Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial

BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815

Development of a river ice jam by a combined heat loss and hydraulic model

International audienceThis paper discusses and shows the heat loss theory and the hydraulic theory for the analysis of the development of wide channel ice jams. The heat loss theory has been used in Iceland for a long time, while the hydraulic theory largely follows the classical ice-jam build-up theories used in known CFD models. The results are combined in a new method to calculate the maximum thickness and the extent of an ice jam. The results compare favorably to the HEC-RAS model for the development of a very large ice jam in Thjorsa River in Iceland. They are also in good agreement with historical data, collected where a hydroelectric dam project, Urridafoss, is being planned in the Thjorsa River

Anton Dolin as The Young Musician, Irina Baronova as The Beloved and artists of the company, in Symphonie fantastique, First movement, Covent Garden Russian Ballet, Australian tour, His Majesty's Theatre, Melbourne, April 1939 (1) [picture] /

From: Symphonie fantastique, an episode in the life of an artist : choreographic symphony / by Leonide Massine ; music and book by Hector Berlioz.; Inscription: "B1".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Choreography by Leonide Massine ; scenery and costumes by Christian Bernard ; scenery executed by Prince A. Schervachidze.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3963491. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldIn the present literature there is still controversy as to whether patients with systemic lupus erythematosus (SLE) are at increased risk of developing malignant diseases. In recent years a number of epidemiological studies have been conducted and some have suggested an association between SLE and malignant diseases while other studies have not. The objective of this study was to investigate this relationship in an unselected cohort of Icelandic patients with SLE. All patients diagnosed with SLE registered in the Icelandic SLE database were compared to the Icelandic cancer registry. For completeness, hospital charts and outpatient notes were also reviewed. The study period was from 1957 to the end of 2001. The O/E (observed/expected ratio), CI and P-value were calculated for total number of malignancies as well as individual malignancy types. Of 238 patients diagnosed with SLE (213 women and 25 men) 39 malignancies were diagnosed in 36 patients; 32 women and four men. Of the 36 patients, 27 were diagnosed subsequently with SLE and malignant disease. The mean age at diagnosis of SLE was 43.2 years (range 10-81) and at time of diagnosis of malignancy 62.7 years (range 43-86). The O/R for the whole study population was 1.38 (CI 0.89-1.87, P = 0.063), 1.45 for the women (CI 0.91-1.99, P = 0.051) and 1.03 for the men (CI 0.22-2.66, P = 0.560). The O/R for the most frequent malignancies diagnosed subsequently to SLE was 6.43 for squamous cell skin cancer (CI 1.31-18.5, P = 0.012), 5.48 for lymphoma (CI 0.64-19.6, P = 0.052), 2.46 for uterine cancer (CI 0.29-8.78, P = 0.196), 2.0 for ovarian cancer (CI 0.23-7.14, P = 0.264), 1.72 for lung cancer (CI 0.36-4.95, P = 0.254) and 1.6 for breast cancer (CI 0.65-3.23, P = 0.154). The total number of patient-years at risk was 2774 years. The results from this study on an unselected cohort of Icelandic SLE patients do not suggest an overall association between SLE and malignancy. Squamous cell skin cancer was the only individual cancer type that was statistically increased in the population and the numbers for lymphoma were borderline statistically significant

Characterization of a susceptibility locus for SLE, SLEB5, on chromosome 4p14-13.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSystemic lupus erythematosus is a systemic autoimmune disorder of unknown aetiology but is most likely caused by an interaction between several genetic factors and the environment. In a previously published genome scan we presented linkage to a marker on chromosome 4p13 in Icelandic families. Fine mapping of the region has been performed using 10 multicase families from Iceland and the maximum two-point LOD score was given by marker D4S2974 (Z = 3.57, alpha = 1). Multipoint analyses of the markers in the region suggest a putative disease gene to be located between markers D4S405 and D4S2381. The maximum multipoint LOD score (Z = 3.76) was given for marker D4S2974 in combination with the novel repeat GT4C2. A family-specific haplotype was segregating with the disease in each of eight families although a founder haplotype could not be identified. Analysis of recombination events in the patients delimited the susceptibility locus to approximately 3 cM. The susceptibility locus identified probably contains a mutation that has been enriched in the Icelandic population but is less common in other populations. We also show that this region is not identical to a susceptibility locus for SLE located on 4p16 where we detect no linkage

Association of three systemic lupus erythematosus susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin, with autoimmune manifestations in icelandic multicase systemic lupus erythematosus families.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To study autoimmune diseases and autoantibodies in Icelandic multicase systemic lupus erythematosus (SLE) families and to determine the association of 3 SLE susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin (MBL), with autoimmune disease in this population. METHODS: Eight SLE multicase families were studied, comprising a total of 124 family members (23 patients with SLE and 101 relatives). The diagnosis of an autoimmune disease was established and autoantibodies were measured in each family. In addition, PD-1.3A alleles were genotyped, and C4AQ0 allotypes were established by electrophoresis and haplotype analysis. Low levels of MBL were determined using enzyme-linked immunosorbent assay and variant-allele genotyping. RESULTS: In the SLE multicase families there was a high frequency of other autoimmune diseases (32.2%) and a high frequency of autoantibodies (53.2%). Of all family members, 59.7% were determined to have SLE, other autoimmune diseases, antinuclear antibodies, and/or other autoantibodies. The families showed genetic heterogeneity for PD-1.3A, C4AQ0, and low MBL levels; the frequency of each factor ranged from 0% to 85%. The frequencies of PD-1.3A and C4AQ0 were significantly increased in patients with SLE, relatives with other autoimmune diseases, and non-autoimmune disease relatives compared with controls. In the 7 families whose members had low levels of MBL, this factor was significantly associated with SLE, but the frequency of low MBL was decreased in relatives with other autoimmune diseases as compared with non-autoimmune disease relatives and controls. There were indications of an additive effect, and 91% of patients with SLE, 78% of relatives with other autoimmune diseases, and 75% of non-autoimmune disease relatives carried at least 1 of the 3 factors. CONCLUSION: These results demonstrate a high frequency of autoimmune diseases and autoantibodies in SLE multicase families. PD-1.3A and C4AQ0 are part of a predisposing genetic background. Other genetic and/or environmental factors are necessary for disease expression, demonstrated by a high frequency of PD-1.3A and C4AQ0 in non-autoimmune disease relatives. Low MBL levels may be one such contributing factor. The results of this study provide an example of epistatic genetic effects and overlapping genetics in autoimmune diseases