Power Doppler sonography: synovial tissue assessment in RA.
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Publications and source records attributed to J K Lacki.
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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.
UNLABELLED: The aim of this study was to assess of bone mineral content (BMC) and bone mineral density (BMD) of the forearm using DXA technique (DTX-200) and to evaluate broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the heel using QUS technique (DTU-ONE). We examined 83 RA patients: 73 women and 10 men, at average age (55.0 +/- 12.2 yrs), ranging from 29 to 85 yrs. Average disease duration was 112.6 +/- 98.1 months. Disease activity was assessed according to Mallya and Mace index and radiological stage of the disease according to Steinbrocker index. We found significant correlation between BMC, BMD and BUA (r = 0.6572, r = 0.6081, respectively) and between BMC, BMD and SOS (r = 0.4704, r = 0.4723, respectively). IN CONCLUSION: quantitative ultrasound parameters (BUA and SOS) significant correlate with BMC and BMD values of the forearm assessed by DXA technique in rheumatoid arthritis patients.
Glucocorticosteroids have been recognized as a well known risk factor for drug induced osteoporosis. Many studies have shown a decrease in bone mass, bone quality disorders and an increase in the risk of fractures in patients with long-term corticosteroid therapy. Rheumatic patients, particular with rheumatoid arthritis, who are usually chronic steroid users are at the highest risk. On the other hand uncontrolled active inflammatory process is also a main factor for rapid bone loss. Some studies suggest that patients with low dose corticosteroid therapy (prednisone 5 to 7.5 mg per day) are not at increased risk of osteoporosis. Our study of 36 rheumatoid arthritis women treated with daily prednisone doses between 5 to 7.5 mg in comparison with non-steroid control group confirmed the above suggestion.
Rheumatoid arthritis (RA) is associated with HLA-DR4 and DR1 antigens. HLA-DRB1 gene sequences analysis demonstrated that only a limited set of alleles is positively associated with RA. Third hypervariable region sequences (70-74, 86) Q(R)R(K)RAA, G(V) are found in up to 95% of erosive RA. The presence of disease-associated allels may predict severe outcome of the disease. Therefore, their presence may allow us to start aggressive therapy in early stage of the disease.
Glycosylation is the main posttranslational modification of protein molecules. Human immunoglobulin G (IgG) is unique among serum glycoproteins because it is associated with at least 30 different biantennary oligosaccharide moieties. Elevated ratio of circulating IgG molecules lacking galactose from the oligosaccharides on the CH2 domain correlates with severity of the disease in a number of different autoimmune illnesses. Moreover, it may be helpful in differential diagnosis of rheumatoid arthritis (RA). By that we may try to predict outcome of RA. Its seems that agalactosyl IgG is distinctively connected with rheumatoid arthritis and may be involved in its immunopathogenesis.
We sought to investigate the influence of interleukin-10 (IL-10) and IL-6 on the acute phase proteins (APP) in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10, IL-6, Creactive protein (CRP), alpha-1-acid glycoprotein (AGP), and alpha1 antichymotrypsin (ACT) serum levels were determined in one hundred-eight patients (71 with SLE, 37 with RA). Quantification of the serum IL-10 level showed increased levels in SLE and RA patients as compared to healthy controls. Serum IL-6 level was found to be elevated in SLE and RA patients. A correlation between IL-10 and IL-6 serum level was found only in SLE. CRP and AGP serum levels were increased in RA as compared to controls, whereas in SLE only AGP was found elevated. A statistically significant correlation between IL-6 serum level and CRP, AGP and ACT was found only in RA. No correlation between IL-10 and serum level of CRP, AGP and ACT was established. Since IL-10 has a potent immunosuppressive activity, we expected it to be negatively correlated with APP levels. Surprisingly, IL-10 did not correlate with APP either in SLE or RA patients. However, the elevation of IL-10 serum levels in SLE and RA and the correlation between IL-10 and IL-6 in SLE may suggest that IL-10 may play a central role in inflammatory connective tissue diseases.
In the present study we investigated the long-term effect of intravenous pulse cyclophosphamide (CY) on lymphocyte surface antigens in systemic lupus erythematosus (SLE) patients. Blood samples derived from 17 lupus erythematosus patients were analysed using two- and three-colour flow cytometry. During the CY therapy, the total number of T lymphocytes (CD3+) was reduced by 31.4%, B lymphocytes (CD19+) by 67.4% and NK cells (CD16+) by 27.4%. Six months after the end of the CY regimen, these values recovered to entry levels. At the onset of the study we observed increased percentages of CD3+ CD25+, CD3+ CD4- CD8-, CD4+ CD29+, CD19+ and CD19+ CD5+ cells. The CY treatment regimen decreased the CD3+ CD25+, CD3+ CD4- CD8-, CD19+ and CD19+ CD5+ cells, but increased the CD3+ CD8+ subpopulation. Taken together, a deficiency of CD8+ T cells associated with CD4+ CD29+ predominance may imply an immune regulatory imbalance leading to abnormal CD4+ cell activation and in consequence to autoimmunity. Depletion of CD19+ cells combined with an enlargement of CD8 cells as a result of CY therapy may reduce the enhanced immune response in SLE patients.
In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha 1-antitrypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg/kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 +/- 0.73 U vs 0.37 +/- 0.13 U (control children), P < 0.001 and vs 0.23 +/- 0.12 U (control adults), P < 0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4%). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 +/- 0.24 U, 0.76 = 0.43 U, 0.95 +/- 0.52 U, respectively, P < 0.05). IgA values exceeding normal levels for age were found in 14% of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P < 0.01), alpha 1-acid-glycoprotein (r = 0.45, P < 0.01), alpha 1-antichymotrypsin (r = 0.52, P < 0.01), alpha 1-antitrypsin (r = 0.40, P < 0.01) and IgA (r = 0.56, P < 0.01) was established.
In order to determine the role of memory/naive T cells in atopic allergy patients we analyzed peripheral blood mononuclear cells before and during the grass pollen season. The study comprised 28 patients with seasonal symptoms of atopic allergy and 18 with perennial symptoms. Flow cytometry was employed to detect the expression of CD3, CD4, CD4CD45RA, CD4CD45RO, CD8, CD16, and CD19 molecules on peripheral blood lymphocytes. Allergic patients showed a decreased proportion of memory (CD4+CD45RO+) T cells compared with healthy subject (p < 0.05). The proportion of naive (CD4+CD45RA+) helper T cells did not differ between allergic patients and controls. The percentage of CD4+CD45RO+ cells increased during natural antigen exposure (grass pollen season) in allergic patients with seasonal symptoms. The results show at least two important observations. A potential homing tendency to nasal, bronchial and conjunctival mucosa of memory T cells (CD45RO) in atopic allergy patients may explain their deficiency in peripheral blood. Secondly, the grass pollen season may switch their phenotype from naive into memory T cells causing the increase of CD45RO cells. These events do not occur in non-allergic individuals and may thus constitute new insight into the basic mechanism of atopic allergy.
Synovial fluid samples from 21 rheumatoid arthritis patients were analyzed for lymphocyte subsets using flow cytometry and antibodies to the lymphocyte surface antigens CD3, CD4, CD8, CD16, CD19, CD29, and CD45RA. Synovial fluid levels of interleukin-6, rheumatoid factors and acute phase proteins were also measured. Depletion of CD45RA+ cells and predominance of CD29+ cells were found. Interleukin-6 levels were markedly elevated (1155 pg/ml; range, 24-3875 pg/ml), as were levels of IgM, IgG and IgA rheumatoid factors and of acute phase proteins. CD4 + CD29+ counts were significantly correlated with interleukin-6 levels. Interleukin-6 levels were significantly correlated with levels of all three rheumatoid factor classes but not with levels of acute phase proteins. Significant correlations were also found between CD19+ B counts and levels of all three rheumatoid factor classes. These data suggest that synovial fluid CD4 + CD29+ cells may be involved in the immune dysregulation characteristic of rheumatoid arthritis. The correlation between CD4 + CD29+ counts and interleukin-6 levels is consistent with the recent hypothesis that, together with monocytes, CD4 + CD29+ cells are an important source of the elevated levels of interleukin-6 seen in rheumatoid synovial fluid.
In order to get a better insight into cytokine network regulation in systemic lupus erythematosus (SLE), we analyzed levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the sera from 36 SLE patients. Moreover, C-reactive protein (CRP), alpha-1-acid-glycoprotein (AGP), and alpha-1-antichymotripsin (ACT) serum levels were evaluated. Serum levels of IL-10 and IL-6 were significantly increased when compared with healthy controls. TNF-alpha and IFN-gamma did not differ from normal values. We established the relationship between IL-10 and IL-6 as well as between IL-10 and TNF-alpha. None of the analyzed cytokines correlated with the acute phase protein levels. Based on the obtained data, we conclude that IL-10 may play the superior regulating role in SLE. A lack of correlation between the cytokines and acute phase proteins suggests their independence from cytokine regulation.
One hundred and fifty patients with rheumatoid arthritis (RA) were treated with immunosuppressive drugs for 12 months. Fifty nine patients were treated with methotrexate (MTX), 15 with cyclophosphamide (CTX), 30 with prednisone (PRE) and 46 with non steroidal antiinflammatory drugs (NSAID). The cell surface phenotype of lymphocyte was analyzed using immunofluorescence methods ans a variety of monoclonal antibodies. The studies were performed using fluorescence activated cell scanner (FACScan) and epifluorescence microscope. No changes in the percentage of CD3, CD4, CD8 were observed. However, in the MTX treated group the percentage of CD19+ (15.1% before treatment vs 10.2% after 12 months MTX treatment (p < 0.05) and CD5+CD19+ B-cells was decreased. In CTX treated group the percentage of both B cells (17.4% vs 11.0% (p < 0.5)) and activated T cells was decreased (CD25+: 2.8% vs 1.1%, p < 0.05 and HLA-DR+: 22.1% vs 12.7%, p < 0.01). Patients treated with prednisone expressed several changes in lymphocyte phenotype i.e. decreasing of activated T cells (CD3+CD25+: 6.9% vs 3.6%, p < 0.01), B cells (CD5+CD19+: 3.4% vs 0.8%, p < 0.001), and NK cells (CD16+: 14.8% vs 8.5, p < 0.01 and CD56+: 16.3% vs 10.7%, p < 0.01). Analyzing immunosuppressive drugs appeared to be very sufficient in the RA treatment. Moreover, the correlation between percentage of both B lymphocytes and activated T cells, and activity of disease were shown.
Ninety-six patients with refractory rheumatoid arthritis were treated with methotrexate for 48 months. We analyzed the effect of low doses of methotrexate (7.5-15 mg weekly) on the activity of the disease and on the progression in damage score. Clinical improvement was observed few weeks after the study was introduced. Following 48 months observation only 32 (33%) remained in the study. Seven of them needed additionally prednisone administration. In 64 (67%) patients the drug was withdrawn: in 18 (19%) due to the side effects, in 24 (25%) due to the lack of effectiveness, in 22 (23%) due to other reasons. Methotrexate did not affect the progression of damage score in our patients. Methotrexate appeared to be usefull drug in the treatment of rheumatoid arthritis, however clinical improvement was observed only during drug administration. After discontinuous of the therapy a flare of the disease was observed.
In the present study, in order to get a better insight into the mechanism of action of cyclophosphamide (CY) in rheumatoid arthritis (RA), we monitored the changes in lymphocytes' expression of leukocyte function associated antigen 1 (LFA-1). A group of 28 patients with refractory severe RA were treated with CY and methylprednisolone (MO) intravenously. Using flow cytometry we evaluated the changes in LFA-1 molecule expression on peripheral lymphocytes. In the analyzed group of patients the proportion of LFA-1 "dim" cells was reduced. After the treatment the ratio was partly normalized. Twelve months after cessation of the therapy high proportion of LFA-1 "dim" was observed only among CY/MP treated patients. The changes were related to clinical improvement. Based on the obtained data, it seems, that the treatment affecting the expression of LFA-1 may slow down lymphocyte migration and by that limit chronic inflammation within the synovium.
The aim of this study was to examine the lymphocyte phenotype in fibromyalgia (FB) patients. Nineteen patients [18 females, 1 male] who met the ACR classification criteria for FB were recruited into the study. The fluorescence of leukocytes was measured using Ortho Cytotron Absolute flow cytometer. Ortho-mune monoclonal antibodies [OK-Combo-Tests] were used for determination of the following antigens: CD3/CD19, CD3/HLA-DR, CD4/CD8, CD45RA/CD4. Serum IgE was established with ELISA [Merck, Germany]. There were no differences in percentage of CD3, CD19, CD4, CD8, CD3/HLA-DR and CD4/CD45RA cells as compared to healthy controls. We found a negative correlation between CD4 and CD8, CD3DR and IgE, CD8 and IgE concentration. The positive correlation between CD3 and CD3DR, CD3DR and CD8 was observed. The inhibitory effect of CD8+ cells subpopulation on B-cells and thereby on IgE production in patients afflicting for allergy has been already observed. Moreover, the symptoms to allergy has been found in about 50% of our patients. Taken together the data thus far obtained present a coexistence of symptoms of allergy and FB.
Immunoglobulin G-lacking galactose (Gal[0]) appears to be helpful in differential diagnosis of early synovitis, and correlates with disease activity in rheumatoid arthritis (RA). Its utility for RA monitoring and prognosis has been evaluated in the present study. Forty-eight patients with early RA were observed for 3 years. Hand radiographs were assessed according to Larsen and results were expressed as damage score (DS) and progression of damage score (PDS). Gal[0], DS, and PDS were evaluated at the onset of the study and after 1 and 3 years. The average values of Gal[0] in RA patients at the onset of the observation were significantly higher as compared to healthy controls (0.43 +/- 0.22 vs. -0.03 +/- 0.09, P < 0.05). The findings of Gal[0] after a 3-year follow-up were also higher as compared to healthy controls (0.37 +/- 0.21 vs. -0.03 +/- 0.09, P < 0.05). Radiological progression (PDS > 15) was observed in 16 patients. This group was characterized by a constantly high level of Gal[0]. The level of Gal[0] in patients without or with moderate radiological progression (PDS < 15) was significantly lower at the onset of the study and remained low during the observation. The relationship between Gal[0] and radiological progression was shown. The data thus far obtained suggest that Gal[0] may serve as an indicator for the disease course in patients with RA. Secondly, we cannot exclude the possibility that the constantly elevated level of Gal[0] causes erosions.
Since the enhanced production of IL-10 by human bronchogenic carcinoma has already been documented, in the present study serum levels of IL-10 were measured serially in patients with lung cancer undergoing radiotherapy. Thirty-one full diagnosed cancer patients underwent the radiotherapy procedures. The interleukin-10 (IL-10) and interleukin-6 (IL-6) serum levels were measured before therapy and after 3, 6 and 12 months after therapy. The interleukins concentrations were evaluated using a solid phase sandwich Enzyme-Linked-Immuno-Sorbent-Assay (ELISA). In all patients the serum levels of IL-10 have been found elevated. Due to the treatment they progressively declined to almost normal ranges in responders, while they remained elevated in non-responders. Serum levels of interleukin-6 have been elevated in the majority of our patients. After 12 months observation they also decreased, mainly in patients responding to the treatment. No correlation between serum IL-10 and IL-6 level has been found. The importance of serum IL-6 determination in lung cancer patients monitoring has already been established. The present study shows, that in spite of still unclear role of IL-10 in the process of carcinogenesis, it may be considered as a prognostic factor in lung cancer.