Biomedical subjects

Piotr Adrian Klimiuk

Publications and source records attributed to Piotr Adrian Klimiuk.

14 recordsLinked to original sources

PubMed2006

The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis.

The objective of this study was to determine whether galactosylation of immunoglobulin G (IgG) in patients with rheumatoid arthritis (RA) correlates with severity and duration of illness. Serum IgG glycosylation from 50 patients with RA in comparison with 30 healthy controls was analyzed. IgG from sera was isolated and monosaccharide composition was determined by means of gas chromatography. Ratio of galactose to mannose content was calculated. Patients were divided into groups according to three different criteria: disease duration, severity of RA (disease activity score index), and radiological degree of advancement of illness according to Steinbrocker. In patients with RA, significant decrease (p<0,01) of galactose ratio was observed in comparison with healthy control. In patients with long duration of RA (more than 15 years), significant decrease of galactose (p<0.05) ratio in comparison with patients who have had arthritis for less then 5 years was observed. For the group of patients with severe RA, we found reduction of galactose (p<0.001) ratio vs the group of patients in remission. For those patients who had radiological stage IV according to Steinbrocker, IgG galactose (p<0.01) content per oligosaccharide chain were also more decreased than in those patients who had stage I RA. Decreased galactosylation and of IgG in RA was observed. The lack of this carbohydrate component of IgG correlates with severity and duration of RA and could be used in monitoring the progression in early arthritis.

Adult↗

PubMed2006

[Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the pathogenesis of rheumatoid arthritis].

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints characterized by the accumulation of mononuclear cells and the proliferation of the synovium-lining layer. The role of lymphocytes, macrophages and fibroblasts infiltrating the synovium is not fully understood. These cells are supposed to be involved in the tissue destruction by several mechanisms, including the production of proinflammatory cytokines and matrix metalloproteinases. Matrix metalloproteinases (MMPs) are the enzymes that participate in the proteolytic degradation and remodelling of the extracellular matrix. Their action is controlled by tissue inhibitors of metalloproteinases (TIMPs). In this review we describe the role of metalloproteinases and their tissue inhibitors in the pathogenesis of rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed2006

Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis.

OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. CONCLUSION: Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease.

Antirheumatic Agents↗

PubMed2005

A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with a wide range of extra-articular manifestations. Recent studies emphasise a key inflammatory role of the endothelial cells, either by overexpression of inflammatory mediators or by the proliferation of new blood vessels, in the disease process leading to the systemic organ involvement. To evaluate the relationship between internal organ manifestations and immunological markers of endothelial activation, serum levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were determined by an enzyme-linked immunosorbent assay in 64 RA patients and in 32 healthy controls. In comparison with a control group, higher serum concentrations of VEGF and ET-1 (p<0.001) in RA patients were demonstrated. A comparison between both RA groups with (20 patients) and without systemic involvement (44 patients) showed significantly higher concentrations of VEGF (p<0.05) and ET-1 (p<0.01) in the sera of patients with systemic manifestation. Moreover, a significant positive correlation between VEGF and ET-1 (r=0.475, p<0.001) in RA patients was found. A positive correlation between VEGF and Disease Activity Score (DAS) 28 index (r=0.39, p<0.005) as well as erythrocyte sedimentation rate (ESR) (r=0.564, p<0.0001) and C-reactive protein was found. ET-1 serum level correlated significantly with ESR (r=0.326, p<0.05) and DAS 28 index (r=0.307, p<0.05). These results suggest that the elevated serum levels of VEGF and ET-1 are associated with systemic organ involvement in RA patients and may play a key role in the pathogenesis of extra-articular manifestation of the disease.

Amyloidosis↗

PubMed2005

Histological patterns of synovitis and serum chemokines in patients with rheumatoid arthritis.

OBJECTIVE: Studies indicate the genetic, biological, and clinical heterogeneity of rheumatoid arthritis (RA). Recently the histological diversity of RA has been postulated. We investigated whether serum concentrations of interleukin 8 (IL-8), RANTES (regulated upon activation normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) are correlated with histological appearance of the rheumatoid synovitis. METHODS: Using ELISA we assessed IL-8, RANTES, and MCP-1 concentrations in serum of 47 patients with RA and 30 patients with osteoarthritis (OA). RESULTS: Morphological analysis of synovial specimens distinguished 2 types of rheumatoid synovitis. Twenty-eight RA samples presented diffuse infiltrates of mononuclear cells with no specific microanatomical organization and were categorized as diffuse synovitis. In the remaining 19 specimens, classified as follicular synovitis, formation of lymphocytic follicles with germinal center-like structures was observed. Serum levels of studied chemokines were increased in patients with RA compared to the OA control group (p < 0.001 for all comparisons). Concentrations of IL-8, RANTES, and MCP-1 were highest in serum of RA patients with follicular synovitis in comparison with patients with diffuse synovitis (p < 0.01, p < 0.01, and p < 0.05, respectively) and could distinguish RA patients with these 2 histological disease patterns. Serum levels of chemokines correlated with markers of disease activity such as erythrocyte sedimentation rate, C-reactive protein concentrations, and Disease Activity Score. CONCLUSION: Distinct histological variants of rheumatoid synovitis associated with different serum levels of IL-8, RANTES, and MCP-1 reflect clinical activity of the disease and confirm the concept of RA heterogeneity.

Adult↗

PubMed2005

[Defect of glycosylation of immunoglobulin G in rheumatoid arthritis patients].

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.

Arthritis, Rheumatoid↗

PubMed2005

[Immunopathological disturbances in systemic sclerosis].

Systemic sclerosis (SSc) is a disorder of the connective tissue characterized by the vascular dysfunction and progressive fibrosis of the skin, and various internal organs, which results in their dysfunction and failure. Activation of the immune system seems to play an important role in the pathogenesis of the disease. Contribution of the immune mechanisms to the development of the disease is indicated by the presence of the typical auto-antibodies, inflammatory cells infiltration in the skin and internal organs, and activation of cells participating in the immune response. Activation of the immune cells leads to release of proinflammatory/profibrotic cytokines and growth factors which in turn stimulate extensive proliferation of fibroblasts and collagen production. Activation of the immune system may also lead to impairment of endothelial function and development of angiopathy typical for systemic sclerosis, and subsequently chronic ischaemia of the affected tissues. In this review we describe the abnormalities of endothelial cells, T and B cells, and fibroblasts in patients with systemic sclerosis.

Autoantibodies↗

PubMed2005

[Correlations between serum matrix metalloproteinase (MMP-1, MMP-3, MMP-9, MMP-13) concentrations and markers of disease activity in early rheumatoid arthritis].

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.

Adult↗

PubMed2004

Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement.

Systemic sclerosis (SSc) is a chronic, multisystemic, autoimmune disease characterised by vascular changes and varying degrees of fibrosis of the skin and visceral organs. Organ systemic involvement in SSc is associated with an altered function of endothelial cells, perivascular infiltrating mononuclear cells and interstitial fibrosis. To evaluate the relationship between systemic manifestations and immunological markers of endothelial cell activation, serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were determined by an enzyme-linked immunosorbent assay in 31 SSc patients and in 30 healthy controls. In comparison with the control group, higher serum concentrations of sVCAM-1, sE-selectin, VEGF and ET-1 were detected in SSc patients (in all cases p<0.001). Elevated concentrations of sVCAM-1 (p<0.05), sE-selectin (p<0.05), VEGF (p<0.05) and ET-1 (p<0.01) dominated in the serum of SSc patients with organ systemic involvement compared to those without systemic manifestation of the disease. These results suggest that the serum levels of sVCAM-1, sE-selectin, VEGF and ET-1 may reflect the extent of internal organ involvement in SSc patients and point to a pathogenic role of these molecules in systemic manifestation of the disease.

Biomarkers↗

PubMed2004

Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis.

OBJECTIVE: Matrix metalloproteinases (MMP) are involved in the articular tissue destruction processes in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of multiple infusions of infliximab, a chimeric anti-tumor necrosis factor-a (anti-TNF-a) antibody, on concentrations of serum MMP and tissue inhibitors of metalloproteinases (TIMP) in patients with active RA. METHODS: Patients with RA were scheduled to receive 9 infusions of infliximab (3 mg/kg) at Weeks 0, 2, 6, and every 8 weeks thereafter. The therapy was combined with methotrexate (MTX) (7.5-20 mg/week). Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1, and TIMP-2 were measured by ELISA prior to infusion at Weeks 0, 2, 6, 14, 38, and 62. RESULTS: The initial infusion of infliximab downregulated serum levels of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p < 0.01), and TIMP-2 (p < 0.05). The second drug administration caused even more remarkable reduction of measured MMP (p < 0.001 in all cases) but not of TIMP levels. These changes were accompanied by decreased ratios of measured MMP to TIMP. Further infliximab therapy also significantly suppressed serum MMP levels, but was less effective. Before the first infliximab infusion serum concentrations of MMP and TIMP correlated with markers of RA activity such as the Disease Activity Score and C-reactive protein levels. After further drug administrations such associations, although less significant, were also noted. CONCLUSION: Anti-TNF-a antibody therapy combined with MTX resulted in rapid clinical improvement and reduced serum MMP concentrations in patients with RA. Further infusions of infliximab maintained the decrease of MMP, although to a lesser extent than the first and second doses.

Adult↗

PubMed2004

[Kidneys in rheumatoid arthritis].

Kidney pathology is a common phenomenon which is revealed in patients with rheumatoid arthritis (RA). Its incidence is estimated at 50-60% of all patients. It is an important clinical problem because it directly affects the outcomes of RA. Changes in the kidneys may result directly from either the underlying illness or complications due to various, including iatrogenic causes. In the following paper we present actual views on the subject of the known up-to-date causes of renal impairment in the course of RA.

Arthritis, Rheumatoid↗

PubMed2004

[Serum tumor necrosis factor alpha (TNF-alpha) concentration correlates with soluble adhesion molecules and vascular endothelial growth factor (VEGF) in rheumatoid arthritis].

In present study we investigated whether the serum concentration of tumour necrosis factor alpha (TNF-alpha) is associated with soluble adhesion molecules and vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA) patients. Serum levels of TNF-alpha, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble E-selectin (sE-selectin) and VEGF were assessed by ELISA in 38 patients with RA. We demonstrated the TNF-alpha to correlate with sICAM-1 (p < 0.001), sVCAM-1 (p < 0.01) and VEGF (p < 0.01). No association was noticed between TNF-alpha and sE-selectin serum concentrations. Moreover, serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels correlated with markers of RA activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. Data presented in this report support the concept of the VEGF synthesis stimulation by TNF-alpha. Analysis of the serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels may be useful in the prediction of the RA activity.

Adult↗

PubMed2004

[Therapeutic efficacy of peloid plasters in the treatment of osteoarthritis of the peripheral joints and spondylosis].

The objective of the study was to investigate the efficacy and tolerability of the peloid plasters in the group of 20 patients with osteoarthritis of peripheral joints (10 patients with gonarthrosis and 10 with omarthrosis) and 20 patients with spondylosis. This form of the pelotherapy decreased pain in joints after 10 days of the treatment. No allergic or other side effects were observed. Peloid plasters through the analgesic action improve the comfort of life and reduce the use of oral analgesic drugs.

Aged↗

PubMed2003

[Serum interleukin 6 (il-6A) concentration correlates with matrix metalloproteinases and their tissue inhibitors in rheumatoid arthritis].

We explored whether the serum concentration of interleukin 6 (IL-6) is associated with matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis (RA) patients. Serum levels of IL-6, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed with an ELISA technique in 30 RA patients. We observed the association between IL-6 and MMP-1 (p < 0.001), MMP-3 (p < 0.05), MMP-9 (p < 0.001), TIMP-1 (p < 0.01) and TIMP-2 (p < 0.05). Additionally, serum IL-6, measured MMPs and TIMP-1 correlated with the erythrocyte sedimentation rate, C reactive protein plasma level and the number of swollen joints. We suggest that assessing the serum IL-6, MMP-1, MMP-3, MMP-9 and TIMP-1 levels may be helpful in the prediction of the RA activity.

Anti-Inflammatory Agents, Non-Steroidal↗