**15. Conclusion**

214 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

important causes of AA established thus far can be presented as follows: (i) genetic predisposition and hereditary diseases affecting the molecular architectonics of connective tissue (e. g. Marfan's syndrome); (ii) atherosclerosis and arterial hypertension. Very often, AA is associated with atherosclerosis, especially, in patients of senior age groups. Male gender, smoking, carriage of specific infectious pathogens (herpes simplex virus, cytomegalovirus, *Chl. pneumonia*, syphilis and tuberculosis pathogens) also play a role in the pathogenesis of AA. Long duration of the *preclinical* stage (aortal dilation to the critical level) in patients with AA provides the physician with a unique opportunity to break the pathogenetic linkage and thus to arrest the further progression of the disease on going from the preclinical to the

It is more expedient to perform preclinical screening in three steps in full conformity with prenosological diagnostic protocols. *(i)* identification of blood serum levels of biomarkers in the form of so-called serodiagnostic packages (matrix metalloproteinases (MMP), cystatin *С*, osteoprotegerin (OPG), soluble fractions of elastin (SFE) and heavy chains of myosin (HCM), antibodies against *Ch. pneumonia*, CMV and HSV). These biomarkers are used as diagnostic package components and allow maximally accurate diagnosis and, which is no less important, estimation of lesion size even at the *preclinical* stage; *(ii)* MRT or contrasting CT scanning angiography for identifying exact location of dilated vessels, viz., *topological sites* in the vascular network responsible for hypersecretion of specific biomarkers; *(iii)* biopsy of the dilated portion of the aorta containing a suspected aneurism followed by morphological, immunogenetic and molecular-biological testing of bioptats. This procedure is highly invasive and its implementation is not recommended in the absence of positive results in the first two steps. If the dilated portion of the aorta cannot be visualized directly and the first-step tests give positive results, screening for biomarkers must be repeated after a period of several months. If positive results are obtained from serological doublet tests,

Early (*preclinical*) diagnosis holds especially great promise being the most efficient step in prophylactic and preventive treatment of AA. The uniqueness and high therapeutic potentials of *preclinical* diagnosis combined with low invasiveness of the nonsurgical approach and design, on its basis, of more advanced diagnostic protocols opens up fresh opportunities for the development of rationalized and practicable innovative technologies as a breakthrough in cardio- and angiosurgery. Prospective analysis of clinical utility of *targeted* therapy as a tool for *preventive* (preoperative) treatment and/or postsurgical

In considering the role of pathogenetic factors in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS), special emphasis should be laid on

According to GWA data, the contribution of MHC to RA risk can approximately be estimated as 30%, HLA-DRB1 alleles (e.g., DRB1\*0401 with OR of 3) being critical for RA. Additional loci essential for estimating RA risks were identified by high-density genotyping as HLA-DP in patients with anticyclic citrullinated peptide antibodies, (*HLA-DR2(DRB1\*1501))* and *DR3 (DRB1\*0301)* alleles in the MHC class II region with Ors of 2, risk variants in the MHC class III cluster encoding the TNF gene and the C2 complement

MRT or CT angiography must be conducted to the required extent.

angiorehabilitation will also make the subject of future investigations.

**14. Rheumatic diseases** 

components C4A and C4B.

risk genes and the extent to which they overlap.

clinical stage.

In-depth studies into pathogenesis and etiogenesis of autoimmune diseases and discovery of reliable biomarkers for diagnosing various pathological conditions provide a way for predicting, with a sufficiently high degree of probability, the risk of relapses and exacerbations and possible clinical manifestations of the disease. In its turn, considerable recent progress in medical science (in medical genetics, bionanomedicine and bioinformatics, in particular) provides a clue to the design of advanced protocols for preclinical screening of patients. The construction of individual genetic maps with special reference to familial predispositions and time-lapse monitoring of risk groups for pathomorphological markers have one common goal, viz., to collect information for early implementation of preventive and therapeutic intervention strategies. Moreover, dynamic control over functional activities of different body organs and tissues on the basis of well established and validated proteomic and metabolomic data enables early prediction of exacerbations and complications and implementation of preventive therapy. The latter is based on the use of state-of-art pharmacological protocols and, if surgical correction is required, of the most recent advances in transplantation and regenerative medicine.

Considerable improvement and wide-scale application of preclinical diagnosis algorithms and preventive treatment protocols for routine clinical application are among the most topical problems in today's medical practice. More urgent strategies are aimed at compensating structural and functional deficiencies of damaged organs and fragments thereof. In genetic studies combined with early detection of minor lesion foci and analysis of immune, proteomic and metabolomic disturbances open up new vistas for social welfare with the ultimate goal to improve current standards of public health care at large.
