Monitoring of Disease Biomarkers Activity and Immunophenotyping as Important Factors in SLE Clinical Management

Abstract

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, because 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.

Systemic Lupus Erythematosus (SLE) Responder Index response is associated with global benefit for patients with SLE

“…Serum concentrations of anti-dsDNA, C3, and C4 are key serological markers that correlate with disease activity in SLE. 33,34 We observed a trend that SRI(4) response was associated with a reduction in anti-dsDNA. However, no differences in changes from baseline in C3 and C4 complement concentrations between responders and nonresponders were observed.…”

Phenotypic analysis of peripheral B cell populations during Mycobacterium tuberculosis infection and disease

“…Immuno-phenotyping has proven to be a very useful tool in the identification, monitoring and management of various clinical diseases [ 9 – 11 ]. Although recent publications have sought to develop in depth multicolour flow cytometric panels for the accurate delineation of various lymphocyte populations and subpopulations (including B cells) during immunodeficiencies [ 12 , 13 ], very few studies exist that specifically assess immune-phenotypic change during active Mycobacterium tuberculosis infection [ 7 , 14 ].…”

Flow Cytometry as Platform for Biomarker Discovery and Clinical Validation

“…Subasic et al (2012) showed that the number of TCR molecules on the T-cell surface of SLE patients is lower than normal condition, and otherwise for these receptors CD molecules make specific connection. SLE phenotypes are characterized by double CD negativity (CD3 +/À , CD4 À ) caused by an abnormal level of IL-2 and IL-17.…”