Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type IV, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy.

The present study was undertaken in order to investigate the relationship between tumor necrosis factor-alpha (TNF-alpha) gene polymorphism and the radiological progression of rheumatoid arthritis (RA) within the first 3-years of the disease. Sixty-eight RA patients (59 women and nine men) were observed for 3-years. TNF-alpha polymorphism analysis was performed in all patients. Radiographs of the hands were taken at the onset of study and after 3-years of follow-up. Radiographs were assessed according to the Larsen index (damage score and progression of damage score). We did not observe any correlation between TNF gene polymorphism and damage score or progression of damage score. The obtained data suggests that TNF-308 polymorphism cannot serve as an indicator of the disease course in RA patients.

The etiology of Graves ophthalmopathy (GO), representing the most common extrathyroidal manifestation of Graves disease, is multifactorial. Among multiple genetic, environmental, and endogenous factors, cytokines play a critical role in its etiopathogenesis. We studied an effect of glucocorticoid therapy on the serum IL-6, IL-4, and IL-13 levels in 18 GO patients. All the patients presented euthyroid GO with over 4 points according to the CAS classification (range 4-6; mean 4.94). The patients were treated with methylprednisolone (1 g every second day for three times) followed by 6 months oral prednisone (60 mg/day, with gradual reduction). The clinical examination (Clinical Activity Score and the GO severity by modified NOSPECS classification) and measurement of anti-TPO, anti-TG, anti-TSHR (TRAK), IL-6, IL-4, as well as IL-13 serum levels were performed before, after 2 weeks, and after 6 months of the glucocorticoid therapy. Significant serum IL-6 increases (p < 0.001) and moderate serum IL-4 and IL-13 increases (p < 0.05) were found in GO patients compared with healthy controls. After 2 weeks of the therapy, the serum IL-6 levels decreased in majority of the patients, however after 6-month observation, lower serum IL-6 levels were only in 8 patients who seemed to respond clinically to the therapy (mean value of the Clinical Activity Score decreased from 4.5 before the therapy initiation to 1.25 after 6 months of the glucocorticoid therapy). No changes in IL-4 and IL-13 serum levels during the therapy were observed. Statistical analysis revealed a good correlation between serum IL-6 level and the Clinical Activity Score (p < 0.01). Based on the obtained data, we conclude that IL-6 plays an important role in GO. It seems that IL-6 may serve as a useful factor in the inflammatory events of GO.

Rheumatoid arthritis (RA) is frequently complicated by peri-articular and generalized osteoporosis due to increased bone resorption by activated osteoclasts. Pro-inflammatory cytokines, such as TNF-alpha, interleukin 1 (IL1), and interleukin 6 (IL6) are thought, among other factors, to be directly responsible for this extra-articular complication of RA. Glucocorticoids (GCS) commonly prescribed in RA due to their strong anti-inflammatory effect are also well known for causing secondary osteoporosis during a prolonged use. An influence of low-dose GCS therapy (8.7 mg per day) on a bone turnover in female RA patients with or without previous history of GCS treatment was investigated by measuring bone mineral content (BMC), bone mineral density (BMD), and various biochemical markers of inflammation and bone metabolism in comparison to results obtained from: (1) RA patients who have not been treated with GCS and (2) the control group of healthy individuals. Sixty-two female patients with established active RA and 178 healthy individuals from the control group have been investigated. The RA patients were divided into three groups: 21 treated with GCS before the trial--these patients have continued GCS therapy using low doses during the observation; 21 with low-dose GCS therapy launched at the beginning of the trial; and 20 left without GCS treatment. All patients have been assessed twice: at the beginning and after 12 months of observation. BMC and BMD have been measured in all patients in a distal part of forearm. Additionally, several different biochemical markers of osteoporosis and inflammation have been determined. We did not notice any increase in bone metabolism between RA patients receiving GCS therapy for the first time and those treated without GCS after 12 months of observation. Results of BMC, BMD osteocalcin level, total and bone alkaline phosphatase, carboxy-terminal collagen cross links, carboxy-terminal propeptides of type 1 collagen, deoxypyridynoline, and calcium/creatinine ratio were comparable in both groups at the end of the study. There was a significant decrease of the level of IL-6 in patients who had GCS therapy launched at the beginning of observation (p<0.01). However, levels of C-reactive protein (CRP) and alpha1-acid-glycoprotein (AGP) have not changed; the level of ESR dropped significantly (p<0.05) in this group. In contrast, in the group of patients with the previous history of prolonged GCS treatment receiving low doses of GCS during the trial, statistically significant increase of CRP and AGP could be observed (p<0.05) along with further significant worsening of the primary low BMD (p<0.05). Based on the obtained data, we came to the conclusion that anti-inflammatory effect of the low-dose GCS therapy in RA patients without previous history of their use may balance their direct negative effect on BMC and BMD. In this group of RA patients, benefits resulting from the 12-month GCS therapy prevail over adverse effects, even if calcium with vitamin D3 supplementation, biphosphonians, or e...

We performed two-dimensional and Doppler echocardiography in 52 patients with systemic lupus erythematosus and in 34 healthy controls. In 25 patients (48.1%) echocardiographic disturbances were found (25/52 vs 2/34, p<0.001). Valvular abnormalities were detected in 18 patients (34.6%) but in only two controls (18/52 vs 2/34, p<0.01). The mitral valve was involved in 12 patients (23.1%). The most frequent finding was mild (13.5%) and moderate (9.6%) regurgitation or valvular thickening (9.6%). The aortic valve was involved in six and the tricuspid valve in three patients (11.5% and 5.8%, respectively). Only one patient had echocardiographic non-infective verrucous vegetation affecting the tricuspid valve. We did not observe significant hemodynamic valve disease. Endocardial findings were related to disease duration (p<0.05) but not to disease activity. Twenty-eight SLE patients (53.8%) had increased anticardiolipin antibodies (aCL). Patients with aCL (particularly those with IgG class) were characterized by a high incidence of echocardiographic abnormalities (p<0.001), mainly valvular (mitral or aortic) regurgitation (p<0.05). We found a relationship between anticardiolipin antibodies and disease activity (p<0.05). In conclusion, we postulate a prominent role for anticardiolipin antibodies in the pathogenesis of heart valve disease in patients with SLE.