Maria Hristova

Role of the Promoter Polymorphism IL-6 −174G/C in Dermatomyositis and Systemic Lupus Erythematosus

The promoter polymorphism −174G/C within the interleukin-6 gene (IL-6) has been reported to have a functional importance through the modulation of IL-6 gene expression in vitro and in vivo. IL-6 is thought to play an important role in autoimmune diseases and the effect of its receptor inhibitor—tocilizumab—has been recently studied. The aim of this case-control study was to investigate the association between the interleukin-6 −174G/C single nucleotide polymorphism and the susceptibility to dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients. Altogether, 87 patients—52 with SLE and 35 with DM—as well as 80 unrelated healthy controls were included in this study. All of them were analyzed by restriction fragment length polymorphism analysis (RFLP). The GG genotype and the G allele appeared to be associated with SLE, especially in women. None of the genotypes showed an association with DM. However, the G allele appeared to be associated with muscle weakness and it is a risk factor for elevated muscle enzymes. Our results indicate that IL-6 −174G/C polymorphism might be associated with the susceptibility to SLE especially in women. Although it is not associated with DM, it seems that IL-6 −174G/C polymorphism could modulate some clinical features in the autoimmune myopathies.

Association of TNF-α polymorphisms with adult dermatomyositis and systemic lupus erythematosus in Bulgarian patients

Background  Single‐nucleotide polymorphisms (SNPs) of tumor necrosis factor‐alpha (TNF‐α) have been implicated in various autoimmune diseases; however, the results are quite controversial, and there is still no widely accepted opinion about their role in the pathology of the autoimmune diseases. This is a pilot study to investigate the association of six SNPs of the TNF‐α gene with the risk of adult dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients.

Association of vitamin D receptor gene BsmI B/b and FokI F/f polymorphisms with adult dermatomyositis and systemic lupus erythematosus.

chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients. Psychooncology 2014; 23: 1103–1110. 3 Browall M, Gaston-Johansson F, Danielson E. Postmenopausal women with breast cancer: their experiences of the chemotherapy treatment period. Cancer Nurs 2006; 29: 34–42. 4 Komen MM, Smorenburg CH, van den Hurk CJ, et al. Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist 2013; 18: 885–891. 5 Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer 2000; 36: 766–771.

Diagnostic significance of anti-annexin-A5 antibody determination

Anti-annexin A5 antibodies are directed against annexin A5 — a phospholipid-binding protein that belongs to the ubiquitous annexin family. These antibodies were first discovered in 1994 by Matsuda et al. in women with recurrent fetal loss or preeclampsia and in patients with systemic lupus erythematosus and positive lupus anticoagulant and/or anticardiolipin antibodies. Since then anti-annexin A5 antibodies have been the focus of research. In addition to their well known prothrombotic and procoagulant activities the authors discuss the involvement of these antibodies in the pathogenesis of antiphospholipid syndrome, recurrent pregnancy loss, systemic lupus erythematosus and other immune and non-immune disorders. Controversial reports are presented and a possible interpretation of the results is given. The authors suggest the significance of anti-annexin A5 antibodies as an additional diagnostic marker and discuss the necessity of more extensive research on their clinical significance.

Monoclonal Antibody Drugs for Systemic Lupus Erythematosus.

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which engages most of the immune cells in its development. Various studies concerning the application of antibodies against TNF-α, BlyS, CD20, CD22, IL-6R and complement factors in treatment of SLE have been recently conducted and in spite of the good results reported by some of them, no definite conclusion on their risk-benefit profile can be drawn. The current review summarizes the results obtained in the field and reveals the perspectives for the development of new and more effective strategies for SLE treatment in combination with other immunomodulating drugs. Резюме Системная красная волчанка (СКВ) является гетерогенным аутоиммунным заболеванием, в патогенезе которого принимают участие разные иммунные механизмы. За последние годы накопилось достаточно большое количество данных о применении иммунных препаратов, содержащих антитела против TNF- α, BlyS, CD20, CD22, IL-6R и комплимента в лечении СКВ, в которых независимо от сообщаемых хороших результатов отсутствуют категорические данные об их эффективности и безопасности. Данное обозрение стремится обобщить результаты в этой области и поискать перспективы новых, более эффективных терапевтических стратегий в лечении данного заболевания в комбинации с другими иммуномодулирующими препаратами.

Association between estrogen receptor-α gene polymorphisms and dermatomyositis in Bulgarian patients

Immunol 2011; 128: 1352–1354. 7 Stzurz P, Adam Z, Hajek R, et al. Successful anakinra therapy in two patients with Schnizler syndrome. Onkologie 2011; 34: 265–268. 8 Carbone J, Paravisini A, Sarmento E, et al. Partial response to cyclosporine in a patient with Schnizler syndrome. Allergol Immunopathol (Madr) 2007; 35: 71–73. 9 Pascual-L opez M, Hern andez-N u~ nez A, S anchez-P erez J, et al. Schnizler syndrome with monoclonal IgG kappa gammopathy: good response to cyclosporine. J Eur Acad Dermatol Venereol 2002; 16: 267–270.

Genetically Determined TNF-α Secretion Influences the Development of Dermatomyositis and Systemic Lupus Erythematosus

Abstract Background: Abnormal secretion of TNF-α is known to play a role in the pathogenesis of dermatomyositis and systemic lupus erythematosus. Materials and methods: In the present study we have analyzed the concentrations of TNF-α in the sera of 30 patients with systemic lupus erythematosus (SLE), 28 with dermatomyositis (DM) and 30 healthy controls by standard ELISA tests. Results: We have found that -308A allele increases TNF-α secretion, while -1031C and -863A alleles decrease it. The -857C/T and 489G/A polymorphisms appeared in strong linkage disequilibrium (D’=0.93) but they did not seem to affect TNF-α secretion. Conclusion: TNF-α polymorphisms play a significant role in its secretion and influence the development of DM and SLE.

Blue toe syndrome as the initial manifestation of ANCA-associated vasculitis

The blue (or purple) toe syndrome describes the development of a blue or violaceous discoloration in one or more toes in the absence of obvious trauma, serious cold-induced injury or disorders producing generalized cyanosis. The presence of blue toe syndrome requires the clinician to search for primary systemic vasculitides, as well as for malignancy, underlying infection, thrombosis, cardiovascular pathology and other diseases. An accurate diagnosis is critical because many of the causes threaten life or limb, but the patient’s medical history, accompanying non-dermatologic findings on physical examination and the use of discriminatory laboratory tests are usually more important than the nature of the cutaneous abnormalities. We describe the case of a 53-year-old Caucasian male patient presenting with blue toe syndrome as the initial manifestation of ANCA-associated vasculitis.

IL-10 Single Nucleotide Polymorphisms and Lupus-Nephritis

ABSTRACT A pilot study was carried out to investigate the association of five single nucleotide polymorphisms of the IL-10 gene (-3575T/A, -2849G/A, -2763C/A, -1082G/A, -592C/A) with the risk of lupus-nephritis in Bulgarian female patients. We found a strong association between the -592 AA and CA genotypes (P = 0.009, OR 4.38, 95%CI 1.4–13.6) and the A allele (P = 0.037, OR 2.25, 95%CI 1–5) with the disease. Although statistically insignificant, the frequency of the IL-10 -3575TT, -2763CC, -2849GG and -1082GG genotypes was higher in the patients compared to the controls, which resulted in an increased odds ratio (OR). The haplotype analysis revealed an association between the IL-10 -3575T/-2849G/-2763C/-592A haplotype and lupus-nephritis (P = 0.04).