Jozef Rovenský

Autoimmune thyroid disease and autoimmune rheumatic disorders: a two-sided analysis.

Chronic autoimmune thyroiditis (ATD) frequently overlaps with autoimmune rheumatic diseases. The aim of this study was to evaluate the prevalence of various non‐organ‐specific autoantibodies in patients with ATD, as well as the presence of ATD in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Subjects and Methods: Group 1 comprised 80 patients with ATD, and group 2 contained 80 patients with SLE or RA. A control group consisted of 34 healthy subjects. Group 1 was examined for the presence of non‐organ‐specific autoantibodies. Serum fT3, fT4, TSH, and antibodies against thyroglobulin, thyroperoxidase, as well as ultrasound of thyroid gland, were determined in group 2. Results: Patients with ATD had a significantly higher prevalence of antinuclear antibodies (ANA) than control subjects (45% vs. 14.7%, P < 0.001). There were no significant differences in the prevalence of other antibodies between the groups. ANA‐positive patients were younger than ANA‐negative ones and had significantly higher anti‐TG values (P < 0.05). The prevalence of ATD in group 2 was significantly higher than in the control subjects (24% vs. 8%, P < 0.05). No significant differences in the prevalence of ATD were detected between SLE and RA. Conclusion: The authors conclude that ANA is the most frequent non‐organ‐specific antibody associated with ATD, while the other antibodies occur rarely. The prevalence of ATD in SLE and RA patients was 24%. These results indicate that it is clinically important to screen patients with SLE and RA for the coexistence of thyroid autoimmune disease.

Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls

IntroductionBoth genetic and environmental factors contribute to rheumatoid arthritis (RA), a common and complex autoimmune disease. As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA. This study was initiated to investigate the association between defined genetic markers and RA in a Slovak population. In contrast to recent studies, we included intensively-characterized osteoarthritis (OA) patients as controls.MethodsWe used material of 520 RA and 303 OA samples in a case-control setting. Six SNPs were genotyped using TaqMan assays. HLA-DRB1 alleles were determined by employing site-specific polymerase chain reaction (PCR) amplification.ResultsNo statistically significant association of TRAF1/C5 SNPs rs3761847 and rs10818488 with RA was detected. However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220). The strongest signal was detected for HLA-DRB1*04 with an allelic P = 1.2*10-13 (OR = 2.92, 95% confidence interval (CI) = 2.18 – 3.91). Additionally, SNPs rs7574865STAT4(P = 9.2*10-6; OR = 1.71, 95% CI = 1.35 – 2.18) and rs2476601PTPN22(P = 9.5*10-4; OR = 1.67, 95% CI = 1.23 – 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (Pcorr = 0.114 and Pcorr = 0.180, respectively).ConclusionsIn our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA.

Arthropathy in Acromegaly

Articular involvement in acromegaly is one of the most frequent clinical complications and may be present as the earliest symptom in a significant proportion of patients. The involvement of other organs may be of clinical importance and contribute to increased morbidity and mortality of patients suffered from acromegaly. Early diagnosis and proper treatment of the diseases can prevent the development of irreversible complications of the disease and improve the quality of life in patients suffering from the disease.

The effects of β-glucan isolated from Pleurotus ostreatus on methotrexate treatment in rats with adjuvant arthritis

The purpose of this study was to evaluate the effect of β-(1,3/1,6)-d-glucan isolated from Pleurotus ostreatus (β-glucan-PO) on prophylactic treatment of adjuvant arthritis (AA) with methotrexate (MTX) in rats. Groups of rats with AA were treated with methotrexate (1xa0mg/kg/week), β-glucan-PO (1xa0mg/kg every second day) or their combination for the period of 28xa0days from adjuvant application. Body mass, hind paw swelling, arthrogram scores and a level of serum albumin were measured as markers of inflammation and arthritis. Treatment with low dose of MTX significantly inhibited the markers of both inflammation and arthritis. MTX and its combination with β-glucan-PO significantly increased body mass of arthritic rats. β-glucan-PO administered alone significantly decreased both the hind paw swelling and arthritic score. In combination with MTX, β-glucan-PO markedly potentiated the beneficial effects of MTX, which resulted in a more significant reduction of hind paw swelling and arthritic scores. The concentration of albumin in the serum of arthritic controls was significantly lower than in healthy controls. Both MTX alone and the combination treatment with MTXxa0+xa0β-glucan-PO significantly inhibited the decrease in serum albumin. β-Glucan-PO increased the treatment efficacy of basal treatment of AA with MTX.

Evidence for immunomodulatory properties of prolactin in selected in vitro and in vivo situations.

The relationship between neuroendocrine regulation and the immune system has recently become the subject of intense investigations. The pituitary secretes both immunostimulatory (growth hormone and prolactin) and immunosuppressive (ACTH) hormones, and is thus involved in the control of immune functions. The present work was aimed at the study of the immunoregulatory properties of prolactin in selected in vitro and in vivo model situations. Prolactin was found to enhance recovery of the receptor for sheep red blood cells (in vitro). Compared with control cells, incubation with prolactin and/or prolactin containing sera significantly enhanced the capacity of trypsin treated lymphocytes from the peripheral blood of healthy volunteers to form E-rosettes. Chlorpromazine stimulated prolactin release in males, and lactation stimulated prolactin release in females raised the number of large granular lymphocytes in peripheral circulation. Sera containing elevated prolactin levels stimulated the metabolic activity of peripheral neutrophilic leukocytes. These results suggest that prolactin may stimulate selective functions of cellular immunity, and that it is involved in interactions between the nervous, the hormonal and the immune systems.

Rheumatic diseases and Klinefelter's syndrome

The article summarizes reports on the concurrence of Klinefelters syndrome (KS) with inflammatory rheumatic diseases, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, the antiphospholipid syndrome, and ankylosing spondylitis. These include two case reports of patients with KS concurrently associated with RA or antisynthetase syndrome, respectively, previously reported by the author and his coworkers. Attention is paid to the pathogenesis and the course of the disease in patients with KS. The importance of early diagnosis of the syndrome, when occurring simultaneously with other diseases of connective tissue, is emphasized.

Treatment of rat adjuvant arthritis with flavonoid (Detralex®), methotrexate, and their combination.

In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a significant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. In this study treatment of adjuvant arthritis in rats with Detralex, methotrexate, and their combination were evaluated. Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, and whole‐body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. Long‐term prophylactic treatment with low‐dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis‐induced decrease of bone mineral density in AA rats was significantly lower only in the group treated with the combination of Detralex and methotrexate. Our results indicate that Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Glycoprofiling as a novel tool in serological assays of systemic sclerosis: a comparative study with three bioanalytical methods.

Systemic sclerosis (SSc) is an autoimmune disease seriously affecting patients quality of life. The heterogeneity of the disease also means that identification and subsequent validation of biomarkers of the disease is quite challenging. A fully validated single biomarker for diagnosis, prognosis, disease activity and assessment of response to therapy is not yet available. The main aim of this study was to apply an alternative assay protocol to the immunoassay-based analysis of this disease by employment of sialic acid recognizing lectin Sambucus nigra agglutinin (SNA) to glycoprofile serum samples. To our best knowledge this is the first study describing direct lectin-based glycoprofiling of serum SSc samples. Three different analytical methods for glycoprofiling of serum samples relying on application of lectins are compared here from a bioanalytical point of view including traditional ELISA-like lectin-based method (ELLA), novel fluorescent lectin microarrays and ultrasensitive impedimetric lectin biosensors. Results obtained by all three bioanalytical methods consistently showed differences in the level of sialic acid present on glycoproteins, when serum from healthy people was compared to the one from patients having SSc. Thus, analysis of sialic acid content in human serum could be of a diagnostic value for future detection of SSc, but further work is needed to enhance selectivity of assays for example by glycoprofiling of a fraction of human serum enriched in antibodies for individual diagnostics.

Apolipoprotein E polymorphism in patients with neuropsychiatric SLE

The aim of this study was to investigate a relationship between neuropsychiatric SLE (NPSLE), characterized by many different neurological and psychiatric disorders, and the polymorphism of apoE as a neurobiologically important molecule conferring increased risk and a worse prognosis of a variety of CNS diseases. One hundred and forty-six SLE patients and 93 healthy controls were studied. Out of the SLE cohort, 48 patients (32.8%) were diagnosed with NPSLE and further classified according to criteria of onset, extent, relapsing tendency and type of neuropsychiatric impairment. Apolipoprotein E (apoE) polymorphism was determined by PCR-RFLP and confirmed by isoelectrofocusing. The frequency of the ε4 allele was significantly higher in the NPSLE group than in the non-NPSLE group (17.7% vs. 3.1%, χ2=19.05, p<0.0001). Distribution of apoE genotypes was significantly different between NPSLE and non-NPSLE groups (χ2=80.95, p<0.0001). Both ε4 allele frequency (17.7% vs 8.6%, χ2=5.082, p<0.024) and genotype distribution (χ2=7.202, p<0.027) were significantly different between NPSLE group and the controls. The allele ε4 was also associated with earlier disease onset (Fisher’s test, p<0.036) and peripheral nervous system involvement (χ2=8.242, p<0.0041), but not with relapse frequency (p<0.37) or major/minor subtype of the disease (p<0.90). The ε4 allele carriers did not develop significantly more neuropsychiatric syndromes than non- carriers (1.75±0.23 sy (mean ± SD) in ε4 vs 1.85±0.19 sy (mean ± SD) in non-ε4 carriers, Mann–Whitney test, p<0.78). In conclusion, the data suggest an association between apoE polymorphism and NPSLE.

Hypothalamic-pituitary-adrenal axis in rheumatoid arthritis.

The controlled data accumulated so far support only subtle alterations in HPA axis function in RA, mainly at the adrenal level, and particularly in a subset of premenopausal-onset women. Such interpretation is supported by consistent findings of lower levels of adrenal androgens, particularly DHEAS, in premenopausal-onset RA patients. Consequences of the subtle HPA alterations in RA for the disease development remain unclear. From a broader perspective, the unresponsiveness of the HPA axis to chronic inflammation in RA simply can be seen as an ongoing adaptation to the disease state with higher priority to proper regulation of core body functions over the immune homeostasis.