Subsets in psoriatic arthritis formed by cluster analysis.

The aim of the study was to create subgroups among psoriatic arthritis patients on the basis of dermatological features, clinical pattern of arthritis, and laboratory, immunological and radiological findings. Data on 100 patients were expressed in a standardised form and entered into hierarchical cluster analysis according to Ward's method. Seven subgroups were created. Fifty-six patients with mild psoriasis were sorted into a 'polyarticular group'. Two 'RA-like groups' were formed, differing from each other serologically and in axial involvement. In an 'oligoarticular group' (18 patients) serious skin disease and female gender predominancy were found to be characteristic. Eight patients with polyarticular arthritis were assigned to an 'erythrodermal group', in which polyarticular arthritis, mutilating, severe arthritis and a history of erythroderma were characteristic. Close to this group on the dendrogram eight women were sorted into a 'distal form'. Sausage fingers were frequent, and nail dystrophy was present in every case. In a 'pustular group' (three patients) the different type of skin involvement was considered and nail dystrophy was common. In the newly created subgroups not only the arthritic status, but also the type of the skin disease, played a determining role.

In vivo pulmonary toxicity of cellulose in rats.

Cellulose after a single intratracheal dose (15 mg per animal) brought about fibrosing granulomatous alveobronchiolitis and an increase of IgA production in the bronchoalveolar lavage. Fibrosing alveolitis showed moderate progression as a function of time. With different morphological methods, injury of type I pneumocytes and the incomplete repair of type II pneumocytes were detected. The damage of the alveolar epithelium initiated and activated a series of processes that led to definite pulmonary alterations: pulmonary fibrosis leading to the disintegration of the alveolo-capillary morphological functional unit.

A possible association of HLA-DR beta 1*04 subtypes and rheumatoid arthritis of peptide binding region amino acids.

HLA-DR beta 1*04 subtypes associated with rheumatoid arthritis (RA) were studied by polymerase chain reaction with sequence specific primers and the 86th amino acid of the DR beta 1 chain was analysed in RA patients vs healthy controls. The frequency of HLA-DR beta 1*0401 and 0404/0407 alleles was significantly increased in RA patients vs the controls, HLA-DR beta 1*0401 and 0404 being the dominant variants in RA. In most RA patients hydrophilic glycine proved to be the 86th amino acid of the peptide binding region thus it could have an effect on the development of RA.

[Low-dose methotrexate therapy of rheumatoid arthritis in the elderly]. / Kis dózisú methotrexat kezelés idöskori rheumatoid arthritisben.

Two years results of methotrexate treatment (13 patients, 7.5-10 mg weekly dose) in elderly onset rheumatoid arthritis are reported in comparison to other therapies (10 patients, im. gold 50 mg weekly or per os steroid max. 10 mg daily). Clinical activity of rheumatoid arthritis was measured with standard rheumatological parameters whereas progression of the disease was defined by means of a radiological method. Methotrexate caused better clinical improvement and retarded progression to a greater extent than the other therapies. Methotrexate achieved its maximum effect during the first 6 months of therapy. Methotrexate was well tolerable. Long term applicability of low dose methotrexate treatment in elderly age is emphasized.

Role of cellulose in wood dust-induced fibrosing alveo-bronchiolitis in rat.

Our experiments suggest that in the development of plant dust-induced fibrosing alveobronchiolitis--Scadding's fibrosing alveolitis--the cellulose content of plant dusts has a decisive aetiological role. Namely, the wood dust (pine) and the cellulose induced morphologically identical granulomatous inflammation and fibrosis, whereas the fibre-free extract of wood dust did not cause pathological changes in the lungs. The induction of H2O2 and superoxide anion production, shown in vitro in leucocytes, probably has an important role in the development of fibrosis.

High free and latent collagenase activity in psoriatic arthritis synovial fluids.

Collagenase activity has been studied intensively in SF from OA and RA patients. Less is known about collagenolytic activity in PsA SF. Therefore we examined collagenolytic activity in crude and trypsin treated SF as well as the alpha 1-antitrypsin and alpha 2-macroglobulin concentrations in 50 patients suffering from OA (n = 13), RA (n = 17), and PsA (n = 20). Free collagenolytic activity was low in the crude OA SF (1.80 +/- 1.35 micrograms released collagen/min/ml SF) and almost equally low in RA SF (2.35 +/- 1.80 micrograms released collagen/min/ml SF; P > 0.3). The PsA SF, however, exhibited a significantly higher free collagenolytic activity (5.63 +/- 5.69 micrograms released collagen/min/ml SF; P < 0.05 in comparison to OA and RA SF). The treatment of the SF with trypsin further activated collagenolytic activity in each group (OA 2.17 +/- 1.35 micrograms released collagen/min/ml SF; RA 6.48 +/- 6.73 micrograms released collagen/min/ml SF; PsA 11.24 +/- 5.02 micrograms released collagen/min/ml SF) and yielded significant differences between OA and RA, OA and PsA, and RA and PsA SF (P < 0.05). Concomitantly with the collagenolytic activity, the alpha 1-antitrypsin and alpha 2-macroglobulin concentrations of the SF were measured. In SF from patients with PsA (172.9 +/- 69.4 mg/100 ml) and RA (190.6 +/- 64.7 mg/100 ml) the alpha 1-antitrypsin was significantly higher than in those from OA SF (106.1 +/- 39.2 mg/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

[Serum keratan sulfate studies and their significance in the evaluation of cartilage degradation in degenerative and inflammatory joint diseases]. / Szérum keratán szulfát vizsgálatok és jelentöségük a porcdegradáció megítélésében degeneratív és gyulladásos ízületi betegségekben.

Fragments of high density cartilage proteoglycan (aggrecan) are released during either the normal or pathological turnover of cartilage proteoglycans, which fragments diffuse into the synovial fluids and then appear in the serum. The keratan sulphate (KS; a glycosaminoglycan side chain of aggrecan) is resistant to enzymatic degradation, it has a relatively low clearance and has a "standard" serum level indicating the actual level of cartilage (proteoglycan) breakdown. Using anti-KS monoclonal antibody in ELISA (enzyme-linked immunosorbent assay), we measured serum KS levels in patients with different joint diseases. The highest KS content (595 ng/ml) was measured in the sera of patients with articular chondrocalcinosis (calcium pyrophosphate crystal deposition disease/pseudogout). Slightly lower KS levels were determined in osteoarthrosis (OA; 578 ng/ml) and much less in rheumatoid arthritis (RA; 421 ng/ml). All these patient groups (either with degenerative or inflammatory joint diseases) expressed slightly higher KS levels compared to control blood donors (295 ng/ml). However, there were remarkable variations between these diseased groups, i. e., KS levels in patients with RA were significantly lower than in patients with OA (p < 0.001) and this difference was more pronounced in rheumatoid patients with I-II Steinbrocker stage (370 ng/ml) or in those treated with non-steroid anti-inflammatory drugs (NSAIDs) (382 ng/ml). Keratan sulphate levels in RA patients chronically treated with corticosteroid (460 ng/ml) or auro-thiomalat (473 ng/ml) indicate that these drugs may influence the cartilage metabolism more effectively than the NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine: an early messenger in inflammatory and immune reactions.

The local concentration of histamine at sites of inflammation and immune responses is invariably high. Recent studies suggest that the biological relevance of this accumulation of histamine extends beyond its well-characterized role in mediating allergic reactions. In this article, András Falus and Katherine Merétey describe a possible function for histamine in cytokine-governed regulation of inflammatory and immune cascades.

[Helicobacter pylori allergy]. / Helicobacter pylori allergia.

A case of a 44 year old woman with antrum gastritis and H. pylori infection was reported. After unsuccessful treatment of the disorder with bismuth and tinidazole, an auto-vaccine was prepared from the bacterium in order to eliminate the infection. After the first injection of the vaccine a generalised urticaria was observed. In the development of the skin eruptions a type I, and a type IV allergic reaction could be demonstrated using the H. pylori specific RAST-test and leukocyte migration inhibition respectively. After eradication of the bacterium by amoxycillin treatment, the clinical signs of both the gastrointestinal and allergic diseases disappeared.

Interleukin 6 levels in synovial fluids of patients with different arthritides: correlation with local IgM rheumatoid factor and systemic acute phase protein production.

Interleukin 6 (IL-6), a multifunctional cytokine particularly active in regulation of the acute phase response, governs the terminal maturation of B lymphocytes and participates in early activation of T cells. IL-6 levels of synovial fluids of 153 patients with different arthritides were measured by a simple sandwich enzyme immunoassay. Highest IL-6 concentrations were detected in patients with rheumatoid arthritis (RA), particularly in those characterized by very active general symptoms and severe joint pain. High IL-6 levels were detected in patients with juvenile RA with polyarticular onset of disease and in gout. Corresponding to the suggested in vivo relevance of IL-6, dose correlation of IL-6 levels with the synovial IgM rheumatoid factor accumulation was demonstrated. The rate of the correlation between synovial IL-6 level and concentration of serum C-reactive protein in RA was inversely proportional to the dose of steroid treatment in patients with RA.

Histamine influences the expression of the interleukin-6 receptor on human lymphoid, monocytoid and hepatoma cell lines.

Based on our earlier data on the enhancing effect of histamine on the action of interleukin-6 (IL-6), we have studied the molecular mechanisms of these interactions. The effect of histamine was investigated on the binding of 125I-IL-6 by B lymphoma cell line CESS, monocytoid cell line U937 and hepatoma cell line HepG2. Histamine increases the IL-6 binding by CESS cells and inhibits that by U937 and HepG2 cells. Using H1 receptor (cetirizin and loderix) and H2 receptor (cimetidine and ranitidine) specific antagonists, an H1-dependent stimulation of IL-6 binding by CESS cells was found. In contrast, down-regulation of IL-6 binding by histamine was clearly mediated through H2 receptors. On U937 cells, using a monoclonal antibody reacting with the 80 kd chain of the human IL-6 receptor, and H2-receptor mediated inhibition of IL-6 receptor expression was found by FACS analysis.

Complement C3 cleavage product in synovial fluids detected by immunofixation.

54 synovial fluids (SFs), 46 of them derived from various inflammatory diseases (30 rheumatoid arthritis (RA) SFs, 8 undefined arthritis (UA) SFs, 8 psoriatic arthritis (PSA) SFs) and 8 SFs from degenerative joint diseases (OA) were tested for C3c split product, using the immunofixation method. There were significant differences in the C3c product between the four groups investigated. In the OA group in the mean the percentage of C3c was low in comparison to the native C3 (C3c = 2.95%). RA SFs and UA SFs showed considerably higher values (20.1% for RA and 23.2% for UA) which were statistically significant in comparison to the OA SFs. With the exception of one SF the PSA SFs exhibited a relatively low percentage of the cleavage product. Despite the one high value the average C3c content of the PSA SFs was not statistically different from the OA SFs. In contrast to this low percentage of the C3c split product the PSA SFs showed the highest C3 concentration of all groups (87.0 +/- 36.5 mg/100 ml). Immunofixation is a simple and effective tool to determine the C3c split product in SFs. It might also be helpful for establishing the differential diagnosis of PSA vs RA on the basis of the C3 level of the SF in those patients where an elevated level of C3 is present.

Immunoglobulin profiles and antibacterial antibody levels in hairy cell leukaemia.

Serum immunoglobulin and natural antibody concentrations to environmental antigens have been determined in 26 hairy cell leukaemia (HCL) patients. The serum IgG, IgA and IgM levels as well as the concentration of antibodies to the majority of intestinal bacteria were found to be normal in both groups of HCL patients. In contrast to the data on the impaired humoral immunity of chronic lymphocytic leukaemia (CLL) patients, our results show that in HCL the studied aspects of humoral immunity are normal. Serum IgE levels were found to be significantly decreased in HCL when all patients were taken as a group. The difference was due to the decreased serum IgE concentration of splenectomized HCL patients, while IgE levels of untreated HCL patients did not differ statistically from that of the healthy controls.

Immunoglobulin profiles and antibacterial antibody levels in 50 patients a long time after posttraumatic splenectomy.

Serum immunoglobulin and antibacterial antibody concentrations have been determined in 50 patients 2 to 20 years after posttraumatic splenectomy. The serum levels of IgG, IgA and IgM were found to be significantly greater in the group of posttraumatic splenectomy patients than in that of the healthy controls. The serum IgE concentrations did not differ statistically from that of the controls. The serum level of natural antibodies against intestinal bacteria were found to be elevated (Shigella 1b, 2a, 3 and Salmonella typhi 02 strains) or normal (Salmonella typhi 0901 as well as E Coli 026 and 055 strains). Our results show that the studied functional aspects of humoral immunity in this group of otherwise healthy splenectomized individuals were not impaired.

Hormonal regulation of complement biosynthesis in human cell lines--II. Upregulation of the biosynthesis of complement components C3, factor B and C1 inhibitor by interleukin-6 and interleukin-1 in human hepatoma cell line.

The effect of interleukin (IL)-6 and IL-1 on the biosynthesis of complement components C3, factor B, C2, C4 and C1 inhibitor (C1 inh), as well as that of albumin, was studied in vitro in human hepatoma-derived cell line, HepG2. Measuring the amounts of secreted complement proteins we detected a significant upregulation of C3 by both hormones. The enhancement of the factor B and especially that of C1 inh production was predominant by IL-6. In our experimental system neither IL-1 nor IL-6 affected the biosynthesis of C2 and C4. Albumin secretion was significantly decreased only in the simultaneous presence of IL-1 and IL-6. Detection of the changes in the amounts of C3- and factor B-specific mRNA of HepG2 cells suggests a pretranslational regulation by these cytokines. The secretion of C3 and factor B was markedly potentiated when IL-1 and IL-6 were added together. However only the gene expression of factor B, but not of C3, was found to reveal synergism. IL-6 enhanced the in vitro production of C3 in mouse hepatocytes as well. This effect was greatly potentiated in the presence of histamine.

Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2.

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.

E. coli antibodies do not cause false-positivity in recombinant anti-HIV assays.

129 sera with known antibody titres against E. coli 026 and E. coli 055 strains were tested with the Abbot second generation anti-HTLV III recombinant screening assay. No difference in the O.D. values was found between sera with high, normal and low anti-E. coli titres. In addition, no false-positive reactions were observed with the anti-HIV negative sera containing E. coli antibodies in high titres in a Western blot assay in which recombinant env antigen was applied. These results suggest that E. coli assays in which E. coli-produced recombinant antigens are used.

Unequal expression of complement C4A and C4B genes in rheumatoid synovial cells, human monocytoid and hepatoma-derived cell lines.

C4A and C4B are closely related homologous complement proteins encoded in the class III region of major histocompatibility complex (MHC). The regulation of their expression is under genetic and hormonal control. In this study we investigated the synovial fluid plasma ratio of C4A and C4B of rheumatoid (RA) and osteoarthritis (OA) patients, and a predominance of the C4B gene expression by the synovial macrophages of RA patients was demonstrated. To clarify the tissue specificity of the expression of C4A and C4B genes, human monocytoid cell line U937 and hepatoma-derived HepG2 cells were studied. The gene expression of C4A and C4B were markedly different in these cells since a relative predominance of C4B mRNA in U937 cells and excess of that of C4A in HepG2 cells were detected. Recombinant interferon-gamma (IFN-gamma) up-regulated the expression of C4A gene in both cells, but had apparently no effect on the C4B gene. Our results demonstrate dissimilar expression patterns for the two human C4 genes, suggesting different tissue specific regulation of human C4A and C4B.

[Reactive arthritis following Chlamydia infection]. / Chlamydia fertözést követö reaktív arthritis.

The authors report on the clinical observation of 23 patients (5 women, 18 men) who suffered from seronegative spondylarthritis following chlamydia infection diagnosed clinically and serologically. Nine patients (2 women, 7 men) carried HLA B27 histocompatibility antigen. Sacroileitis confirmed by radiology was found in 16 cases. Genicular synovitis was the most frequent peripheral articular syndrome as well as Achilles tendinitis, "sausage-like" swelling of the finger and toes were observed and the ankle-, wrist-, elbow- and in a few cases the sternoclavicular and temporomandibular joint showed also involvement. Urological inflammation occurred in 9 cases, ophthalmological inflammation in 3 cases and pleuritis, pericarditis was observed in 1 patient. During the observation period 15 patients recovered upon Doxycyclin (Chinoin), Eryc (Biogal) non-steroid and occasional steroid therapy given 3 weeks long.

Stimulation of histamine receptors of human monocytoid and hepatoma-derived cell lines and mouse hepatocytes modulates the production of the complement components C3, C4, factor B, and C2.

The influence of histamine (and the related agonists and antagonists) alone or in the presence of recombinant human interleukin 1 alpha (IL-1 alpha) and gamma interferon (IFN-gamma) was studied on the production of complement components C3, C2, factor B, and C4 in vitro with human monocytoid cell line U937, hepatoma-derived cell line HepG2, and mouse hepatocytes. Both U937 and HepG2 cells responded to histamine through H1 and H2 histamine receptors. The effect of histamine on the biosynthesis and gene expression of complement proteins was predominantly enhancing via the H1 histamine receptors and inhibitory through the H2 receptors. The actual predominance of the histamine receptor involved (and the outcome of the ligand interaction) seemed to be greatly affected by the simultaneous activation of the cells by IL-1 or IFN-gamma.