Objectives

To detect Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) single nucleotide polymorphisms (SNPs) at +49A/G (rs231775) and -318C/T (rs5742909) positions in children with idiopathic nephrotic syndrome (INS) and also assay urinary soluble CTLA4 (sCTLA4) levels in children with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and steroid sensitive nephrotic syndrome (SSNS) in remission.

Methods

The study included 59 patients of INS (MCD-23, FSGS-15 and SSNS in remission-21) and 35 healthy controls. The CTLA4 SNPs profiling was done in peripheral blood mononuclear cells and urinary sCTLA4 level was assayed by ELISA kit.

Results

Although frequency of homozygous +49 GG (rs4553808) genotype (26.3% vs. 11.4%; p = 0.231) and G allele (52.6% vs. 40%; p = 0.216) were found to be higher in INS as compared to controls, the differences were statistically non-significant. Genotypes GG, AG, AA and alleles A and G frequencies were comparable among MCD, FSGS and controls. SNP at −318 C/T (rs5742909) did not show homozygous TT genotype both in INS as well as controls. Median urinary sCTLA4/creatinine level was significantly higher in MCD as compared to FSGS (p = 0.027), SSNS in remission (p = 0.001) and controls (p = 0.003).

Conclusions

The positive associations of +49 GG genotype and G allele in patients with nephrotic syndrome were not observed. The frequencies did not differ significantly among MCD, FSGS and controls. Urinary sCTLA4 level was significantly increased in MCD; suggesting its possible role in the pathogenesis of disease.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Om P Mishra, Prashant Chhabra, Rajniti Prasad, Ankur Singh & Abhishek Abhinay

  2. Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India

    Gopeshwar Narayan

  3. Department of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India

    Pradeep Srivastava

  4. Department of Pathology, G.B. Pant Hospital, New Delhi, India

    Vineeta V Batra

Authors
  1. Om P Mishra
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  2. Prashant Chhabra
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  3. Gopeshwar Narayan
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  4. Pradeep Srivastava
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  5. Rajniti Prasad
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  6. Ankur Singh
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  7. Abhishek Abhinay
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  8. Vineeta V Batra
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Contributions

OPM, PC and RP: Involved in the study design, conduction, data analysis and drafting of manuscript; AS, AA: Helped in data analysis and drafting of manuscript; GN: Helped in genetic analysis; PS: Performed assay of urinary sCTLA4; VVB: Examined the histopathology of renal tissues. OPM will act as guarantor for this paper.

Corresponding author

Correspondence to Om P Mishra.

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None.

Source of Funding

The study was supported by the Institutional Grants of Department of Pediatrics, Institute of Medical Sciences and School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.

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Mishra, O.P., Chhabra, P., Narayan, G. et al. Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) Gene Expression and Urinary CTLA4 Levels in Idiopathic Nephrotic Syndrome. Indian J Pediatr 86, 26–31 (2019). https://doi.org/10.1007/s12098-018-2734-9

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  • DOI: https://doi.org/10.1007/s12098-018-2734-9

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