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• W2094365312 abstract "To the Editor: We read with great interest the commentary by Jefferson and Shankland,1.Jefferson J.A. Shankland S.J. Has the circulating permeability factor in primary FSGS been found?.Kidney Int. 2013; 84: 235-238Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar as well as the original research by Huang et al.2.Huang J. Liu G. Zhang Y.M. et al.Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis.Kidney Int. 2013; 84: 366-372Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Huang et al.2.Huang J. Liu G. Zhang Y.M. et al.Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis.Kidney Int. 2013; 84: 366-372Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar reported that the soluble urokinase-type plasminogen activator receptor (suPAR), a possible circulating permeability factor, was significantly higher in patients with primary focal segmental glomerulosclerosis (FSGS) than in those with minimal-change disease, membranous nephropathy, and normal individuals. However, they did not explain why suPAR levels of patients with FSGS are increased. Thus, we would like to present a potential mechanism. Although the exact etiology of FSGS still remains elusive, serum interleukin-2 (IL-2) has been implicated in the pathogenesis of FSGS. Jordan et al.3.Jordan S.C. Querfeld U. Toyoda M. et al.Serum interleukin-2 levels in a patient with focal segmental glomerulosclerosis. Relationship to clinical course and cyclosporin A therapy.Pediatr Nephrol. 1990; 4: 166-168Crossref PubMed Scopus (15) Google Scholar found that IL-2 levels were markedly elevated in association with disease activity in a patient with FSGS. The patient achieved remission and serum IL-2 decreased to undetectable levels after cyclosporin treatment. However, the patient relapsed and the serum IL-2 levels were elevated again after cessation of cyclosporin.3.Jordan S.C. Querfeld U. Toyoda M. et al.Serum interleukin-2 levels in a patient with focal segmental glomerulosclerosis. Relationship to clinical course and cyclosporin A therapy.Pediatr Nephrol. 1990; 4: 166-168Crossref PubMed Scopus (15) Google Scholar Reinstitution of cyclosporin was followed by a partial remission of the disease and disappearance of detectable serum IL-2 levels.3.Jordan S.C. Querfeld U. Toyoda M. et al.Serum interleukin-2 levels in a patient with focal segmental glomerulosclerosis. Relationship to clinical course and cyclosporin A therapy.Pediatr Nephrol. 1990; 4: 166-168Crossref PubMed Scopus (15) Google Scholar Moreover, Cather et al.4.Cather J.C. Jackow C. Yegge J. et al.Mycosis fungoides with focal segmental glomerular sclerosis and nephrotic syndrome.J Am Acad Dermatol. 1998; 38: 301-305Abstract Full Text Full Text PDF PubMed Google Scholar reported the first two cases of FSGS, which developed in patients with cutaneous T-cell lymphoma (Sezary syndrome), in which soluble IL-2 receptors seemed to be the most sensitive marker and is typically increased, and they suggested that IL-2 could be related to glomerular injury in these patients.4.Cather J.C. Jackow C. Yegge J. et al.Mycosis fungoides with focal segmental glomerular sclerosis and nephrotic syndrome.J Am Acad Dermatol. 1998; 38: 301-305Abstract Full Text Full Text PDF PubMed Google Scholar,5.Hassel J.C. Meier R. Joller-Jemelka H. et al.Serological immunomarkers in cutaneous T cell lymphoma.Dermatology. 2004; 209: 296-300Crossref PubMed Scopus (28) Google Scholar According to a previous study by Al-Atrash et al.,6.Al-Atrash G. Shetty S. Idell S. et al.IL-2-mediated upregulation of uPA and uPAR in natural killer cells.Biochem Biophys Res Commun. 2002; 292: 184-189Crossref PubMed Scopus (16) Google Scholar IL-2 upregulated both urokinase plasminogen activator (uPA) and its receptor uPAR in natural killer cells. An induction of uPAR mRNA and a reciprocal downregulation of uPAR mRNA–binding proteins were observed after IL-2 stimulation.6.Al-Atrash G. Shetty S. Idell S. et al.IL-2-mediated upregulation of uPA and uPAR in natural killer cells.Biochem Biophys Res Commun. 2002; 292: 184-189Crossref PubMed Scopus (16) Google Scholar Furthermore, Nykjaer et al.7.Nykjaer A. Møller B. Todd 3rd, R.F. et al.Urokinase receptor. An activation antigen in human T lymphocytes.J Immunol. 1994; 152: 505-516PubMed Google Scholar demonstrated that IL-2 increased uPAR presentation on 20–50% of the T-cell population. Recently, Shishido et al.8.Shishido S. Satou H. Muramatsu M. et al.Combination of pulse methylprednisolone infusions with cyclosporine-based immunosuppression is safe and effective to treat recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation.Clin Transplant. 2013; 27: E143-E150Crossref PubMed Scopus (23) Google Scholar reported that recurrent FSGS after kidney transplantation, which might be considered to be caused by circulating factors, was successfully treated with immunosuppressive treatments with high-dose methylprednisolone infusion therapy and cyclosporin, which could suppress IL-2 levels.9.Wandinger K.P. Wessel K. Trillenberg P. et al.Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients.Acta Neurol Scand. 1998; 97: 359-365Crossref PubMed Scopus (42) Google Scholar Therefore, there is a possibility that elevated IL-2 might increase suPAR in patients with FSGS and the increased levels of suPAR could be reversed by blocking IL-2. Further studies are necessary to test this hypothesis as a confirmation and develop new pharmacological interventions to treat FSGS. This letter was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A1012112)." @default.
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• W2094365312 title "Elevated soluble urokinase receptors in focal segmental glomerulosclerosis: a role for IL-2?" @default.
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