Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p = 0.02 andp = 0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.

Провоспалительные цитокины интерлейкин-6 (IL-6), интерферон- (IFNg) и фактор некроза опухолей (TNF), известные как участники воспаления, играют важную роль в патогенезе рассеянного склероза. Исходя из опубликованных данных о влиянии полиморфизмов G(–308)A гена TNF, A(+874)T гена IFNG и G(–174)C гена IL-6 на продукцию этих цитокинов, мы изучали связь между полиморфизмом этих участков и развитием рассеянного склероза. Сцепление и ассоциацию аллелей указанных генов с рассеянным склерозом анализировали, используя тест неравновесной передачи аллелей (transmission disequilibrium test, TDT). В группе из 104 ядерных семей русской этнической принадлежности (больной и его здоровые родители) обнаружено, что аллель TNF*(–308)A чаще передается больным детям от здоровых гетерозиготных родителей (p = 0.01). Сцепления/ассоциации с рассеянным склерозом аллелей генов IFNG и IL-6 не выявлено. Таким образом, полученные данные свидетельствуют об участии гена TNF в развитии предрасположенности к рассеянному склерозу у русских.

Proinflammatory cytokines interleukin-6 (IL-6), interferon-γ (IFNg) and tumor necrosis factor (TNF) play an important role in the pathogenesis of multiple sclerosis. Based on the published data concerning the effects of the SNPs G(−308)A of TNF, A(+874)T of IFNG, and G(−174)C of IL-6 on the production of these cytokines, we investigated the relation of these polymorphisms with multiple sclerosis. Linkage and association of alleles of these genes with multiple sclerosis were analyzed by transmission disequilibrium test. In a group of 104 nuclear families of Russian ethnicity, the TNF*(−308)A allele was more frequently transmitted from healthy heterozygous parents to affected children (p = 0.01). Linkage/association of IFNG and IL-6 alleles with multiple sclerosis was not detected. Thus, the data obtained indicate that TNF is involved in susceptibility to multiple sclerosis in Russians.

Proinflammatory cytokines Interleukin-6 (IL-6), Interferon-gamma (IFNg) and Tumor necrosis factor (TNF) are known as participants of inflammation and play an important role in pathogenesis of multiple sclerosis (MS). Based on literature data about influence of SNPs G(-308)A of TNF gene, A(+874)T of IFNG gene and G(-174)C of IL-6 gene on production of these cytokines, we investigated association of these polymorphic sites with MS. Linkage and association of alleles of these genes with MS was analyzed by transmission disequilibrium test (TDT). In investigated group of 104 nuclear families of Russian ethnicity it was found that TNF* (-308)A allele transmitted from healthy heterozygous parents to affected children more frequently (p = 0.01). Linkage/association of IFNG and IL-6 alleles with MS was not revealed. Thus, data obtained indicate the participation of TNF gene in MS susceptibility in Russians.

Inflammatory demyelinating diseases in children and adolescents are sufficient problem of modern medicine. Its topicality is conditioned by as traditionally high prevalence of acute demyelinating conditions (acute disseminated encephalomyelitis) as increase of morbidity with chronic demyelinating forms of pathology (disseminated sclerosis) in children. The absence of clear diagnostic algorithm presents difficulties for the determination of tactics of treatment and prognosis on early stages of their development, e.g. at the time of maximal effectiveness of immunomodulatory medications. Besides, the list of medications for the prolonged immunomodulatory treatment of demyelinating diseases, registered in Russia, includes such drugs as interferon beta 1a for the subcutaneous injection, officially annotated for the use from 12-year old age.Key words: children, inflammatory demyelinating diseases, diagnostics, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6):139-145)

Immunomodulatory drugs reduce relapse rate and disease progression In relapslng-remlttlng multiple sclerosis but extensive data are not available on the effectiveness and tolerablllty of these drugs In childhood or adolescence. Interferon beta tolerablllty biased by frequency and method of drug administration. Drug administration has great Impact on treatment compliance and adherence. That's why we discuss moreover Interferon beta la Intramuscular as perspective Immunomodulatlve medication In pediatric MS cohort.

Inflammatory demyelinating diseases in children and adolescents are sufficient problem of modern medicine. Its topicality is conditioned by as traditionally high prevalence of acute demyelinating conditions (acute disseminated encephalomyelitis) as increase of morbidity with chronic demyelinating forms of pathology (disseminated sclerosis) in children. The absence of clear diagnostic algorithm presents difficulties for the determination of tactics of treatment and prognosis on early stages of their development, e.g. at the time of maximal effectiveness of immunomodulatory medications. Besides, the list of medications for the prolonged immunomodulatory treatment of demyelinating diseases, registered in Russia, includes such drugs as interferon beta 1a for the subcutaneous injection, officially annotated for the use from 12-year old age.

Immunomodulatory drugs reduce relapse rate and disease progression in relapsing-remitting multiple sclerosis but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. Interferon beta tolerability biased by frequency and method of drug administration. Drug administration has great impact on treatment compliance and adherence. That’s why we discuss moreover interferon beta 1a intramuscular as perspective immunomodulative medication in pediatric MS cohort.Key words: immunomodulatory drugs, interferon beta, multiple sclerosis, compliance, adherence, adolescence, childhood.

Symptomatic therapy of bladder hyporeflexia in patients with multiple sclerosis by intermittent catheterization in cases of insufficient efficacy of alpha-adrenoblockers allows to prevent bacterial infection complications and chronic renal failure and to achieve significant improvement of quality of life of such patients.

The onset of disseminated sclerosis occurs in childhood and juvenile age in 10% of patients. nevertheless, all immunomodulatory drugs for a treatment of this disease intended for adult population of patients, and there's an age limitation to the administration of these medications. There's only one interferon beta in group of «changing the clinical course of disseminated sclerosis medications», that was annotated to the administration in patients from 16 years. It's interferon betab1a (Rebif) for subcutaneous administration in 22 ?g and 44 ?g dosage. This drug was well known as an effective and safe medication for a long term administration for a long time in adult neurological practice. But doctors have to use interferon betab1a «off label» yet in patients younger 16 years in Russia and in other countries, comparing risk of changing the regimen of age limitation and risk of deprivation of un derbaged patient of years of qualitative life.Key words: children, disseminated sclerosis, interferon beta 1a, treatment.

The onset of disseminated sclerosis occurs in childhood and juvenile age in 10% of patients. nevertheless, all immunomodulatory drugs for a treatment of this disease intended for adult population of patients, and there's an age limitation to the administration of these medications. There's only one interferon beta in group of «changing the clinical course of disseminated sclerosis medications», that was annotated to the administration in patients from 16 years. It's interferon betab1a (Rebif) for subcutaneous administration in 22 ?g and 44 ?g dosage. This drug was well known as an effective and safe medication for a long term administration for a long time in adult neurological practice. But doctors have to use interferon betab1a «off label» yet in patients younger 16 years in Russia and in other countries, comparing risk of changing the regimen of age limitation and risk of deprivation of un derbaged patient of years of qualitative life. Key words: children, disseminated sclerosis, interferon beta 1a, treatment.