Skip to main content
SpringerLink
Log in

Clinical relapse in systemic lupus erythematosus: Correlation with antecedent elevation of urinary free light-chain immunoglobulin

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

This paper reports preliminary evidence suggesting that measurements of free light-chain Ig (FLIg) in urine may represent quantitative markers ofin vivo polyclonal B-cell activation. Thus, longitudinal levels of urinary FLIg in patients with systemic lupus erythematosus (SLE) may be used to track or monitor thein vivo immunopathologic B-cell activity of SLE and be helpful in predicting a disease relapse. Our findings showed that dramatic rises in urinary FLIg occurred during asymptomatic intervals that preceded by 4–8 weeks the first symptomatic signs of acute SLE relapse. These results suggest that a sizable lead time may exist between the occurrence of immunopathologic B-cell stimulation and the resultant symptoms and tissue damage of immune complex-induced acute inflammation. In these studies the measurement of urinary FLIg was accomplished by an indirect method using ng-sensitive radioimmunoassays (RIAs) that measured isotypic IgG, IgA, IgM, total κ-Ig, and total λ-Ig. As a control for the assessment of renal tubular function and the excretion of low molecular weight proteins in SLE patients, longitudinal measurements of beta-2-microglobulin (B2M) and lysozyme were made using a novel solid-phase3H-biotin RIA technique.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lloyd W, Schur PH: Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus (SLE). Medicine (Baltimore) 60:208–217, 1981

    Google Scholar 

  2. Levinsky RL, Cameron JS, Soothill JF: Serum immune complexes and disease activity in lupus nephritis. Lancet 1:564–567, 1977

    Google Scholar 

  3. Minter MF, Stollar, BD, Agnello V: Reassessment of the clinical significance of native DNA antibodies in systemic lupus erythematosus. Arth Rheum 22:959–968, 1979

    Google Scholar 

  4. Valentijn RM, van Overhagen H, Hazevoet HM, Hermans J, Cats A, Daha MR, van Es LA: the value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus. Arth Rheum 28:904–913, 1985

    Google Scholar 

  5. Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH: Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med 300:518–523, 1979

    Google Scholar 

  6. Emelen W, Mannek M: Clearance of circulating DNA-anti-DNA immune complexes in mice. J Exp Med 155:1210–1215, 1982

    Google Scholar 

  7. Taylor RP, Kujala G, Edberg JC, Foreman P, Davis JS, Wright E: The kinetics of clearance of human antibody/dsDNA immune complexes from rabbit circulation: Effects of dsDNA size, rheumatoid factor, and reduction and alkylation of the antibodies. J Immunol 136:3785–3792, 1986

    Google Scholar 

  8. Hopper JE, Papagiannes E: Evidence by radioimmunoassay that mitogen-activated human blood mononuclear cells secrete significant amounts of light chain Ig unassociated with heavy chain. Cell Immunol 101:122–131, 1986

    Google Scholar 

  9. Waldmann TA, Strober W, Mogielnicki RP: The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 51:2162–2174, 1972

    Google Scholar 

  10. Nisonoff A, Hopper JE, Spring SB: The Antibody Molecule. New York, Academic Press, 1975, pp 254–255

    Google Scholar 

  11. Andres GA, McClusky RT: Tubular and interstitial renal disease due to immunologic mechanisms. Kidney Int 7:271–289, 1975

    Google Scholar 

  12. Brentjens JR, Sepulveda M, Baliah T, Bentzel C, Erlanger BF, Elwood C, Montes M, Hsu KC, Andres GA: Interstitial immune complex nephritis in patients with systemic lupus erythematosus. Kidney Int 7:342–350, 1975

    Google Scholar 

  13. Schwartz MM, Fenell JS, Lewis ET: Pathologic changes in the renal tubule in systemic lupus erythematosus. Hum Pathol 6:534–547, 1982

    Google Scholar 

  14. Hopper, JE, O'Brien, J, Papagiannes, E: Restriction of blood and marrow CLL-B cells to free L-chain Ig secretion: Implication for normal B-cell function and control. Am J Hematol 29:125–133, 1988

    Google Scholar 

  15. Hopper JE: Comparative studies on monotypic IgM-λ and IgG-κ from an individual patient. I. Evidence for shared VH idiotypic determinants. J Immunol 115:1101–1107, 1975

    Google Scholar 

  16. Hopper JE, Brahn E: Structural evidence for an unblocked VHI subgroup of human heavy chains. J Immunol 119:847–849, 1977

    Google Scholar 

  17. Hopper JE, Haren JM, Kmiecik TE: Evidence for shared idiotypy expressed by the IgM, IgA serum proteins of a patient with a complex multiple paraprotein disorder. J Immunol 122:2000–2006, 1979

    Google Scholar 

  18. Porath J, Axen R, Ernback S: Chemical coupling of proteins to agarose. Nature 215:1491–1493, 1967

    Google Scholar 

  19. Hopper JE, Perna L: A solid phase radioimmunoassay technique that utilizes3H-biotin (submitted)

  20. Evrin PE, Peterson PA, Wide L, Berggard I: Radioimmunoassay of B2-microglobulin with human biologic fluids. Scand J Clin Lab Invest 28:439–443, 1971

    Google Scholar 

  21. Portman RJ, Kissane JM, Robson AM: Use of B2 microglobulin to diagnose tubo-interstitial renal lesions in children. Kidney Int 30:91–98, 1986

    Google Scholar 

  22. Thomas MJ, Russo A, Craswell P, Ward M, Steinhardt I: Radioimmunoassay for serum and urinary lysozyme. Clin Chem 27:1223–1226, 1981

    Google Scholar 

  23. Brower J, van Leeuwen-Herberts T, Otting-van de Riut M: Determination of lysozyme in serum, urine, cerebrospinal fluid, and feces by enzyme immunoassay. Clin Chim Acta 142:21–30, 1984

    Google Scholar 

  24. Yamasaki K, Niho Y, Yanase T: Granulopoiesis in systemic lupus erythematosus. Arth Rheum 26:516–521, 1983

    Google Scholar 

  25. Nagasawa T, Sakurai T, Kashiwagi H, Abe T: Cell-mediated amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus. Blood 67:479–483, 1986

    Google Scholar 

  26. Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS: Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med 312:257–265, 1985

    Google Scholar 

  27. Epstein WV: Immunologic events preceding a clinical exacerbation of systemic lupus erythematosus. Am J Med 54:631–636, 1973

    Google Scholar 

  28. Spriggs B, Epstein WV: Clinical and laboratory correlates of L chain proteinuria in systemic lupus erythematosus. J Rheum 1:287–292, 1974

    Google Scholar 

  29. Epstein WV, Grausz H: Favorable outcome in diffuse proliferative glomerulonephritis of systemic lupus erythematosus. Arth Rheum 17:129–142, 1974

    Google Scholar 

  30. Tan M, Epstein WV: A direct immunologic assay of human sera for Bence Jones proteins (L-chains). J Clin Lab Med 66:344–356, 1965

    Google Scholar 

  31. Jerne NK, Roland J, Cozenave PA: Recurrent idiotypes and internal images. EMBO J 1:243–247, 1982

    Google Scholar 

  32. Jorgensen T, Hannestad K: T Helper lymphocytes recognize the VL domain of the isologous mouse myeloma protein 315. Scand J Immunol 10:317–323, 1979

    Google Scholar 

  33. Jorgensen T, Hannestad K: T-Helper cells recognize an iditope located on peptide 88-114/117 of the light chain variable domain of an isologous myeloma protein (315). J Exp Med 158:2183–2188, 1983

    Google Scholar 

  34. Sakato N, Semma M, Eisen NH, Azuma T: A small hypervariable segment in the variable domain of an immunoglobulin light chain stimulates formation of anti idiotypic suppressor T cells. Proc Natl Acad Sci USA 79:5396–5400, 1982

    Google Scholar 

  35. McNamara M, Kohler H: Regulatory idiotypes. Induction of idiotype recognizing helper T cells by free light and heavy chains. J Exp Med 159:623–628, 1984

    Google Scholar 

  36. Jasin HE, Ziff M: Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. Arth Rheum 18:219–228, 1975

    Google Scholar 

  37. Ginsburg WW, Finkelman FD, Lipsky PE: Circulating and pokeweed mitogen-induced immunoglobulin secretory cells in systemic lupus erythematosus. Clin Exp Immunol 35:76–88, 1979

    Google Scholar 

  38. Blaese RM, Grayson J, Steinberg AD: Elevated immunoglobulin secretory cells in the blood of patients with active systemic lupus erythematosus: Correlation of laboratory and clinical assessment of disease activity. Am J Med 69:345–350, 1980

    Google Scholar 

  39. Sakane T, Suzuki N, Takada S, Ueda Y, Murakawa Y, Tsuchida T, Yamauchi Y, Kishimoto T: B cell hyperactivity and its relation to distinct clinical features and the degree of disease activity in patients with systemic lupus erythematosus. Arth Rheum 31:80–87, 1988

    Google Scholar 

  40. Dixon FJ: Murine lupus: A model for human autoimmunity. Arth Rheum 28:1081–1088, 1985

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Hematology, University of Illinois College of Medicine, 60680, Chicago, Illinois

    John E. Hopper, Elaine Papagiannes & Laura Perna

  2. Section of Rheumatology, University of Illinois College of Medicine, 60680, Chicago, Illinois

    Winston Sequeira, Joan Martellotto & John L. Skosey

  3. Division of Rheumatology, Cook County Hospital, 60612, Chicago, Illinois

    Winston Sequeira & Joan Martellotto

Authors
  1. John E. Hopper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Winston Sequeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joan Martellotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elaine Papagiannes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura Perna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John L. Skosey
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hopper, J.E., Sequeira, W., Martellotto, J. et al. Clinical relapse in systemic lupus erythematosus: Correlation with antecedent elevation of urinary free light-chain immunoglobulin. J Clin Immunol 9, 338–350 (1989). https://doi.org/10.1007/BF00918666

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00918666

Key words

Search

Navigation