Correlation of Serum Interleukin-8 and Cell Surface Lysosome-associated Membrane Protein with Clinical Disease Activity in Systemic Lupus Erythematosus

Abstract

Cell surface expression of lysosome-associated membrane proteins (LAMPs) correlates with serum interleukin-8 (IL-8) levels, shorter disease duration, greater functional impairment from disease-related symptoms and soluble IL-2 receptor levels (sIL-2R) in patients with scleroderma. In this study of 46 patients with systemic lupus erythematosus (SLE), the relationship of serum IL-8 and cell surface LAMP to two clinical measures of disease activity, the SLEDAI and SLAM scales, was evaluated. IL-8 levels were determined on serum samples by the immunometric sandwich enzyme immunoassay technique. Cell surface LAMP expression was determined by flow cytometric quantitation of peripheral blood mononuclear cells with monoclonal antibodies directed against two of the major LAMP proteins, lamp1 and lamp2. The clinical disease activity scales correlated significantly with each other, with C3 levels, serum IL-8, C4, dsDNA and sIL-2R. Lamp1 and lamp2 expression correlated with the SLAM but not the SLEDAI scale. Serum IL-8 levels were elevated in 49 of 51 samples tested (44 of 46 patients) and had a stronger correlation with disease activity than C4, dsDNA and sIL-2R levels. Significantly higher levels of IL-8 were seen in patients with evidence of renal involvement. Serum IL-8 and cell surface LAMP expression may be useful indicators of disease activity in patients with SLE. The possible role of IL-8 in the pathogenesis of SLE requires further investigation.

Keywords

LAMP sIL-2R IL-8 SLEDAI SLAM

Get full access to this article

View all access options for this article.

References

Petri M. , Hellmann D. , Hochberg M. Validity and reliability of lupus activity measures in the routine clinic setting. J Rheumatol 1992; 19: 53-9.

Liang MH , Socher SA , Larson MG , Schur PH Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 1989; 32: 1107-8.

Bombardier C. , Gladman DD , Urowitz MB , Caron D. , Chang CH Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 1992; 35: 630-40.

Ter Borg EJ , Horst G. , Hummer EJ , Limburg PC , Kallenberg Cgm. Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbations in systemic lupus erythematosus: A long-term, prospective study. Arthritis Rheum 1990; 33: 634-43.

Raziuddin S. , Al-Janadi MA , Al-Wabel AA Soluble interleukin-2 receptor levels in serum and its relationship to T cell abnormality and clinical manifestations of disease in patients with systemic lupus erythematosus. J Rheum 1991 ; 18: 831-6.

Ter Borg EJ , Horst G. , Limburg PC , Kallenberg Cgm. Changes in plasma levels of interleukin-2 receptor in relation to disease exacerbations and levels of anti-dsDNA and complement in systemic lupus erythematosus . Clin Exp Immuno 1990 ; 82: 21-6.

Wolf RE , Brelsford WG Soluble interleukin-2 receptors in systemic lupus erythematosus. Arthritis Rheum 1988; 31: 729-35.

Ginzler EM , Antoniadis I. Clinical manifestations of systemic lupus erythematosus, measures of disease activity and long-term complications. Curr Opin Rheumatol 1992 ; 4: 672-80.

Linker-Israeli M. Cytokine abnormalities in human lupus. Clin Immunol Immunopath 1992; 63: 13-16.

10.

Kroemer G. , Martinez AC Cytokines and autoimmune diseases. Clin Immunol Immunopath 1991; 61: 275-95.

11.

Linker-Israeli M. , Deans RJ , Wallace DJ , Prehn J. , Ozeri-Chen T. , Klinenberg JR Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis . J Immunol 1991; 147: 117-23.

12.

Hirohata S. , Miyamoto T. Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 1990; 33: 644-9.

13.

Hardwerger BS Inbred Palmerston North (PN) mice appear to have defective Th1 cell and enhanced Th2 cell function. Arthritis Rheum 1991; 34: S185.

14.

Handwerger BS Abnormalities in interleukin-2 and interleukin-4 production in inbred Palmerston North (PN) mice. Arthritis Rheum 1989; 32: S91.

15.

Handwerger BS T-cell and B-cell function in lupus. Curr Opin Rheumatol 1991 ; 3: 757-79.

16.

Tsokos GC , Boumpas DT , Smith PL , Dieu JY , Balow JE , Rook AH Deficient γ-interferon production in patients with systemic lupus erythematosus . Arthritis Rheum 1986; 29: 1210-15.

17.

DeMaeyer E. , DeMaeyer-Guignard J. Interferon-γ. Curr Opin Immunol 1992; 4: 321-6.

18.

Hebert CA , Luscinsdas FW , Kiely J-M. et al. Endothelial and leukocyte forms of IL-8. J Immunol 1990; 145: 3033-40.

19.

Huber AR , Kunkel SL , Todd RF , Weiss SJ Regulation of trans-endothelial neutrophil migration by endogenous interleukin-8 . Science 1991; 254: 99-102.

20.

Brennan FM , Zachariae CO , Chantry D. , Larsen CG et al. Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol 1990; 20: 2141-4.

21.

Seitz M. , Dewald B. , Ceska M. , Gerber N. , Baggiolini M. Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate. Rheumatol Int 1992; 12: 159-64.

22.

Peichl P. , Ceska M. , Broell H. , Effenberger F. , Linkley IJ Human neutrophil activating peptide/interleukin 8 acts as an autoantigen in rheumatoid arthritis. Ann Rheum Dis 1992 ; 51: 19-22.

23.

Holcombe RF , Baethge BA , Stewart RM et al. Cell surface expression of lysosome-associated membrane proteins (LAMPs) in scleroderma: relationship of lamp2 to disease duration, anti-Sc170 antibodies, serum interleukin-8, and soluble interleukin-2 receptor levels. Clin Immunol Immunopath 1993 ; 67: 31-9.

24.

Reitamo S. , Remitz A. , Varga J. , Ceska M. , Effenberger F. , Jimenez S. , Uitto J. Demonstration of interleukin-8 and autoantibodies to interleukin-8 in the serum of patients with systemic sclerosis and related disorders. Arch Dermatol 1993; 129: 189-93.

25.

Larson CG , Anderson AO , Appella E. , Oppenheim JJ , Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T' lymphocytes . Science 1989; 243: 1464-6.

26.

Sebok K. , Woodside D. , al-Aoukaty A. et al. IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (go) protein. J Immunol 1992; 150: 1524-34.

27.

Fukuda M. Lysosomal membrane glycoproteins. Structure, biosynthesis and intracellular trafficking. J Biol Chem 1991; 266: 21327-30.

28.

Peters PJ , Borst J. , Oorshot V. et al. Cytotoxic T lymphocytes granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med 1991 ; 173: 1099-109.

29.

Silverstein RL , Febbraio M. Identification of lysosome-associated membrane protein-2 as an activation-dependent platelet surface glycoprotein . Blood 1992; 80: 1470-5.

30.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.

31.

Carlsson SR , Roth J. , Filler F. , Fukuda M. Isolation and characterization of human lysosomal membrane glycoproteins h-lamp1 and h-lamp2. J Biol Chem 1988; 263: 18911-19.

32.

Ricker DM , Hebert LA , Rohde R. , Sedmak DD , Lewis EJ , Clough JD and The

Lupus Nephritis Collaborative Study Group. Serum C3 levels are diagnostically more sensitive and specific for systemic lupus erythematosus activity than are serum C4 levels. Am J

Kidney 1991; 18: 678-85.

33.

Wong KL , Wong Rpo. Serum soluble interleukin 2 receptor in systemic lupus erythematosus: effects of disease activity and infection. Ann Rheum Dis 1991; 50: 706-9.

34.

Afterburn LM , McClellan DA , August TA Biosynthesis and processing of lysosomal membrane glycoproteins. In: Intracellular Trafficking of Proteins. Steer CJ & Hanover JA, (eds). New York: Cambridge University Press , 1991, pp. 472-503.

35.

Kom JH Immunologic aspects of scleroderma. Curr Opinion Rheum 1990; 2: 922-8.

36.

Fitzpatrick MM , Shah V. , Trompeter S. , Dillon MJ , Barratt TM Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Kidney Int 1992; 42: 951-6.

37.

Kimata H. , Yoshida A. , Ishioda C. , Lindley I. , Mikawa H. Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by lL-4 in human B cells. J Exp Med 1992; 176: 1227-31.

38.

Hebert CA , Luscinskas FW , Kiely J-M. et al. Endothelial and leukocyte forms of IL-8. J Immunol 1990; 145: 3033-40.

39.

Strieter RM , Phan SH , Schowell HJ et al. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem 1989; 264: 10621-6.