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- Asarnoj, A., et al.
(författare)
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IgE to peanut allergen components : relation to peanut symptoms and pollen sensitization in 8-year-olds
- 2010
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:9, s. 1189-1195
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.
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- Knitza, J, et al.
(författare)
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Toward Earlier Diagnosis Using Combined eHealth Tools in Rheumatology: The Joint Pain Assessment Scoring Tool (JPAST) Project
- 2020
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Ingår i: JMIR mHealth and uHealth. - : JMIR Publications Inc.. - 2291-5222. ; 8:5, s. e17507-
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Tidskriftsartikel (refereegranskat)abstract
- Outcomes of patients with inflammatory rheumatic diseases have significantly improved over the last three decades, mainly due to therapeutic innovations, more timely treatment, and a recognition of the need to monitor response to treatment and to titrate treatments accordingly. Diagnostic delay remains a major challenge for all stakeholders. The combination of electronic health (eHealth) and serologic and genetic markers holds great promise to improve the current management of patients with inflammatory rheumatic diseases by speeding up access to appropriate care. The Joint Pain Assessment Scoring Tool (JPAST) project, funded by the European Union (EU) European Institute of Innovation and Technology (EIT) Health program, is a unique European project aiming to enable and accelerate personalized precision medicine for early treatment in rheumatology, ultimately also enabling prevention. The aim of the project is to facilitate these goals while at the same time, reducing cost for society and patients.
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- Mathsson Alm, Linda, et al.
(författare)
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The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis : a systematic review and meta-analysis
- 2018
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 36:1, s. 144-152
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Forskningsöversikt (refereegranskat)abstract
- Objective. We assessed the ability of anti-cyclic citrullinated peptide (CCP) tests to diagnose rheumatoid arthritis (RA), comparing the effect of manufacturer assay type, study design (single-and two-gated) and duration of disease (early vs. established). Methods. We searched seven data-bases for relevant diagnostic studies containing data on CCP tests in known or suspected RA patients. We used a bi-variate model to produce summary estimates for test sensitivity, specificity, and positive and negative likelihood ratios. Summary Receiver Operating Characteristic (sROC) curves were derived to compare early versus established RA. Results. 83 studies were identified and included. For individual manufacturer tests there was considerable variation in both pooled sensitivity (range 67-83%) and specificity (range 90-96%) estimates. This heterogeneity was also observed when grouping studies into two-gated and single-gated designs. Study design and disease duration impacted on sensitivity, with single-gated study designs and early RA patients resulting in lower estimates than two-gated and established disease, respectively. Conclusion. This review highlights the large number of CCP tests that are now commercially available and the considerable variation in their diagnostic performance. This variation, although partly influenced in this analysis by the study design (single-gated vs. two-gated), seems to have different levels of impact depending on the manufacturers. The Thermo Fisher Scientific EliA and Inova Diagnostics Quanta Lite (CCP2) tests showed the least between-study variation in sensitivity and specificity suggesting they have the most consistent diagnostic performance overall.
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- Mathsson-Alm, L, et al.
(författare)
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THE NORA PROJECT - PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1090-1090
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Personalized medicine in Rheumatoid arthritis (RA) especially regarding therapy response is still in early stages. The Nordic RA (NORA) project is aiming to improve the prediction of therapy outcome by combining established serologic marker with new markers, genetic information and patient-derived data.Objectives:As an initial step in the project the aim was to select clinically characterized patient cohorts and evaluate if changes or patterns in serological markers could predict therapy response and/or disease progress.Methods:The ARCTIC (Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen) study [1] was designed to compare two tight control treatment strategies for early Rheumatoid arthritis and was used as a first cohort. Plasma samples (n=1622) from 224 RA patients from the ARCTIC study were included and taken at baseline and 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 months from trial start, and analyzed for the presence of EliATM RF (IgM, IgA, IgG), anti-CCP (IgG, IgA) and anti-RA33 (IgM, IgA, IgG) autoantibodies, as well as Calprotectin using the EliA instrument platform (Phadia AB, Uppsala, Sweden). In addition, a custom-made multiplex chip (Thermo Fisher Scientific, Sweden) [2] was used for measurement of anti-IgG antibodies against RA-specific antigens (citrullinated, acetylated and carbamylated), and established CTD-markers (Connective Tissue Disease), e.g. Ro52/60 and dsDNA. The citrullinated peptides on the multiplex chip were both multiple as well as single citrullinated at different positions within the peptide sequence. Additionally, we included an ELISA to measure antibodies against native human collagen II [3].Results:The different single assays in the baseline samples varied between 7 – 80% positive test results, e.g. anti-CCP IgG 80%. For some patients we could see changes in levels for anti-CCP, RF and anti-RA33 in the follow up samples, which varied from negative to more than 3-10xULN (Upper Limit of Normal). For anti-CCP IgG we found 9 patients (4%), who changed from negative to positive (patient 1-5) or from positive to negative (patient 6-8), while patient 9 had a peak at visit 6 (=12 months) and declined afterwards (figure 1). In addition, the above mentioned 9 patients showed clear changes in signal strength for the markers included on the multiplex chip and followed a similar pattern as the anti-CCP IgG signal. Different antibody patterns against single citrullinated peptides were observed and number of ACPA-positive peptides correlated with IgG anti-CCP levels.Figure 1.Anti-CCP IgG value normalised to cutoff (blue line) for patient 1 to 9. The heatmap visualizes the change over time in anti-CCP IgG signal with dark blue showing negative results and orange/red showing results >5xULN.Anti-Collagen II antibodies (anti-CII) were detected in 15% of the baseline samples and in most cases declined over time. Two patients showed low baseline anti-CII levels that increased in the follow up samples. The changes in serological markers and the different reactivity patterns could possibly correlate with clinical outcome and define subgroups of patients with different response to therapy.Results could be repeated in RA patients from the NOR-VEAC [4] cohort. At baseline 73% of the 106 RA patients had a positive anti-CCP IgG result and 11 patients (10%) showed a significant change of anti-CCP IgG level over time.Conclusion:Different response patterns and changes in serological antibody levels over the first 24 months after RA diagnosis could possibly reveal subgroups of patients with different prognosis and response to treatment. Further evaluations in additional treatment cohorts and correlation with clinical data are ongoing.References:[1]Haavardsholm et al., BMJ 2016;354:i4205.[2]Hansson et al. Arthritis Research & Therapy 2012, 14:R201.[3]Manivel et al Ann Rheum Dis. 2017 Sep;76(9):1529-1536.[4]Mjaavatten et al., Arthritis Research & Therapy 2009, 11:R146.Acknowledgements:The NORA project is a NordForsk funded project.Disclosure of Interests:Linda Mathsson-Alm Employee of: Employee of Thermo Fisher Scientific, Isabel Gehring Employee of: Employee of Thermo Fisher Scientific, Maryam Poorafshar Employee of: Employee of Thermo Fisher Scientific, Johan Rönnelid: None declared, Johan Askling Grant/research support from: Research grants from Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, mainly in the context of safety monitoring (ARTIS), Espen Haavardsholm: None declared, Hilde Berner Hammer: None declared
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- Poorafshar, M, et al.
(författare)
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Identification and structural analysis of four serine proteases in a monotreme, the platypus, Ornithorhynchus anatinus
- 2000
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Ingår i: Immunogenetics. - : SPRINGER-VERLAG. - 0093-7711 .- 1432-1211. ; 52:1-2, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- To study the emergence of the major subfamilies of serine proteases during vertebrate evolution, we present here the primary structure of four serine proteases expressed in the spleen of a monotreme, the platypus, Ornithorhynchus anatinus. Partial cDNA clones for four serine proteases were isolated by a PCR-based strategy. This strategy is based on the high level of sequence identity between various members of the large gene family of trypsin-related serine proteases, over two highly conserved regions, those of the histidine and the serine of the catalytic triad. The partial cDNA clones were used to isolate full-length or almost full-length cDNA clones for three of these proteases from a platypus spleen cDNA library. By phylogenetic analysis, these three clones were identified as being the platypus homologues of human coagulation factor X, neutrophil elastase, and a protease distantly related to the T-cell granzymes. The remaining partial clone was found to represent a close homologue of human complement factor D (adipsin). The isolation of these four clones shows that several of the major subfamilies of serine proteases had evolved as separate subfamilies long before the radiation of the major mammalian lineages of today, the monotremes, the marsupials, and the placental mammals. Upon comparison of the corresponding proteases of monotremes and eutherian mammals, the coagulation and complement proteases were shown to display a higher degree of conservation compared to the hematopoietic proteases N-elastase and the T-cell granzymes. This latter finding indicates a higher evolutionary pressure to maintain specific functions in the complement and coagulation enzymes compared to many of the hematopoietic serine proteases.
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