Circulating cytokines in Norwegian patients with psoriatic arthritis determined by a multiplex cytokine array system.

OBJECTIVES: Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with PsA and healthy individuals. METHODS: A novel protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 23 circulating cytokines of patients with PsA and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional inter-relationships among these pathological cytokines and identify biomarkers with prognostic and diagnostic utility. RESULTS: Univariate analysis demonstrated that serum levels of a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with PsA relative to unaffected controls including interleukin (IL)-10, IL-13, interferen (IFN)-alpha, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor [CCL3 macrophage inflammatory protein (MIP)-1alpha], CCL4 (MIP-1beta) and CCL11 (Eotaxin), while granulocyte-colony stimulating factor was significantly reduced in PsA patients. Correlational clustering was able to discriminate among, and hence subclassify, patients with varying levels of disease activity, which may prove useful in guiding therapy in these apparently phenotypically distinct disease subsets. DFA identified EGF, IFN-alpha, VEGF, CCL3 (MIP-1alpha) and IL-12p40 as analytes with the strongest discriminatory power among various PsA patients and controls. CONCLUSIONS: Our findings suggest that these factors modulate PsA pathology and the articular involvement in a synergistic manner. Identifying factors could be used in the development of clinical diagnostic tests, which are valuable to guide evidence-based diagnosis and disease management of PsA.

A longitudinal study of calprotectin in patients with polymyalgia rheumatica or temporal arteritis: relation to disease activity.

OBJECTIVE: Calprotectin is a granulocyte and monocyte cytosolic protein that is released during activation of these cells. The plasma level of calprotectin is raised in various inflammatory conditions and correlates with disease activity in a wide range of rheumatic diseases. We wanted to investigate whether calprotectin may be useful as a measure of disease activity in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: Forty-seven patients with PMR and/or TA were followed up to 3 years in a prospective longitudinal design. Plasma calprotectin was correlated with acute phase parameters, erythrocyte sedimentation rate (ESR), and peroral steroid usage before start of treatment and at four subsequent time intervals. RESULTS: Thirty-three patients had PMR, 10 had TA, and four had both diagnoses. Calprotectin was highly correlated with the acute phase parameters and ESR during the study period. Calprotectin was significantly decreased after start of treatment with oral prednisolone, and correlated with the daily dosage of prednisolone (r = 0.36, p < 0.01). CONCLUSION: Calprotectin plasma levels were significantly associated with acute phase parameters, ESR, and prednisolone usage in PMR and TA, indicating that calprotectin may be a good measure of disease activity in these conditions.

Sjögren's syndrome in an out-patient clinic: classification of patients according to the preliminary European criteria and the proposed modified European criteria.

OBJECTIVES: To investigate whether out-patients with a clinical diagnosis of Sjögren's syndrome (SS) satisfied current preliminary European criteria for SS, and to determine the proportion of patients who satisfied the proposed modified European criteria for SS and thus had indication of an autoimmune process. METHODS: Out-patients with a clinical diagnosis of SS registered between 1 January 1999 and 1 November 2000 were included in the study. RESULTS: Of 203 patients with a clinical diagnosis of SS, 116 (57.1%) satisfied the current European criteria and 83 (40.9%) satisfied the proposed modified criteria. CONCLUSIONS: Sicca symptoms and signs may have a variety of causes. In our study only 40.9% of the patients with a clinical diagnosis of SS satisfied the proposed modified European criteria and had evidence of SS as an autoimmune condition. Our findings indicate that for patient populations with an established diagnosis of SS according to the preliminary European criteria, approximately one-third will lose the diagnosis according to the modified criteria.

Clinical utility of diagnostic tests for rheumatoid factor.

OBJECTIVE: To investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF). METHODS: In a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology. RESULTS: Good agreement was found between the tests (kappa approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS. CONCLUSION: Although both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended.

Evaluation of diagnostic tests for antinuclear antibodies in rheumatological practice.

To investigate and compare the accuracy and usefulness of diagnostic tests for antinuclear antibodies (ANA) a cross-sectional study of sera derived from patients admitted to the Department of Rheumatology was tested for the presence of ANA using either indirect immunofluorescence on HEp-2 cells, indirect immunoperoxidase techniques on HEp-2 cells and mouse kidney, or two commercial enzyme-linked immunosorbent assays (ELISA). The diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of tests was compared using receiver-operating characteristics (ROC) methodology. All ANA-positive sera were further analysed for the presence of antibodies against extractable nuclear antigens (anti-ENA) and anti-DNA. A moderate to good agreement was found between tests, with kappa ranging from 0.469 to 0.659. Highest sensitivity for systemic lupus erythematosus (SLE; 93.3%) and primary Sjögren's syndrome (SS; 70%) was found using immunofluorescence on HEp-2 cells. Immunofluorescence on HEp-2 cells performed statistically better than the other tests in predicting SLE but not SS. All tests except mouse kidney showed good and comparable performance in detecting sera with anti-ENA and anti-DNA. At the given cut-off values indirect immunofluorescence on HEp-2 cells performed best. All assays except mouse kidney showed performance characteristics sufficient for use in routine analysis of ANA.

[The Chernobyl accident--did it influence the pregnancy outcome in Norway?]. / Tsjernobyl-ulykken--påvirket den svangerskapsutfall i Norge?

The outcome of pregnancies in the county of Sør-Trøndelag, in Norway, during the 27 months preceding and 21 months after the Chernobyl accident has been analysed on the basis of time of conception. The analysis showed a significant decrease in the number of conceptions during the three months immediately after the accident (April-June 1986). This finding can be interpreted to mean fewer "planned" conceptions. The Chernobyl accident did not seem to have had any impact on the proportion of conceptions ending as spontaneous abortions or ectopic pregnancies. There was a significant drop in the proportion of pregnancies ending as induced abortions during the year after the accident compared with the year before. However, due to some variation during this year it is difficult to draw any definite conclusions concerning the impact of the accident on induced abortions in this county. The proportion of pregnancies ending as births increased significantly during the year after the Chernobyl accident compared with the year before.