Vladimír Vašků

Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: increased prevalence of identified genotypes and of isolates with macrolide resistance.

ABSTRACT From January 2011 to December 2013, a total of 262 samples, from 188 patients suspected of having syphilis were tested for the presence of treponemal DNA by PCR amplification of five chromosomal loci, including the polA (TP0105), tmpC (TP0319), TP0136, TP0548, and 23S rRNA genes. Altogether, 146 samples from 103 patients were PCR positive for treponemal DNA. A set of 81 samples from 62 PCR-positive patients were typeable, and among them, nine different genotypes were identified. Compared to a previous study in the Czech Republic during 2004 to 2010, the number of genotypes detected among syphilis patients in a particular year increased to six in both 2012 and 2013, although they were not the same six. The proportion of macrolide-resistant clinical isolates in this 3-year study was 66.7%.

Paraneoplastic vasculitis and paraneoplastic vascular syndromes

Paraneoplastic syndromes are localized or diffuse pathologic manifestations that may occur in subjects affected by neoplastic diseases, even occult ones.

Genotype association of C(-735)T polymorphism in matrix metalloproteinase 2 gene with G(8002)A endothelin 1 gene with plaque psoriasis

Background: Excessive angiogenesis is one of the characteristic features of psoriasis. Objective: To determine the possible genetic background of neo-angiogenesis in plaque psoriasis, frequent polymorphisms in matrix metalloproteinase 2 (MMP-2) and endothelin 1 (ET-1) genes were studied. Methods: The case group (n = 119) included patients with plaque psoriasis, aged 44 ± 15 years. The age of onset of psoriasis was 27 ± 11 years. The control group (n = 184) consisted of healthy subjects without any individual history of psoriasis, aged 37 ± 15 years. C(-735)T MMP-2 and G(8002)A ET-1 polymorphisms were determined by PCR reaction with subsequent restriction analyses. Results: A significant difference in genotype distribution of C(-735)T MMP-2 between psoriatic and control patients was found (pcorr = 0.008). Two associated genotypes (CCGG and CTGG) of the two polymorphisms were significantly less frequent in psoriatic patients (pcorr = 0.03 and pcorr = 0.008, respectively). Conclusion: The results seem to reflect a different susceptibility of MMP-2 as well as of some associated MMP-2 and ET-1 genotypes to psoriasis.

Gene polymorphisms (G82S, 1704G/T, 2184A/G and 2245G/A) of the receptor of advanced glycation end products (RAGE) in plaque psoriasis.

Abstract. Having in mind the relationships among oxidative stress, psoriasis and common disorders, the association between polymorphisms in the gene encoding the receptor for advanced glycation end products (RAGE) and plaque psoriasis, including patients with a personal history of diabetes mellitus, cardiovascular disorders, cancer and allergy, was investigated. The allele frequencies and genotype distribution combinations of the four polymorphisms in the RAGE gene (6p21.3, G82S, 1704G/T, 2184A/G and 2245A/G) were compared in a case-control study of 272 subjects (130 patients with plaque psoriasis and 142 healthy control subjects of comparable age and sex distribution). The polymerase chain reaction with subsequent restriction analysis was used for detection of genotype variants. There was a significantly higher frequency of the 2184G allele of the 2184A/G RAGE polymorphism in psoriatic patients than in the control subjects (odds ratio 2.18, 95% CI 1.32–3.59, P=0.001). The 2184G allele occurred more often in psoriatic patients with a negative history of cardiovascular diseases (odds ratio 2.38, 95% CI 1.35–4.18, P=0.001, Pcorr=0.004), in those with a negative history of diabetes mellitus (odds ratio 2.05, 95% CI 0.1.22–3.45, P=0.004, Pcorr=0.012) and in those with a negative history of cancer (odds ratio 1.97, 95% CI 1.17–3.31, P=0.007, Pcorr=0.014) compared with the corresponding control subjects. We conclude that the 2184G allele of the RAGE gene is a significant risk factor for plaque psoriasis. The risk is associated with the non-presence of some common, especially cardiovascular, diseases in psoriatic patients.

Polymorphisms in inflammation genes (angiotensinogen, TAP1 and TNF-β) in psoriasis

Abstract This study focused on the association between plaque psoriasis and polymorphisms of several inflammation genes. Included in the study were 142 Caucasian (Czech) patients with plaque psoriasis and 141 healthy subjects. The genotypes of the polymorphisms in angiotensinogen [M235T ATG, A(-6)G ATG], in transporters associated with antigen processing TAP1 ( TAP1*0101, TAP*02011 and TAP1*0301 ) and in lymphotoxin α (TNFβ) (NcoI in intron 1) were detected by polymerase chain reaction-based methods and restriction enzyme analysis. An increase in B1 (less frequent) allele of NcoI TNFβ polymorphism was found in psoriatic patients compared to healthy individuals (odds ratio = 1.6, 95% confidence interval 1.13–2.26, P = 0.006). A positive family history of psoriasis was associated with a higher B1 allele frequency in NcoI TNFβ ( P = 0.011). Hardy-Weinberg disequilibrium was found in TAP1 polymorphism A→G at nucleotide 1207 in psoriatic patients. A case-control difference was found in the allelic concurrence of M235T and A(-6)G ATG polymorphisms. The most frequent population genotypes MMGG, MTAG and TTAA were observed in 92% of patients vs 74% of control subjects (odds ratio 0.29, 95% confidence interval 0.14–0.60, P = 0.0003). A positive history of tonsillitis and/or tonsillectomy was associated with a higher T allele frequency of the M235T ATG polymorphism ( P = 0.037) as well as with a higher G allele frequency of the A(-6)G ATG polymorphism ( P = 0.022). Polymorphisms in proinflammatory angiotensinogen and TNFβ genes were associated with plaque psoriasis, a positive family history of psoriasis and with frequent tonsillitis in childhood.

Three Retinoid X Receptor Gene Polymorphisms in Plaque Psoriasis and Psoriasis Guttata

Aim: Polymorphisms in retinoid X receptors (RXRs) are very interesting from the point of view of a possible association of their variability with psoriasis. Methods: A total of 293 patients with plaque psoriasis, 82 patients with psoriasis guttata and 202 control subjects were enrolled in this study focused on 3 polymorphisms in RXRA and RXRB gene associations. Results: A marginally significant increase in AA allelic frequency of the RXRA A39526AA polymorphism in plaque psoriatic men compared to healthy men was proved. In women with psoriasis guttata, the higher risk for genotypes AA and TT in the RXRB 3′+140A/T polymorphism compared to healthy women was identified (pcorr = 0.01). The genotypes A/A and AA/AA are more frequent in plaque psoriasis patients with a positive family history of psoriasis compared to the patients with a negative family history of psoriasis (pcorr = 0.02). The A/A genotype is more frequent in patients with plaque psoriasis and repeated tonsillitis/tonsillectomy (p = 0.02). In the RXRB polymorphism, no genotype TT is observed in patients with psoriasis guttata with a positive personal history of repeated tonsillitis (pcorr = 0.001). Conclusion: Individual gene characteristics of patients with psoriasis improve the possibilities of pharmacotherapy using pharmacogenomic approaches which could be further stratified in future according to the subtypes of psoriasis.

Multiple Myeloma Associated IgA Pemphigus: Treatment With Bortezomib- and Lenalidomide-Based Regimen

Generally, monoclonal immunoglobulins do not bind an autologous antigen, except for some cases, when it causes immune damage to body’s own tissues. Vesiculopustulous dermatitis associated with immunoglobulin (Ig) A deposition in the epidermis represents an autoimmune skin manifestation of monoclonal gammopathy. It is commonly referred to as subcorneal pustular dermatosis type of IgA pemphigus.1 In our previous work, we reported on complete and long-term remission of multiple myeloma associated IgA pemphigus after treatment with a bortezomib (Velcade) based regimen.2 In this work, to our knowledge, we are the first to publish a convincing clinical remission and excellent drug tolerance of a subsequent lenalidomide (Revlimid) based regimen used in the same patient for management of the relapsed disease.

Complete remission of multiple myeloma associated scleredema after bortezomib-based treatment

Scleredema is a rare scleroderma-like fi bromucinosis characterized by progressive thickening of the skin caused by excessive collagen and mucin depositions in the dermis. Various treatment regimens have been proposed, however with inconsistent outcomes. Herein we are the fi rst to report a complete dermatological and hematological remission in a patient with multiple myeloma associated scleredema after bortezomib-based chemotherapy.

Polymorphisms in angiotensinogen gene (M235T and G(-6)A) in multifactorial diseases

The aim of the study is to compare results of three association (case-control) studies in three multifactorial disorders (essential hypertension, atopic diseases and psoriasis) with two polymorphisms of angiotensinogen gene (M235T and A(-6)G). The diseases were chosen for their multigenic base and different immunological characteristic (Th1, Th2 and Thps) and angiotensinogen gene for its pleiotropic functional effects in general adaptive reactions. In all (control as well as case) groups, tight linkage disequilibrium between the polymorphisms was found. The strength of linkage (%) differed among the group. The direction of the linkage is identical in all groups (T is combined with A, M is combined with G). In hypertensive-normotensive study, only Hardy-Weinberg disequilibria were found, especially in men. No case-control differences were found for either single alleles or for allelic concurrence of both polymorphisms. In atopy-control study, marginal case-control differences in single allele distribution of both polymorphisms were found, but only in women. In psoriasis-control study, the only significant case-control difference was found,when genotypes MTAA and MTGG were present in 2/136 psoriatic patients vs. 20/142 control subjects (OR 0.1, 95% confidence interval 0.02-0.42, P=0.00015). The frequent polymorphisms in pleiotropic genes can form different formulae of genotype distribution in different multigenic diseases according to their contribution to the onset and/or progression of the disease in some evolutionary consequences.

Genetic predisposition for chronic venous insufficiency in several genes for matrix metalloproteinases (MMP‐2, MMP‐9, MMP‐12) and their inhibitor TIMP‐2

The project was scheduled as a case–control study to investigate the correlation between MMP‐2 (rs243864), MMP‐9 (3918242), MMP‐12 (rs7123600) and TIMP‐2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP‐2 genotypes and phenotypes of CVD.