Ultrasonographic measurement of carotid artery resistive index and diastolic function of the heart in gout patients.

The aim of the study was to establish the functional disorder in the blood circulation of gout patients with a method that shows early damage of the heart and vascular structures. A total of 117 patients were examined cross-sectionally by a complex multimodal ultrasonography and were divided into four groups: 37 healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20 gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI) and parameters of the transmitral blood flow were determined: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In the examined ultrasonographic parameters between healthy controls and the three patient groups, there was a statistically significant difference (p < 0.001). Comparing asymptomatic hyperuricemia and gout without tophi, no significant difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p = 0.488) was found. Gouty tophi in comparison with gout without tophi and asymptomatic hyperuricemia had significantly lower Em (mean ± SD 0.07 ± 0.02 vs 0.09 ± 0.03 vs 0.13 ± 0.17) and significantly higher CCARI (mean ± SD 0.74 ± 0.05 vs 0.70 ± 0.05 vs 0.69 ± 0.05). Further multiple logistic regression revealed that tophi increased subject's likelihood of having category of CCARI ≥ 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07 (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the heart is independently associated with renal insufficiency. In terms of CV risk, tophi are an indicator of its increase.

Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus.

Genetic polymorphisms in cytokine genes, which influence gene expression, may have an important impact on SLE susceptibility and severity. The aim of this study was to examine the possible influence of two functional polymorphisms in cis-regulatory regions of IL12B gene in the susceptibility and clinical symptoms of SLE in Bulgarian patients. Female SLE patients (n = 141) and 124 healthy women were included in the study. Genotyping for the IL12B A/C polymorphism in 3'UTR was performed by restriction fragment length polymorphisms PCR assay and for the IL12Bpro polymorphism by allele-specific PCR. Genotype-22 of IL12Bpro polymorphism was overrepresented among women with SLE (28 vs. 17%; OR = 1.875; 95% CI: 1.037 ÷ 3.390; P = 0.037). Respectively, a higher frequency of allele-2 was found in patients than in controls (51% vs. 40%; OR = 1.566; 95% CI: 1.110 ÷ 2.210; P = 0.011). Also, we found significantly elevated frequency of genotype-22 of IL12Bpro polymorphism among SLE patients who were simultaneously carrier of genotype-AA of SNP in 3'UTR. Women with both homozygous genotypes, genotype-AA of SNP in 3'UTR and genotype-22 of IL12Bpro polymorphism, had a 2.1-fold significantly elevated risk for SLE development. The carrying of genotype-11 of IL12Bpro polymorphism was positively associated with hematological and neuropsychiatric manifestations of SLE. We have provided evidence that the IL12Bpro polymorphism was associated with SLE development among Bulgarian women. Although a strong individual effect of SNP in 3'UTR of IL12B was not detected, we found that genotype-22 of IL12Bpro was predominantly combined with genotype-AA of SNP in 3'UTR among SLE patients and this combination elevates the risk of SLE.

Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial.

OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE). METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry. RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration. CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.