Monitoring of Disease Biomarkers Activity and Immunophenotyping as Important Factors in SLE Clinical Management
Djemo Subasic, Jasenko Karamehic¹ Marina Delic-Sarac¹, Mersija Kasumovic, Mevludin Mekic, Izet Eminovic, Nermina Hasanagic
Med Arh. 2012; 66(5): 336-339

View PDF Fulltext


The highly specific biomarkers for monitoring of SLE disease activity are not yet defined up to date, due to existing of different clinical SLE phenotypes caused by individual genetic variation. Basically, numerous clinical complications follow SLE patients such as nephritis, atherosclerosis and cardial, CNS, gastrointestinal and ophthalmological complications, as well. Their monitoring in clinical SLE management can be evaluated by analysing of specific biochemical parameters and require permanent clinical observation. The presence of ANAs and anti-ds-DNAs are usual diagnostic SLE autoimmunity parameters, while SLE disease activity biomarkers are C3 and C4 level, anticardiolipin antibodies, anti-Sm/RNPs and, recently level of CD4 and CD8 lymphocytes. However, the number of TCR molecules on the T-cells surface at SLE patients is lower then in normal condition, and otherwise for these receptors CD molecules make specific connection. On the other hand, the T lymphocytes can be also, therapeutical targets at SLE patients, beacause of their clear direct involving in SLE pathogenesis. The SLE phenotypes are characterized by double CD negativity ( CD3+/-, CD4-) caused by abnormal level of IL-2 and IL-17. T-lymphocytes have usually alpha-beta and gamma-delta TCR receptors, but for SLE patients is characteristic lower number gama-delta TCR molecules, detected in the peripheral blood specimens. Taking into account all of the facts, we investigated the level of specific usual SLE activity biomarkers (anti-ds-DNAs, C3, C4, anticardiolipin antibodies (beta-2-IgG, beta-2-IgM, ACA-G, ACA-M, CD4 and CD8 level) in serum specimens of SLE patients who underwent to the corresponding chemotherapy in combination with other biochemical and clinical parameters. Once again proved to be, that SLE biomarker monitoring, could be useful aproach for SLE activity disease and prediction organ damage, as well. In our investigation we used the following methods: immunofluorescence microscopy (IFA-ANA), and nephelometry, Hycor ELISA system and Flow cytometry, for precisely quantitative measurements. We determined correlation between C3 and C4 complement components level, CD3 (T-Ly), CD3+/HLA-DR and total HLA-DR with regard to SLE disease activity. Also, CD4 (Th), CD4:CD8 ratio, beta-2-G, beta-2-M not proved to be useful biomarkers in this sense, despite some results specific for some special SLE phenotypes. Anti-Sm/RNPs proved to be better in SLE diagnostic process.


1. Doyle HA, Yan J, Liang B, Mamula MJ. Lupus autoantigens: their origins, forms, and presentation. Immunol. Res. 2001; 24; 131-147.

2. Tan EM. Autoantibodies to nuclear antigens: Their immunobiology and medicine. Adv Imm. 1982; 33: 167-239.

3. Wakeland EK, Liu K, Graham RR, Behrens TW. Delineating the genetic basis of systemic lupus erythematosus. Immunity. 2001, 15: 397-408.

4. Gaffney PM, Moser KL, Graham RR, Behrens TW. Recent advances in the genetics of systemic lupus erythematosus. Rheum Dis Clin North Am 2002, 28: 111-126.

5. Okumura N, Nomura M, Tada T. Effects of sample storage on serum C3 assay by immunonephelometry. Clin Lab Sci. 1990; 3; 54-57.

6. Cohen M. Systemic Lupus Erythematosus: diagnosis and classification. Intern Med J. 2004; 34(12): 701-702.

7. Deng YJ, Huang ZX, Zhou CJ, Wang JW, You Y, Song ZQ, Xiang MM, Zhong BY, Hao F. Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus. Molecular Immunology. 2006; 43: 1497-1507.

8. Filaci G, Bacilieri S, Fravega M, Monetti M, Contini P, Ghio M, et al. Impairment of CD8+T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol, 2001; 166: 6452-6457.

9. Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch. Pathol.Lab. Med. 2000; 124: 71-81.

10. Procedure for C3/C3c and C4/C4c quantitative determination. Dade Behring, Germany, 2005.

11. Hycor Biomedical Autostat TM-II anti-cardiolipin enzyme linked immunosorbent assay (ELISA). Hycor Bic Medic al Inc., USA, 2006.

12. Qian Yu Wei, Chungwen Eun-Hyung Lee F, et al. Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data”. Cytometry Part B: Clinical Cytometry, 2010; 78B- S69.

13. Loken MR. Immunofluorescence Techniques in Flow Cytometry and Sorting (2nd ed.). Wiley.1990: 341-353.

14. Ornatsky O, Bandura D, Baranov V, Nitz M, Winnik MA, Tanner S. Highly multiparametric analysis by mass cytometry. Journal of Immunological Methods. 2010; 361 (1-2): 1-20.

15. Liu C, Ahearn J. The search for Lupus Biomarkers. Best PractRes Clin Rheumatol. 2009; 23(4): 507-523.

16. Rivest C, Lew RA, Welsing PM, Sangha O, Wright EA. et al. Association between clinical factors, socioeconomic status, and organ damage in recent onset systemic lupus erythematosus. J Rheumatol. 2000; 27: 680-684.

17. Karamehić J, Subašić Đ, Gavrankapetanović F, Zečević L, Eminović I, Memić S, Šerić N, Drače Z. The incidence of antinuclear antibodies (ANA) detected by indirect immunofluorescence Assay (IFA method). Med Arh. 2007; 61 (1), 16-19.

18. Subašić Đ, Karamehić J, Ljuca F, Gavrankapetanović F, Delić-Šarac M, Eminović I, Kovačević D. Correlation of autoantibodies presence detected by IFA-anti ds DNA, IFA-AMA and immunoblotting with corresponding data in clinical management of autoimmune diseases. Bosnian Journal of Basic Medical Sciences. 2008; 8(1): 86-92.

19. Karamehic J, Subasic D, Kasumovic M, Hodzic H, Prljaca-Zecevici L, Tufekcic M, Aganovic-Musinovic I. Clinical management of patients with systemic lupus erythematosus (SLE) with different C1q-CIC and C3 concentrations. Med Arh. 2010; 64(2): 75-79.

20. Subašić Đ, Karamehić J, Gavrankapetanović F, Tvrtković E, Mekić M, Prljača-Zečević L, Muminagić S, Hasković E, Eminović I, Riđić O. Correlation of C3d effector molecules concentrations, C1q-CIC level and disease activity in patients with rheumatoid arthritis. Health Med, 2010; 4(4) supp-1; 1113-1119.

21. Mandel M, Gurevich M, Pauzner R, Kaminski N, Achiron A. Autoimmunity gene expression portrait: specific signature that intersects differentiates between multiple sclerosis and systemic lupus erythematosus. Cli Exp Immunol. 2004; 138: 164-170.

22. Krishnan S, Warke VG, Nambiar MP, Tsokos GC, Farber DL. The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells. J Immunol. 2003; 170: 4189-4194.

23. Nambiar MP, Mitchell JP, Ceruti RP, Malloy MA, Tsokos GC. Prevalence of T cell receptor zeta chain deficiency in systemic lupus erythematosus. Lupus. 2003; 12: 46-51.

24. Duriagin S, Ofori H, Jagodzinski PP. Flow cytometric analyzis of CD4+ T cell receptor zeta chain deficiency in patients with systemic lupus erythematosus. Adv In Med Sci. 2006; 51; 181-183.

25. Liu Z, Tugulea S, Cortesini R, Suciu-Foca N. Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8, CD28 T cells. Int Immunol. 1998; 10: 775-83.

Be the first to comment

Leave a Reply

Your email address will not be published.


Ova web-stranica koristi Akismet za zaštitu protiv spama. Saznajte kako se obrađuju podaci komentara.