Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Jul;76(1):341–349. doi: 10.1172/JCI111967

Identification of the lymphokine soluble immune response suppressor in urine of nephrotic children.

H W Schnaper, T M Aune
PMCID: PMC423781  PMID: 4019784

Abstract

Patients with minimal change nephrotic syndrome (MCNS) frequently have suppressed in vivo and in vitro immune responsiveness of uncertain etiology. Because increased suppressor cell activity has been associated with this disease, urines from MCNS patients were screened for activity of the lymphokine soluble immune response suppressor (SIRS), a product of concanavalin A- or interferon-activated suppressor T cells. Urines from untreated MCNS patients suppressed polyclonal plaque-forming cell responses of cultured splenocytes. This suppressive activity was identified as human SIRS by the following functional and physical criteria: molecular weight estimated by gel filtration; kinetics of suppression; inhibition of suppression by catalase, levamisole, and 2-mercaptoethanol; abrogation of activity by acid or protease treatment; elution pattern on high performance liquid chromatography; and cross-reactivity with monoclonal antimurine SIRS antibodies. Suppressive activity disappeared from urine after initiation of treatment but before remission of symptoms. Urines were tested from 11 patients with MCNS, all of whom excreted SIRS. In addition, two nephrotic patients with acute glomerulonephritis and three nephrotic patients with membranoproliferative disease excreted SIRS, but other nephrotics and all nonnephrotic patients did not. These results indicate that excretion of SIRS occurs in certain cases of nephrotic syndrome and that the presence of SIRS in the urine is not accounted for solely by the presence of proteinuria or nephrosis. Serum from four nephrotic patients also contained SIRS, whereas neither serum nor urine from six normal subjects contained SIRS activity. The systemic presence of SIRS in these four patients, and the identification of SIRS in urines from a larger group of patients, suggest a possible role for SIRS in the suppressed immune responses often found in nephrotic syndrome.

Full text

PDF
341

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aune T. M., Pierce C. W. Activation of a suppressor T-cell pathway by interferon. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3808–3812. doi: 10.1073/pnas.79.12.3808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aune T. M., Webb D. R., Pierce C. W. Purification and initial characterization of the lymphokine soluble immune response suppressor. J Immunol. 1983 Dec;131(6):2848–2852. [PubMed] [Google Scholar]
  3. Barna B. P., Makker S., Kallen R., Valenzuela R., Deodhar S. D., Yeip M., Leto D., Verbic M. A., Rajaraman S., Govindarajan S. A lymphocytotoxic factor(s) in plasma of patients with minimal change nephrotic syndrome: partial characterization. Clin Immunol Immunopathol. 1983 May;27(2):272–282. doi: 10.1016/0090-1229(83)90077-6. [DOI] [PubMed] [Google Scholar]
  4. Beale M. G., Hoffsten P. E., Robson A. M., MacDermott R. P. Inhibitory factors of lymphocyte transformation in sera from patients with minimal change nephrotic syndrome. Clin Nephrol. 1980 Jun;13(6):271–276. [PubMed] [Google Scholar]
  5. Brenner B. M., Hostetter T. H., Humes H. D. Molecular basis of proteinuria of glomerular origin. N Engl J Med. 1978 Apr 13;298(15):826–833. doi: 10.1056/NEJM197804132981507. [DOI] [PubMed] [Google Scholar]
  6. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  7. Fodor P., Saitúa M. T., Rodriguez E., González B., Schlesinger L. T-cell dysfunction in minimal-change nephrotic syndrome of childhood. Am J Dis Child. 1982 Aug;136(8):713–717. doi: 10.1001/archpedi.1982.03970440057016. [DOI] [PubMed] [Google Scholar]
  8. Giangiacomo J., Cleary T. G., Cole B. R., Hoffsten P., Robson A. M. Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome. N Engl J Med. 1975 Jul 3;293(1):8–12. doi: 10.1056/NEJM197507032930103. [DOI] [PubMed] [Google Scholar]
  9. Grupe W. E. Childhood nephrotic syndrome: clinical associations and response to therapy. Postgrad Med. 1979 May;65(5):229-31, 234-6. doi: 10.1080/00325481.1979.11715153. [DOI] [PubMed] [Google Scholar]
  10. Heslan J. M., Lautie J. P., Intrator L., Blanc C., Lagrue G., Sobel A. T. Impaired IgG synthesis in patients with the nephrotic syndrome. Clin Nephrol. 1982 Sep;18(3):144–147. [PubMed] [Google Scholar]
  11. Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iitaka K., West C. D. A serum inhibitor of blastogenesis in idiopathic nephrotic syndrome transferred by lymphocytes. Clin Immunol Immunopathol. 1979 Jan;12(1):62–71. doi: 10.1016/0090-1229(79)90111-9. [DOI] [PubMed] [Google Scholar]
  13. Irons R. D., Pfeifer R. W., Aune T. M., Pierce C. W. Soluble immune response suppressor (SIRS) inhibits microtubule function in vivo and microtubule assembly in vitro. J Immunol. 1984 Oct;133(4):2032–2036. [PubMed] [Google Scholar]
  14. Kawakita M., Miyake T., Kishimoto S., Ogawa M. Apparent heterogeneity of human megakaryocyte colony- and thrombopoiesis-stimulating factors: studies on urinary extracts from patients with aplastic anaemia and idiopathic thrombocytopenic purpura. Br J Haematol. 1982 Nov;52(3):429–438. doi: 10.1111/j.1365-2141.1982.tb03912.x. [DOI] [PubMed] [Google Scholar]
  15. Kerpen H. O., Bhat J. G., Kantor R., Gauthier B., Rai K. R., Schacht R. G., Baldwin D. S. Lymphocyte subpopulations in minimal change nephrotic syndrome. Clin Immunol Immunopathol. 1979 Sep;14(1):130–136. doi: 10.1016/0090-1229(79)90133-8. [DOI] [PubMed] [Google Scholar]
  16. Kimball E. S., Pickeral S. F., Oppenheim J. J., Rossio J. L. Interleukin 1 activity in normal human urine. J Immunol. 1984 Jul;133(1):256–260. [PubMed] [Google Scholar]
  17. Kreisberg J. I., Wayne D. B., Karnovsky M. J. Rapid and focal loss of negative charge associated with mononuclear cell infiltration early in nephrotoxic serum nephritis. Kidney Int. 1979 Sep;16(3):290–300. doi: 10.1038/ki.1979.131. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Lenarsky C., Jordan S. C., Ladisch S. Plasma inhibition of lymphocyte proliferation in nephrotic syndrome: correlation with hyperlipidemia. J Clin Immunol. 1982 Oct;2(4):276–281. doi: 10.1007/BF00915067. [DOI] [PubMed] [Google Scholar]
  20. Mallick N. P., Williams R. J., McFarlane H., Orr W. M., Taylor G., Williams G. Cell-mediated immunity in nephrotic syndrome. Lancet. 1972 Mar 4;1(7749):507–509. doi: 10.1016/s0140-6736(72)90174-2. [DOI] [PubMed] [Google Scholar]
  21. Martini A., Vitiello M. A., Siena S., Capelli V., Ugazio A. G. Multiple serum inhibitors of lectin-induced lymphocyte proliferation in nephrotic syndrome. Clin Exp Immunol. 1981 Jul;45(1):178–184. [PMC free article] [PubMed] [Google Scholar]
  22. Moorthy A. V., Zimmerman S. W., Burkholder P. M. Inhibition of lymphocyte blastogenesis by plasma of patients with minimal-change nephrotic syndrome. Lancet. 1976 May 29;1(7970):1160–1162. doi: 10.1016/s0140-6736(76)91545-2. [DOI] [PubMed] [Google Scholar]
  23. Ooi B. S., Orlina A. R., Masaitis L. Lymphocytotoxins in primary renal disease. Lancet. 1974 Dec 7;2(7893):1348–1350. doi: 10.1016/s0140-6736(74)92215-6. [DOI] [PubMed] [Google Scholar]
  24. Osakabe K., Matsumoto K. Concanavalin A-induced suppressor cell activity in lipoid nephrosis. Scand J Immunol. 1981 Aug;14(2):161–165. doi: 10.1111/j.1365-3083.1981.tb00196.x. [DOI] [PubMed] [Google Scholar]
  25. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation. 3. Suppression of plaque-forming cell responses in vitro by supernatant fluids from concanavalin A-activated spleen cell cultures. J Immunol. 1974 Apr;112(4):1360–1368. [PubMed] [Google Scholar]
  26. Schnaper H. W., Aune T. M., Pierce C. W. Suppressor T cell activation by human leukocyte interferon. J Immunol. 1983 Nov;131(5):2301–2306. [PubMed] [Google Scholar]
  27. Schnaper H. W., Pierce C. W., Aune T. M. Identification and initial characterization of concanavalin A- and interferon-induced human suppressor factors: evidence for a human equivalent of murine soluble immune response suppressor (SIRS). J Immunol. 1984 May;132(5):2429–2435. [PubMed] [Google Scholar]
  28. Schreiner G. F., Cotran R. S., Pardo V., Unanue E. R. A mononuclear cell component in experimental immunological glomerulonephritis. J Exp Med. 1978 Feb 1;147(2):369–384. doi: 10.1084/jem.147.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shalhoub R. J. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet. 1974 Sep 7;2(7880):556–560. doi: 10.1016/s0140-6736(74)91880-7. [DOI] [PubMed] [Google Scholar]
  30. Steinberg A. D., Smith H. R., Laskin C. A., Steinberg B. J., Smolen J. S. Studies of immune abnormalities in systemic lupus erythematosus. Am J Kidney Dis. 1982 Jul;2(1 Suppl 1):101–110. [PubMed] [Google Scholar]
  31. Sweet G. H., Welborn F. L. Use of chromium chloride as the coupling agent in a modified plaque assay. Cells producing anti-protein antibody. J Immunol. 1971 May;106(5):1407–1410. [PubMed] [Google Scholar]
  32. Tanphaichitr P., Tanphaichitr D., Sureeratanan J., Chatasingh S. Treatment of nephrotic syndrome with levamisole. J Pediatr. 1980 Mar;96(3 Pt 1):490–493. doi: 10.1016/s0022-3476(80)80707-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES