Analysis for protein S100( marker associated with brain damage) - Causes, symptoms and treatment. MF.

Proteins of the S100 family( at present, at least 25 representatives are known: S100A1-S100A18, trichohylin, fillagrin, repetin, S100B, S100G, S100P, S100Z) - small dimeric calcium-binding proteins with a m.about 10.5 kDa, present only in vertebrates. S100 proteins constitute the largest subgroup of the so-called "EF-hand" calcium binding proteins( in the structure of the calcium binding site: helix E-loop-spiral F), to which, for example, also include calmodulin and troponin C. The name S100 was given at itsthe first description for solubility in 100% saturated ammonium sulfate. S100 proteins can form both homo- and heterodimers, in addition to Ca2 +, also bind Zn2 + and Cu2 +. The capture of ions changes the spatial organization of S100 protein and provides the possibility of binding to various proteins - their biological targets( more than 90 potential target proteins documented).

Representatives of S100 proteins show pronounced tissue-specific and cell-specific expression. They are involved in various processes - reduction, mobility, cell growth and differentiation, cell cycle progression, transcription, cell membrane organization and cytoskeleton dynamics, protection from oxidative cell damage, phosphorylation, secretion. It is assumed that S100 proteins perform both intracellular and extracellular functions, some S100 proteins are secreted and act similarly to cytokines. S100Β, which is produced primarily by astrocytes of the brain, is a marker for the activation of astroglia, mediating its effects through interaction with RAGE( receptor for advanced glycation end products - receptors for the final glycosylation products).It is shown that S100Β exhibits neurotrophic activity at physiological concentration and neurotoxic at a high concentration. Various forms of cancer manifest a pronounced change in the production of S100.Increased secretion of S100Β is characteristic of malignant melanoma. S100-RAGE interaction plays an important role in the association of inflammation and cancer, the survival of tumor cells and malignant progression. The clinical interest in S100 is associated with the use of it as a marker of brain damage in traumatic brain lesions, Alzheimer's disease( S100Β released from necrotic tissues can enhance neurodegeneration by S100-induced apoptosis), subarachnoid bleeding, strokes and other neurological disorders;in the monitoring of malignant melanoma, other neoplastic diseases, as well as inflammatory diseases.

The quantitative determination test S100( COBAS, Roche Elecsys 1010) is aimed at detecting the dimers S100A1B and S100BB.S100A1 and S100B( functional proteins can be represented by both homo- and heterodimers) are predominantly expressed by the central nervous system cells, mainly astroglia, but also produced in melanoma cells and, to some extent, in other tissues. The test can be used to monitor and control treatment, early detection of metastases and relapses( but not for diagnosis!) In patients with malignant melanoma and for a comprehensive assessment of the condition of patients with suspected brain damage.

Melanoma. S100 secretion is increased in patients suffering from malignant melanoma( especially in stages II, III and IV), the S100 level correlates with tumor progression, stage of the disease and can be used for prognosis, relapse and metastasis( not for primary diagnosis).Exceeding the threshold value of the test when monitoring the treatment of patients with melanoma can be expected, on average, in% - in patients without manifestations of the disease - in 5.5%;with regional metastases - 12.5%;metastases in the skin / distant lymph nodes - in 47,6%;distant / visceral metastases - in 42,9%( according to the results of the subsequent observation).In the control group of healthy people, the threshold is exceeded in 4.9%( confidence interval 95%).

If an elevated S100 level is detected, repeat testing is recommended to avoid false positive results and conduct appropriate tomographic studies to improve diagnostic accuracy.

Adult patients with potential brain damage. The S100 level grows in the cerebrospinal fluid and is released into the blood in various clinical situations. The measurement of S100 in neurological disorders is compared with the measurement of CRP in systemic inflammation. S100 can be detected in patients with brain damage of various origins, including traumatic injury or stroke.

After a stroke the growth of S100 begins during the first 8 hours, the increase persists for 72 hours, the concentration of S100 correlates with the volume of damage and the neurological consequences of the stroke. The increase in S100 after spontaneous of subarachnoid bleeding correlates with the severity of the pathology( a level above 0.3 μg / l is associated with adverse course). Traumatic brain injury is accompanied by an increase in the level of S100 in cerebrospinal fluid and serum.

Comparing the concentration of S100 with the results of tomography showed a high negative predictive value of the test( no damage due to tomography results with the negative result of S100) - 99-100%, but low positive predictive value( presence of brain injuries in the tomogram at S100 above the threshold) - 9- 13%.The sensitivity of the test is 96.5 - 100%, specificity is 30 - 35% with a confidence interval of 95%.With moderate traumatic brain damage, growth of S100A1B and S100BB can occur in 31% and 48% of patients without significant signs of cognitive impairment. The indicator can not be regarded as a reliable prediction of long-term neurological outcomes in such cases, especially in children.

The results should be interpreted cautiously, given the potential for changes in the integrity of the blood-brain barrier. The early release of S100 may be a consequence of mechanical excretion upon damage to the hematological barrier or activation of S100B expression when the brain is involved in a systemic inflammatory response. Potentially possible non-cerebral sources are S100B( chondrocytes, adipocytes).The growth of S100( > 1.5 μg / l) of after cardiac arrest and subsequent resuscitation of reflects a high risk of severe neurologic consequences.

S-100 is a specific protein of astrocyte glia, capable of binding calcium, with mole.weight 21 000 Yes. The protein was first identified in 1965 by B. W. Moore and got its name due to its solubility in 100% ammonium sulphate. It consists of two subunits - a and p. S-100( Pβ) is present in high concentrations in glial and Schwann cells( lemocytes), S-100( of) in glial cells, S-100( aa) in striated muscles, liver and kidneys. The protein is metabolized by the kidneys, its biological half-life is 2 hours. Astroglial cells are the most numerous cells in the brain tissue. They form a three-dimensional network, which is the supporting framework for neurons. Commercially available kits make it possible to determine the forms of the protein S-100( pp) and S-100( of), i. E.are suitable for diagnosis of brain tissue damage. In recent years, the definition of this protein has been increasingly used in the clinic as a marker of damage to the brain tissue in cases of cerebral circulation disorders. In patients with cerebral hemorrhage, the peak concentration of S-100 in the serum and CSF is observed already in the first day of the disease, with ischemic stroke this peak falls on the 3rd day. The level of increase in concentration correlates with the extent of brain damage. The serum level of S-100 in patients with ischemic stroke with a brain lesion volume of more than 5 cm3 was significantly higher than when the lesion volume was less than 5 cm3, and the protein concentration correlated with the severity of neurologic disorders. In ischemic stroke, the greatest increase in S-100 occurs in patients with cortical brain lesions. Subcortical lesions are accompanied by less significant increases in protein concentration in both serum and CSF.

Protein S-100 is released into the blood in patients operated under conditions of artificial circulation. Peak concentrations occur at the end of extracorporeal circulation and then decrease in uncomplicated cases. In patients with cerebral complications, the yield of protein continues in the postoperative period. The S-100 level of more than 0.5 μg / L 2 days after heart surgery indicates a patient's neurological complications.

S-100 - Marker of potential brain damage, a marker of malignant melanoma.

Test indications for protein S-100:

- Monitoring the flow and monitoring the success of
treatment of malignant melanoma, early detection of relapses and metastases.
- As an additional test in a complex of examinations with
potential brain damage( including traumatic
brain damage, stroke) for the overall assessment and prognosis of
neurological effects.

Protein S-100 norm

in blood serum is normally less than 0.105 - 0.2 μg / l;
in the cerebrospinal fluid is less than 5 μg / l.

Explanation of test results for S-100 protein:

Note: measurement of S100 concentration can vary considerably depending on the testing procedure, the results obtained by different methods can not be directly compared with each other, this can cause incorrect interpretation. If it is necessary to change the S100 testing procedure during the serial monitoring, the comparability of the results should be confirmed by parallel measurement by two methods.

Units of measure: μg / l.
Reference values: & lt;0.105 μg / l( 95% of healthy people without obvious manifestations of any pathology).

Increase in Protein S-100 in serum and CSF

The increase in protein S-100 in serum and cerebrospinal fluid( CSF) in cases of cerebral circulation disorders is due to the activation of microglia. In the early phase of cerebral infarction, microglial cells in the peri-infarction zone express the proteins of the S-100 family and actively proliferate, and the proteins are expressed no more than 3 days after the infarction. This suggests that activation of a constant population of microglia is an early response of brain tissue to ischemia and can be used as an early marker of its damage.

Increased values:

oncology: malignant melanoma( correlates with stage of the disease);

neurological disorders:

1. metabolic brain damage;
2. traumatic brain injury;
3. spontaneous subarachnoid hemorrhage;
4. Alzheimer's disease;
5. stroke;
6. multiple sclerosis( level fluctuations);
7. systemic lupus erythematosus( with neuropsychiatric involvement - organic brain syndrome, seizures, vascular incidents, psychosis);
8. hepatic encephalopathy;
9. bipolar disorder during exacerbations, but not during remission;
10. neurologic disorders after cardiac arrest and subsequent resuscitation;

physiological conditions: intensive physical training
S100 concentration measurement can vary considerably depending on the testing procedure, the results obtained by different methods can not be directly compared with each other, this can cause incorrect interpretation. If it is necessary to change the S100 testing procedure during the serial monitoring, the comparability of the results should be confirmed by parallel measurement by two methods.mcg / l. Reference values: & lt;0.105 μg / l( 95% of healthy people without obvious manifestations of any pathology).malignant melanoma( correlates with the stage of the disease);intensive physical training.