[Show abstract][Hide abstract] ABSTRACT: In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.
Rheumatology International 09/2014; 35(4). DOI:10.1007/s00296-014-3112-1 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coexistence of rheumatic and neoplastic diseases may take different forms. Rheumatic paraneoplastic syndromes, including systemic sclerosis, scleroderma-like changes and Raynaud's phenomenon are induced by substances secreted by neoplastic cells and immunological disturbances connected are associated with malignancy. They may precede the clinical manifestation of neoplasm, occur simultaneously or after its diagnosis. In turn, chronic course of rheumatic diseases (Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) by immunologic stimulation may promote carcinogenesis. Genetic, environmental factors (viruses, chemical substances, radiation) and alterations of immunological surveillance may be the cause of both rheumatic and paraneoplastic disorders. Anticancer therapy may cause rheumatic diseases and immunosuppressive agents used in patients with rheumatic syndromes may have carcinogenic effect. Patients with long-standing or atypical course of rheumatic disorders, positive family or personal history of neoplastic disease, positive cancer markers, monoclonal antibodies or presence of other paraneoplastic syndromes should be diagnosed as possibly having occult neoplasm. In this paper we reviewed available literature on coexistence of rheumatic processes and malignancies to attract particular attention to practical aspects of this vital issue.
Polskie archiwum medycyny wewnȩtrznej 04/2008; 118(3):119-26. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis (SSc) is characterized by immunological disturbances, vascular damage and overproduction of extracellular matrix by stimulated fibroblasts. It has been postulated that immunological reactions involved in the pathogenesis of SSc may promote the development of malignancies. Coexistence of this disease with neoplasmatic processes is relatively frequent. In our report we describe a case a 54-year-old woman with scleroderma-like syndrome, which has preceded the occurrence of idiopathic myelofibrosis by many years. Owing to multiple repeated diagnostic tests we managed to diagnose this disease at the early stage, which enabled effective therapy with remission of blood dyscrasia as well as inhibition of skin lesions and lung fibrosis.
Polskie archiwum medycyny wewnȩtrznej 09/2007; 117(8):370-3. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our article we describe the case of 24 years old woman with overlap syndrome under form of systemic sclerosis and systemic lupus erythematosus complicated by secondary antiphospholipid syndrome (APS). The first manifestation of antiphospholipid syndrome was intrauterine fetal death. Afterwards pulmonary embolism occurred. After several weeks in result of catastrophic course of antiphospholipid syndrome coronary artery thrombosis and myocardial infarction occurred with following prominent left ventricle systolic failure and multi organ failure. The patient died about one month after discharge from the hospital.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 04/2006; 20(117):337-40.
[Show abstract][Hide abstract] ABSTRACT: Ankylosing spondylitis is ranked second among "great rheumatic diseases" which lead to considerable disability. The course of ankylosing spondylitis is chronic with variations in intensity of symptoms and is either continuously progressive or alternates with exacerbations and remissions. Difficulties in everyday life are due to limited motoric activity which makes full self-functioning rather impossible. The specificity of ankylosing spondylitis negatively affects the emotional state of patients. Patients are depressed, apathetic, discouraged to undertake treatment and rehabilitation. The aim of the present study was to assess the quality of life of patients with ankylosing spondylitis in four dimensions: physical, psychic, environmental and social; to determine the severity of anxiety and depression associated with the disease; and to analyze the quality of life and health. Diagnostic questionnaires were used in this study. Our study has shown that patients are unsatisfied with the quality of their health. In the course of the disease, physical and psychic symptoms exacerbate. Support and help are especially needed by persons living alone and by residents of villages. It seems that professional care, psychic support, education of the patient and of persons caring for him, and preparation to self-care are an integral part of therapy which may have an important effect in improving the quality of life.
Annales Academiae Medicae Stetinensis 02/2006; 52 Suppl 2:29-37.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to analyse the correlations between serum concentrations of the matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) and clinical markers of disease activity in patients with early rheumatoid arthritis (RA). The study group consisted of 30 RA patients, untreated with disease modifying antirheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. The analysis of serum concentrations of MMPs was based on a quantitative sandwich ELISA. We observed the positive significant correlations between studied MMPs and clinical markers of disease activity, such as number of swollen joints or erythrocyte sedimentation rate (ESR). Furthermore, we revealed significant correlations between serum MMP-1, MMP-3, MMP-9, MMP-13 concentrations and disease activity score (DAS) (p < 0.01; p < 0.001; p < 0.001; p < 0.05 respectively). We conclude that studied matrix metallo-proteinases might be useful clinical markers of disease activity in early rheumatoid arthritis.
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a multisystem disorder in which immunological abnormalities result in symmetrical joint inflammation, articular erosion, and extra-articular involvement. The etiology of RA is still unknown, but a defect in the glycosylation of IgG may be involved in its immunopathogenesis. Several studies have shown a correlation between the amount of IgG lacking galactose and the activity of RA. IgG galactosylation has been shown to be a useful marker of early RA and an indicator of poor prognosis. Analysis of IgG galactosylation may offer an insight into disease pathogenesis and may also be useful in RA diagnosis.
Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 02/2005; 59:485-9. · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
[Show abstract][Hide abstract] ABSTRACT: To determinate glycosylation of selected acute-phase glycoproteins (AGP, ACT, CP) and serum concentration of this proteins in Systemic Lupus Erythematosus (SLE) patients.
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.
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.
Configuration of analysis serum concentration and heterogeneity of acute-phase proteins is one of important diagnostic tests in SLE.
[Show abstract][Hide abstract] ABSTRACT: The concentration measurement of the acute phase proteins in blood serum has been applied in differential diagnosis of inflammatory arthritis since a long time. However, it appeared that the qualitative changes such as the presence of different glycoforms of the acute phase protein that was a glycoprotein, enabled to differentiate acute inflammatory conditions including the chronic ones, and to determine the dynamics of inflammatory process. This phenomenon is defined as a main heterogeneity, whereas the determination of the proportions of particular glycoforms is known as glycosylation profile. The changes of this profile are well known in the course of acute inflammatory conditions such as: bacterial sepsis, skin burns complicated with bacterial infections or acute pancreatitis. Considerably less observations concern the chronic conditions as: rheumatoid arthritis, systemic lupus erythematosus and degenerative joint disease. The examination encompassed 25 patients with rheumatoid arthritis, 21 with systemic lupus erythematosus, 19 with reactive arthritis and 21 patients with degenerative joint disease whose diagnosis was established on the basis of international diagnostic criteria. In all these patient the changes of C-reactive protein (CRP), acid glycoprotein (AGP) as well as glycosylation profile of the AGP were evaluated. For this purpose the electrophoresis method of two affinity directions with concanavalin A was applied, whereas the concentration of particular acute phase protein was determined by Laurell's immunoelectrophoresis method. The variants of glycoprotein resulted from electrophoresis were calculated with aid of planimetric method, and the results were presented as a coefficient of glycosylation. The characteristic patterns of glycosylation profile in the course of systemic lupus erythematosus, rheumatoid arthritis and reactive arthritis may be useful in differential diagnosis of the above mentioned diseases.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 11/2004; 17(100):349-52.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA).
The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62.
A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study.
Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.
[Show abstract][Hide abstract] ABSTRACT: 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.
Neurologia i neurochirurgia polska 34(6):1235-41. · 0.64 Impact Factor