Natural Regulatory T cells (nTreg) in Minimal Change Disease and IgM Nephropathy

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Yada Louischaroen
Masatha Thongpan
Sansanee C. Chaiyaroj
Prasit Keesukphan
Panas Chalermsanyakorn
Vasant Sumethkul
Chagriya Kitiyakara

Abstract

Background: IgM nephropathy is a variant of minimal change disease (MCD) and is the commonest cause of nephrotic syndrome among Thai adults. Although patients with IgM nephropathy generally respond well to treatment with corticosteroids, patients often have a remitting and relapsing course. The pathogenesis is not well understood. It has been proposed that MCD or IgM nephropathy reflects a disorder of T-lymphocytes. Recently, abnormalities in natural regulatory T cells (nTreg) have been implicated in a number of autoimmune diseases.


Objective: This is a pilot study to examine the number of Foxp3+CD4+ T cells in patients with MCD or IgM nephropathy.


Methods: Eleven patients (2 patients with MDC and 9 patients with IgM nephropathy) and 25 normal control subjects were studied. T cell subpopulations were measured by flow cytometry.


Results: Overall, nTreg were identified by the presence of Foxp3+CD4+ T cells. There were no significant differences in number of CD3+, CD4+ T cells population and Foxp3+CD4+ T cells in MCD/IgM patients compared with normal subjects. In a subgroup analysis, there was a significant increase in Foxp3+CD4+ numbers in untreated MCD/IgM patients with active disease compared to controls.


Conclusion: These results suggesting correlation between activation of immune system in pathogenesis. Natural regulatory T cell as detected with Foxp3+CD4+ was increased in active MCD/IgM nephropathy patients.

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How to Cite
1.
Louischaroen Y, Thongpan M, C. Chaiyaroj S, Keesukphan P, Chalermsanyakorn P, Sumethkul V, Kitiyakara C. Natural Regulatory T cells (nTreg) in Minimal Change Disease and IgM Nephropathy. Rama Med J [Internet]. 2018 Apr. 3 [cited 2024 Mar. 28];35(1):19-30. Available from: https://he02.tci-thaijo.org/index.php/ramajournal/article/view/117741
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References

Saha TC, Singh H. Minimal change disease: a review. South Med J. 2006;99(11):1264-70. doi:10.1097/01.smj.0000243183.87381.c2.

Cho MH, Hong EH, Lee TH, Ko CW. Pathophysiology of minimal change nephrotic syndrome and focal segmental glomerulosclerosis. Nephrology (Carlton). 2007;12 Suppl 3:S11-4. doi:10.1111/j.1440-1797.2007.00875.x.

Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis. 1997;30(5):621-31. doi:10.1016/s0272-6386(97)90485-6.

Maruyama M, Toyoda M, Umezono T, Miyauchi M, Yamamoto N, Kimura M, et al. [Clinical significance of IgM deposition in the mesangium and mesangial hypercellularity in adult minimal change nephrotic syndrome]. Nihon Jinzo Gakkai Shi. 2006;48(1):14-21.

Matsukura H, Higuchi O, Arai M, Itoh Y, Miyawaki T. Minimal change variants: IgM nephropathy. Clin Nephrol. 2006;65(2):147-9. doi:10.5414/cnp65147.

Sumethkul V, Sakulsaengprapha A, Chalermsanyakorn P, Indraprasit S. Survival analysis of Thai patients with IgM nephropathy, focal segmental glomerulosclerosis and membranous nephrotic syndrome. J Med Assoc Thai. 2000;83 Suppl 1:S123-9.

Al-Eisa A, Carter JE, Lirenman DS, Magil AB. Childhood IgM nephropathy: comparison with minimal change disease. Nephron. 1996;72(1):37-43. doi:10.1159/000188804.

Uda S, Nakayama T, Hirose M, Yoshimura A. [Minimal change nephrotic syndrome]. Nihon Rinsho. 2004;62(10):1829-36.

Tse KC, Lam MF, Yip PS, Li FK, Choy BY, Lai KN, et al. Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses. Nephrol Dial Transplant. 2003;18(7):1316-20. doi:10.1093/ndt/gfg134.

Nakayama M, Katafuchi R, Yanase T, Ikeda K, Tanaka H, Fujimi S. Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome. Am J Kidney Dis. 2002;39(3):503-12. doi:10.1053/ajkd.2002.31400.

Bernstein J Jr, Edelmann CM Jr. Minimal change nephrotic syndrome. Histopathology and steroid-responsiveness. Arch Dis Child. 1982;57(11):816-7. doi:10.1136/adc.57.11.816.

Esposito C, Striker LJ, Gary E. Molecular analysis of glomerular diseases in renal biopsies. Nephrology. 1997;3(S2):683-9. doi:10.1111/j.1440-1797.1997.tb00285.x.

Valencia X, Lipsky PE. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Clin Pract Rheumatol. 2007;3(11):619-26. doi:10.1038/ncprheum0624.

Hsu WT, Suen JL, Chiang BL. The role of CD4CD25 T cells in autoantibody production in murine lupus. Clin Exp Immunol. 2006;145(3):513-9. doi:10.1111/j.1365-2249.2006.03173.x.

Cao D, Börjesson O, Larsson P, Rudin A, Gunnarsson I, Klareskog L, et al. FOXP3 identifies regulatory CD25bright CD4+ T cells in rheumatic joints. Scand J Immunol. 2006;63(6):444-52. doi:10.1111/j.1365-3083.2006.001755.x.

Poussier P, Ning T, Murphy T, Dabrowski D, Ramanathan S. Impaired post-thymic development of regulatory CD4+25+ T cells contributes to diabetes pathogenesis in BB rats. J Immunol. 2005;174(7):4081-9. doi:10.4049/jimmunol.174.7.4081.

Strickland DH, Stumbles PA, Zosky GR, Subrata LS, Thomas JA, Turner DJ, et al. Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J Exp Med. 2006;203(12):2649-60. doi:10.1084/jem.20060155.

Larché M. Immunoregulation by targeting T cells in the treatment of allergy and asthma. Curr Opin Immunol. 2006;18(6):745-50. doi:10.1016/j.coi.2006.09.013.

Umetsu DT, DeKruyff RH. The regulation of allergy and asthma. Immunol Rev. 2006;212:238-55. doi:10.1111/j.0105-2896.2006.00413.x.

Ménager-Marcq I, Pomié C, Romagnoli P, van Meerwijk JP. CD8+CD28- regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice. Gastroenterology. 2006;131(6):1775-85. doi:10.1053/j.gastro.2006.09.008.

Holmén N, Lundgren A, Lundin S, Bergin AM, Rudin A, Sjövall H, et al. Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis. 2006;12(6):447-56. doi:10.1097/00054725-200606000-00003.

Tomer Y, Shoenfeld Y. The significance of T suppressor cells in the development of autoimmunity. J Autoimmun. 1989;2(6):739-58.

Yoshizawa N, Kusumi Y, Matsumoto K, Oshima S, Takeuchi A, Kawamura O, et al. Studies of a glomerular permeability factor in patients with minimal-change nephrotic syndrome. Nephron. 1989;51(3):370-6. doi:10.1159/000185325.

Maruyama K, Tomizawa S, Shimabukuro N, Fukuda T, Johshita T, Kuroume T. Effect of supernatants derived from T lymphocyte culture in minimal change nephrotic syndrome on rat kidney capillaries. Nephron. 1989;51(1):73-6. doi:10.1159/000185246.

Tanaka R, Yoshikawa N, Nakamura H, Ito H. Infusion of peripheral blood mononuclear cell products from nephrotic children increases albuminuria in rats. Nephron. 1992;60(1):35-41. doi:10.1159/000186702.

Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet. 1974;2(7880):556-60. doi:10.1016/s0140-6736(74)91880-7.

Koyama A, Fujisaki M, Kobayashi M, Igarashi M, Narita M. A glomerular permeability factor produced by human T cell hybridomas. Kidney Int. 1991;40(3):453-60. doi:10.1038/ki.1991.232.

Bagga A, Vasudev AS, Moudgil A, Srivastava RN. Peripheral blood lymphocyte subsets in idiopathic nephrotic syndrome of childhood. Indian J Med Res. 1996;104:292-5.

Bharat A, Fields RC, Mohanakumar T. Regulatory T cell-mediated transplantation tolerance. Immunol Res. 2005;33(3):195-212. doi:10.1385/IR:33:3:195.

Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003;4(4):337-42. doi:10.1038/ni909.

Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005;22(3):329-41. doi:10.1016/j.immuni.2005.01.016.

Kobayashi K, Yoshikawa N, Nakamura H. T-cell subpopulations in childhood nephrotic syndrome. Clin Nephrol. 1994;41(5):253-8.

Lobzin IuV, Nikitin VIu, Sukhina IA, Tsygan VN, Mitin IuA. [Immunopathogenesis of viral hepatitis C. Immunological markers of the disease progression]. Zh Mikrobiol Epidemiol Immunobiol. 2007;(6):75-84.

Araujo FF, Gomes JA, Rocha MO, Williams-Blangero S, Pinheiro VM, Morato MJ, et al. Potential role of CD4+CD25HIGH regulatory T cells in morbidity in Chagas disease. Front Biosci. 2007;12:2797-806.

Bergsma DJ, Eder C, Gross M, Kersten H, Sylvester D, Appelbaum E. The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. J Biol Chem. 1991;266(34):23204-14.