Effect of etanercept on serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor in patients with rheumatoid arthritis.

OBJECTIVE: Endothelium and adhesion molecules are engaged in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyse the effect of etanercept on the levels of soluble cell adhesion molecules (sCAMs) and vascular endothelial growth factor (VEGF) in patients with active RA. METHODS: Patients were receiving 50 mg/week of subcutaneous etanercept and 10-25 mg/week of methotrexate (MTX). Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 18 RA patients (prior to injection) at 0, 3, 6, 9, and 12 months. RESULTS: A decrease in serum levels of sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01), and VEGF (p<0.001) was observed in RA patients after 3 months of treatment with etanercept. Six months of therapy with etanercept prolonged the suppression of serum sICAM-1 (p<0.01) and even more remarkably diminished sVCAM-1, sE-selectin, and VEGF (in all cases p<0.001) concentrations as compared to baseline (month 0). Treatment also effectively diminished sICAM-1, sVCAM-1, and VEGF levels at months 9 and 12 (in all cases p<0.001), and less significantly sE-selectin (p<0.05 at month 9 and p<0.01 at month 12). The Disease Activity Score including a 28-joint count (DAS28) measured at 3, 6, 9, and 12 months decreased significantly compared to baseline (in all cases p<0.001). CONCLUSION: Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFalpha) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.

Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis.

OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62. RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.

The prevalence and clinical significance of antiphospholipid antibodies in the patients with systemic sclerosis--preliminary report.

PURPOSE: The aim of our study was to evaluate the prevalence of anticardiolipin and anti-beta2-glikoprotein I (anti-beta2GPI) antibodies in patients with systemic sclerosis (SSc) and to correlate the presence of these antibodies with clinical and serological features of the disease. MATERIAL AND METHODS: 22 patients (21 women and 1 man) fulfilling the ACR classification criteria of SSc were included into the study. In all SSc patients a detailed clinical evaluation including skin and internal organ involvement was performed. Moreover, the measurements of antitopoisomerase I (anti-Scl-70) and anticentromere (ACA) antibodies were done in all patients studied. Anticardiolipin antibodies in IgM and IgG class and anti-beta2GPI antibodies in IgM, IgG and IgA class were evaluated using ELISA kits (Hycor Biomedical and DiaSorin). RESULTS: Anticardiolipin antibodies were found in 10/22 (45.5%) patients with SSc, in 6/12 (50%) with diffuse SSc and in 4/10 (40%) with the limited SSc. Anticardiolipin antibodies in the IgG class were observed in 4/22 (18.2%) patients, and in the IgM class in 9/22 (40.9%) subjects. Anti-beta2GPI antibodies were found in 9/22 patients (40.9%), of which 3/22 (13.6%) had antibodies in IgG class, 4/22 (18.2%) in IgM class and 3/22 (13.6%) in the IgA class. Anti-beta2GPI antibodies were found exclusively in the patients in whom the anticardiolipin antibodies were also present. An association between the presence of antiphospholipid antibodies and internal organ involvement (pulmonary fibrosis, pulmonary hypertension and the alterations of oesophageal function) was not significant. No significant correlation was found between the presence of anticardiolipin or anti-beta2GPI antibodies and the presence of anti-Scl-70 or ACA antibodies. CONCLUSIONS: The results of our study indicate that the prevalence of anticardiolipin antibodies and anti-beta2GPI antibodies is relatively high in patients with SSc. A more detailed assessment of the relationship between the presence of antiphospholipid antibodies and the clinical and serological features of SSc requires further studies on the larger group of patients and a several years of follow-up.

Concentration and microheterogeneity of acute-phase glycoproteins in patients with systemic lupus erythematosus.

PURPOSE: To determinate glycosylation of selected acute-phase glycoproteins (AGP, ACT, CP) and serum concentration of this proteins in Systemic Lupus Erythematosus (SLE) patients. PATIENTS AND METHODS: The study was carried out on 35 patients with active SLE and 15 healthy volunteers. The immunological measurements were performed at first day of hospitalisation, before receiving treatment. The concentration of CRP, AGP, ACT and CP were evaluated by electroimmunoassay using anti-AGP, anti-ACT, anti-CP antibodies. CRP levels were determined by radial immunodiffusion with anti-CRP antibodies. The microheterogeneity of the acute phase proteins was assessed by agarose affinity electrophoresis using Con A as a ligand, as was described by Bøg-Hansen. RESULTS: Between SLE patients and control group statistically significant differences (p < 0.01) were observed in serum concentration of all investigated parameters. There were no significant differences in serum acute-phase proteins levels with regards to patient's age, sex and disease activity. The reactivity coefficients: AGP-RC, ACT-RC, CP-RC in SLE patients were similar to the healthy group. The precipitate curves were similar in both groups. The main difference was in the area of the precipitant, which was bigger in the SLE patients. CONCLUSIONS: Configuration of analysis serum concentration and heterogeneity of acute-phase proteins is one of important diagnostic tests in SLE.

Kidney crisis in systemic sclerosis.

Renal crisis in systemic sclerosis occurs in the group of patients with rapid and aggressive course of the disease, often after several years of the ailment and with the diffuse form. Scleroderma renal crisis (SRC) is most frequently characterized by malignant hypertension, renal insufficiency, and less often by the symptoms of microangiopathic hemolytic anemia. Renal crisis symptoms appear suddenly and are not usually preceded by significant prodromal symptoms. SRC is always life-threatening and requires specific treatment with drugs blocking angiotensin-converting enzyme. Early diagnosis and introducing appropriate treatment give a patient a chance to survive SRC episode and improve his prognosis. SRC is of great importance to clinicians as it still causes high mortality rate. Chronic and subacute renal crisis is connected with a small risk of acute renal failure. However, it gradually leads to a substantial dysfunction of this organ. Thus, a useful examination in the diagnostics of chronic renal crisis is checking the vascular flow in renal cortex and evaluating intrarenal resistance.

The occurrence of pulmonary hypertension in patients with systemic sclerosis hospitalized in the Department of Rheumatology and Internal Diseases Medical University of Bialystok in years 2003-2004.

Pulmonary hypertension (PH) is one the most fatal complications of systemic sclerosis (SSc). The aim of the present study was to investigate the occurrence of PH in SSc patients hospitalized in Department of Rheumatology and Internal Diseases University Hospital of Bialystok in years 2003-2004. PH was defined as pulmonary artery systolic pressure (PASP) higher than 35 mmHg as evaluated by ECHO-Doppler. We found PH in 23 out of 53 (43%) SSc patients included in the study. In the majority of patients 20/23 (87%) PH coexisted with the presence of scleroderma lung disease as evaluated by high resolution computed tomography of the lungs. In the remaining 3/23 (13%) patients isolated (arterial) PH was detected. Patients with isolated PH tend to have higher values of PASP (82 +/- 39.0 mmHg) than those with PH and interstitial lung disease (42.5 +/- 6.4 mmHg). The results of our study indicate that PH is a frequent complication of SSc.

[Guillain-Barré syndrome in a patient with primary sicca syndrome]. / Ciezki zespól Guillain-Barré u chorej z pierwotnym zespolem suchosci.

At the age of 23 the patient showed the first signs of dryness syndrome. Those symptoms developed progressively and during a few years primary Sjögren syndrome was noted. In the 37th year of life suddenly the patient developed very severe Gullian-Barré syndrome with involvement of the peripheral and central nervous system and with a considerable autonomic component. After treatment the patient improved, however mild symptoms of central and peripheral nervous system destruction remained. Those symptoms are still present and the patient is under the care of the Neurology and Rheumatology Clinic.