Acute phase response in rheumatoid arthritis patients treated with low doses of cyclosporin A.
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Acute-Phase Proteins↗
Biomedical subjects
M Sobieska
Publications and source records attributed to M Sobieska.
Microheterogeneity of alpha 1-acid glycoprotein in patients with rheumatoid arthritis.
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Adult↗
Microheterogeneity of alpha 1 acid glycoprotein in rheumatoid arthritis: dependent on disease duration?
The microheterogeneity of alpha 1 acid glycoprotein (AGP) was studied using affinity immunoelectrophoresis with concanavalin A (Con A) in serum samples of 43 patients with early rheumatoid arthritis (RA) without clinical features of intercurrent infection. The results were expressed as reactivity coefficients. Disease activity was measured by clinical (Lansbury's joint index, Mallya-Mace activity score) and laboratory (erythrocyte sedimentation rate, levels of soluble interleukin-2 receptor, C reactive protein, and AGP) indices. In contrast with previous reports, suggesting a decrease in AGP-Con A reactivity in patients with RA, high values of AGP reactivity coefficients were found in patients with disease of short duration, which were similar to those found in patients with acute bacterial infections. Conversely, normal or decreased values of AGP reactivity coefficients were found in patients with disease of longer duration. Regression analysis showed a significant relation between AGP reactivity coefficients and disease duration (multiplicative model). No other indices examined were significantly related to disease duration. These results, taken together with previous findings suggesting that cytokines control the glycosylation of acute phase proteins, indicate that differences in the microheterogeneity of AGP in early and longstanding RA reflect differences in cytokine action at different stages of the disease.
Adolescent↗
Glycosylation of acute phase proteins and interleukins following hip arthroplasty. Inflammation parameters studied in 10 patients.
We analyzed changes in glycosylation and serum concentrations of alpha 1-acid glycoprotein (AGP), antichymotrypsin (AC), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) following hip arthroplasty. Glycosylation of AGP and AC showed an increased reactivity to concanavalin A between postoperative Day 2 and Day 5 and Day 10, respectively. Serum levels of AGP and AC increased at the earliest on Day 5. The AC levels returned to baseline by Day 10. AGP, however, exhibited increased values beyond Day 14. CRP levels were elevated at Day 2 and remained increased beyond Day 14. sIL2R showed increased values at Days 5, 10 and 14. IL-6 was the first parameter to increase, and it returned to baseline in less than 5 days.
Acute-Phase Proteins↗
Microheterogeneity of alpha 1-acid glycoprotein in early and established rheumatoid arthritis.
OBJECTIVE: To determine whether factors related to disease activity determine changes in the glycosylation of alpha 1-acid glycoprotein (AGP) observed at the early stage of rheumatoid arthritis (RA). METHODS: Using affinoimmunoelectrophoresis with the lectin concanavalin A (Con-A), the microheterogeneity of serum AGP was studied in patients with early (n = 54) and established (n = 46) RA and the results were expressed as reactivity coefficients (AGP-RC). RESULTS: When compared with controls (n = 44), AGP-RC values were increased in the patients with very recent RA of no more than 3 months duration (p < 0.05), whereas normal or low AGP-Con-A reactivity was found in the patients with early RA with disease duration exceeding 3 months. In the entire group with early RA, the multiplicative model of regression described the relationship between AGP-Con-A reactivity and disease duration (p < 0.005). AGP variant with low binding affinity to Con-A predominated in the sera of patients with established RA and no relationship between the glycosylation profile of AGP and disease duration was observed in this group. When AGP-RC values were compared in the subgroups of patients with early and established RA with similar disease activity as measured by the Mallya-Mace score or erythrocyte sedimentation rate, there was a significant decrease in AGP-RC with increasing disease activity (p < 0.05). CONCLUSION: In view of our findings, early RA begins as an acute inflammation with increase of AGP-Con-A reactivity and becomes chronic during the first year of the disease. Factors related to disease activity appear important in determining the rate at which RA enters a chronic phase.
Adolescent↗
Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro.
The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
Acute-Phase Proteins↗
Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation.
Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.
Acute Disease↗
[Can thermal therapy of ankylosing spondylitis induce an activation of the disease?].
A randomized, open, controlled study was carried out in eight patients with spondylitis ankylosans, in a cross-over procedure including total body cryotherapy and whole spine paraffin mud packs. The effect of both therapies on clinical status and different laboratory data was investigated. No clinical changes were seen after either therapy; in contrast, in answering the spine function questionnaire patients reported an improvement after cryotherapy and a worsening after thermotherapy, but because of the small number of patients no positive conclusion was possible. The acute phase proteins (alpha-1-AGP, alpha-1-ACT, alpha-2-haptoglobin and alpha-2-coeruloplasmin) did not show any changes, only CRP increased after thermotherapy and declined after cryotherapy. Interesting changes were seen in the glycosylation profile of alpha-1-AGP: after thermotherapy an increase of bi-antennary oligosaccharides occurred, observed as appearance of a third peak in the affinity immunoelectrophoresis with con A and an increase of reactivity-coefficient of alpha-1 and glycoprotein which was also seen in the exacerbation of AS. This shows, that an activation of the inflammatory process may be possible by thermotherapy (perhaps because of an amplification of Il-6 production), but not by cryotherapy. Similar studies should be conducted in larger numbers of patients.
Acute-Phase Proteins↗
[Intraindividual comparison of whole body cold therapy and warm treatment with hot packs in generalized tendomyopathy].
In a cross-over study, the short-term efficacy of whole-body cold therapy and hot mud packs in patients with generalized tendomyopathy (fibromyalgia) was compared. As a pain assessment, visual analog scale and so-called pain score were measured; dolorimetry of the 24 tender points and eight control points was performed as well. Using these methods, we found that there is a significant improvement of all parameters examined during a 2-h period of measurements after cold application, and a marked improvement was also detectable 24 h after this therapy. In contrast, only pain score values showed a slight decrease immediately after hot mud-pack therapy, and no significant differences were found in visual analog scale and pressure tenderness as measured dolorimetrically. Central inhibition of nociceptors as a result of an activation of A-delta system as well as a blockade of gamma-motoneurons are discussed to be a mechanism of action of whole-body cold therapy, resulting in a decrease in muscle tonus. Long-term studies are needed to determine, if there is any enduring effect of whole-body cold therapy on pain in the patients with generalized tendomyopathy.
Cryotherapy↗
[Pressure point studies in generalized tendomyopathy (fibromyalgia) (comparison of various methods)].
There are different methods used for examination of tender-point pressure tenderness, which is one of the two most important criteria for diagnosis of generalised tendomypathy (fibromyalgia). When 11 of 18 tender points must be painful under the pressure of 4 kg for fulfilling the criteria of American College of Rheumatology (ACR), we require 12 of 24 points to be tender when pressed with a force less than 2 kg using dolorimeter. We have found that our method have a significantly higher specificity with about the same sensitivity, when compared with by ACR proposed method. Specificity and sensitivity depended on method used for pressure application and not on points examined. In view of our findings, we propose for scientific purposes dolorimetric measurement of pressure tenderness as being more reliable although more time-consuming method.
Adult↗
Immunological studies in patients with rheumatoid arthritis treated with methotrexate or cyclophosphamide.
One-hundred-and-two-patients (pts) with rheumatoid arthritis (RA) were observed for 12 months. Forty-eight pts were treated with a weekly low-dose of methotrexate (MTX), 23 pts with cyclophosphamide (CTX) (eight pts with one single intravenous dose, and 15 pts orally with a single daily dose), and 31 pts with nonsteroidal antiinflammatory drugs (NSAID) only. In all individuals acute phase response, i.e., C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) serum levels, and AGP microheterogeneity using affinoimmunoelectrophoresis with concanavalin A were evaluated. The phenotype of lymphocytes isolated from peripheral blood was characterized using immunofluorescence technique. Following treatment the increased level of CRP significantly decreased whereas AGP serum level remained unchanged. Among the patients, microheterogeneity of AGP expressed as reactivity coefficient (RC) was lower before treatment when compared with 17 controls (0.95 +/- 0.23 vs. 1.35 +/- 0.15, p < 0.01). After 12 months of MTX therapy AGP-RC rose significantly (1.19 +/- 0.13, p < 0.01). No changes were observed in AGP-RC levels in CTX and NSAID treated individuals. No significant differences were observed in the percentage of CD3+, CD4+, and CD8+ cells in all the patient groups, except in CTX intravenously treated patients. In this group of patients a decrease of CD4+ cells was noticed (60.1 +/- 11.5% and 43.8 +/- 12.5% before and after treatment respectively -p < 0.01). The percentage of CD19 positive cells decreased significantly during 12 months of treatment with MTX and CTX. The percentage of activated T cells (CD25+ cells and HLA-DR+ cells) remained unchanged in MTX treated patients and was reduced in both CTX groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Immune activation in endogenous depression].
Serum concentration of three positive acute phase proteins: C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1-antychymotrypsin (ACT) were measured in 81 patients with endogenous depression during acute episode and in 20 matched controls. Determination was also made of glycosylation types of AGP and ACT as well as of the concentration of interleukin-6 (IL-6) and its soluble receptor (sIL-6R). In patients with depression, the mean values of all parameters studied except for AGP glycosylation were significantly elevated compared with the group of control healthy persons, what may suggest an excessive immune activation in these patients in the form of acute phase response. Particularly intense were the indies of the immune activation in the subgroup of patients (1/3 of population studied) having pathologically elevated coefficient of AGP glycosylation (Type I glycosylation). Patients with Type I glycosylation had longer duration of illness and were characterized by recent depressive episode of greater severity and chronicity as well as refractoriness to pharmacological treatment. The results obtained corroborate the existence of excessive immune activation during acute depressive episode and suggest the possible role of this phenomenon in the pathogenesis and course of affective illnesses.
Adult↗