| 1. |
- Berglin, Ewa, MD, PhD, 1955-, et al.
(author)
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Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis : a case-control study
- 2021
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In: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 117
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Journal article (peer-reviewed)abstract
- Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed.Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities.Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively).Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.
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| 2. |
- Bodecker-Zingmark, L., et al.
(author)
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Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease
- 2023
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In: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 68, s. 608-615
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Journal article (peer-reviewed)abstract
- Background: The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.Aims: To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.Methods: Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.Results: The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.Conclusions: We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.
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| 3. |
- Bonroy, Carolien, et al.
(author)
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Detection of antinuclear antibodies : recommendations from EFLM, EASI and ICAP
- 2023
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:7, s. 1167-1198
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Journal article (peer-reviewed)abstract
- Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “Autoimmunity Testing”; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.Conclusions: These recommendations are an important step to achieve high quality ANA testing.
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| 4. |
- Dragon-Durey, Marie-Agnès, et al.
(author)
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Repository of intra-and inter-run variations of quantitative autoantibody assays: A European multicenter study
- 2022
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In: Clinical Chemistry and Laboratory Medicine. - : De Gruyter Open. - 1434-6621 .- 1437-4331. ; 60:9, s. 1373-1383
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Journal article (peer-reviewed)abstract
- No reference data are available on repositories to measure precision of autoantibody assays. The scope of this study was to document inter-and intra-run variations of quantitative autoantibody assays based on a real-world large international data set. Members of the European Autoimmunity Standardisation Initiative (EASI) group collected the data of intra-and inter-run variability obtained with assays quantifying 15 different autoantibodies in voluntary participating laboratories from their country. We analyzed the impact on the assay performances of the type of immunoassay, the number of measurements used to calculate the coefficient of variation (CVs), the nature and the autoantibody level of the internal quality control (IQC). Data were obtained from 64 laboratories from 15 European countries between February and October 2021. We analyzed 686 and 1,331 values of intra-and inter-run CVs, respectively. Both CVs were significantly dependent on: The method of immunoassay, the level of IQC with higher imprecision observed when the antibody levels were lower than 2-fold the threshold for positivity, and the nature of the IQC with commercial IQCs having lower CVs than patients-derived IQCs. Our analyses also show that the type of autoantibody has low impact on the assay' performances and that 15 measurements are sufficient to establish reliable intra-and inter-run variations. This study provides for the first time an international repository yielding values of intra-and inter-run variation for quantitative autoantibody assays. These data could be useful for ISO 15189 accreditation requirements and will allow clinical diagnostic laboratories to assure quality of patient results.
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| 5. |
- Kelderer, Fanny, et al.
(author)
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Associations between pre- and postnatal antibiotic exposures and early allergic outcomes : a population-based birth cohort study
- 2022
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 33:9
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Journal article (peer-reviewed)abstract
- Background: Early life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre- and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.Methods: We included 1387 mother–child dyads from the prospective, population-based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web-based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician-diagnosed asthma; parents (n = 1025) reported physician-diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.Results: Prenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants.Conclusion: Pre- and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.
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| 6. |
- Lundberg, Veronica, 1966-
(author)
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Children with juvenile idiopathic arthritis : health-related quality of life and participation in healthcare encounters
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Background: Growing up with Juvenile Idiopathic Arthritis (JIA) can be associated with functional limitations, feelings of being different, and an impaired health-related quality of life (HRQOL). Children’s and parents’ reports of child HRQOL may differ. Children report difficulties in communicating their problems to healthcare professionals and in participating at healthcare encounters. The overall aim of the thesis was to explore similarities and differences in how girls and boys with JIA and their parents reported child HRQOL, and to explore how children can be enabled to communicate their health concerns and participate at healthcare encounters.Methods: Fifty-three children diagnosed with JIA (38 girls and 15 boys), with a median age of 14 years, and their parents, responded to three HRQOL questionnaires and a screening instrument for mental health. Twenty-three healthcare professionals from different professions in JIA teams participated in focus groups. Four children and two young adults diagnosed with JIA and four parents of children with JIA participated in 10 separate workshops. The focus groups and workshops were analysed using qualitative content analysis.Results: No gender differences were found between girls’ and boys’ self-reported HRQOL and mental health, measured with the questionnaires. Girls reported their HRQOL and mental health better than their parents reported their child’s health in several sub-domains. Boys tended to report their HRQOL worse than their parents reported their child’s health. Children and parents reported the same child HRQOL with the disease specific HRQOL questionnaire.The theme “Creating an enabling arena” illustrates how healthcare professionals face possibilities and challenges when enabling children to communicate and participate in healthcare encounters. Healthcare professionals, parents, and the healthcare system must adjust to the child. Children and their parents cooperated and complemented each other during healthcare encounters. Healthcare professionals addressed the child’s self-identified needs and made the child feel comfortable during encounters. Healthcare professionals’ working methods aided child participation at healthcare encounters, but the healthcare organisation could be a hinder.The theme “Feeling alienated or familiar with healthcare encounters” illustrates how the children needed extra support from healthcare professionals and their parents to be able to participate. Children felt reluctant to engage in healthcare encounters and experienced difficulty expressing how they really felt. Therefore, children must feel safe, understood, and respected by healthcare professionals and receive the help they need. Over time, children felt more comfortable at healthcare encounters once they knew what would happen and once they were assured that healthcare professionals would give them the support they needed to participate.Conclusions: Child and parent differences in the assessment of HRQOL may depend on the questionnaire used. Differences between child and parent reports of child HRQOL must be taken into account at healthcare encounters.Healthcare professionals adjust their interaction and communication with the child depending on the child’s maturity, and talk about the child’s experiences and challenges in everyday life. Collaboration between children and parents before a healthcare encounter and between children, parents, and healthcare professionals during an encounter help children express their wishes and experiences. Healthcare professionals enable child participation by creating a good relationship with the child and their parents, and by strengthening the confidence and autonomy of the child.Children’s active participation in healthcare encounters varies depending on if they feel alienated or familiar with the encounter. Children distance themselves and resist healthcare encounters if they find them emotionally distressing and feel disregarded and labelled. Over time, children can become more familiar and at ease with healthcare situations once they feel safe and experience personal and positive encounters. When children are prepared for the encounter, provided with the space and support they want, and receive tailored help, they are more enabled and empowered to participate.
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| 7. |
- Lundberg, Veronica, et al.
(author)
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How children and adolescents with juvenile idiopathic arthritis participate in their healthcare : health professionals' views
- 2022
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In: Disability and Rehabilitation. - : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 44:10, s. 1908-1915
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Journal article (peer-reviewed)abstract
- Background: The study explores how healthcare professionals view participation of children and adolescents with juvenile idiopathic arthritis, in healthcare encounters.Methods: This qualitative study includes focus groups of HCPs from different professions. The interviews were analysed with qualitative content analysis.Results: The theme “Creating an enabling arena” illuminates how HCPs face possibilities and challenges when enabling children to communicate and participate in clinical encounters. HCPs, parents, and the healthcare system need to adjust to the child. The sub-theme “Bringing different perspectives” describes how children and their parents cooperate and complement each other during healthcare encounters. The sub-theme “Building a safe and comfortable setting” includes how HCPs address the child’s self-identified needs and make the child feel comfortable during encounters. The sub-theme “Facilitating methods in a limiting organisation” includes how HCPs’ working methods and organization may help or hinder child participation during encounters.Conclusions: HCPs encourage children and adolescents to make their views known during healthcare encounters by creating an enabling arena. Collaboration and building good relationships between the child, the parents and the HCPs, before and during the healthcare encounters, can help the child express their wishes and experiences. Clinical examinations and use of technology, such as photos, films and web-bases questionnaires can be a good start for a better child communication in healthcare encounters.
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| 8. |
- Lundberg, Veronica, et al.
(author)
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How children with juvenile idiopathic arthritis view participation and communication in healthcare encounters: a qualitative study
- 2021
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In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Children report that they do not participate in their healthcare as much as they want, despite having the lawful right to form their own views and the right to express those views freely in all matters affecting them. Children and parents appeared to be more satisfied when healthcare professionals (HCP) use a participatory style in healthcare encounters.Aim: To explore how children, adolescents and young adults with Juvenile Idiopathic Arthritis (JIA) and parents of children with JIA view their participation and communication in healthcare encounters with healthcare professionals.Methods: Using a qualitative study design, participatory workshops were held separately for children and young adults with JIA and parents of children with JIA. The workshop data were analysed with Graneheim and Lundman’s Qualitative Content Analysis resulting in one main theme and two subthemes.Results: The theme “Feeling alienated or familiar with healthcare encounters” illuminates how children felt alienated at healthcare encounters if they found the encounters emotionally distressing. Children could withhold information regarding their health and function from both HCPs and their family and friends. The subtheme “Distancing oneself from healthcare” describe why children felt reluctant to engage in the healthcare encounters and experienced difficulty expressing how they really felt. The subtheme “Being a normal event in life” describe how children felt more comfortable over time engaging with HCPs when they knew what would happen, and felt that HCPs gave them the necessary support they needed to participate. Conclusions: Children’s participation in healthcare encounters varied depending if children felt alienated or familiar to the healthcare situations. Children distance themselves and are reluctant to engage in healthcare encounters if they find them emotionally distressing and feel disregarded. Over time, children can become more familiar and at ease with healthcare situations when they feel safe and experience personal and positive encounters. When the children are prepared for the encounter, provided with the space and support they want and receive tailored help they are more enabled to participate.
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| 9. |
- Sack, Ulrich, et al.
(author)
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Quality and best practice in medical laboratories : specific requests for autoimmunity testing
- 2020
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In: Autoimmun Highlights. - : Springer. - 2038-0305 .- 2038-3274. ; 11:1
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Journal article (peer-reviewed)abstract
- Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.
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| 10. |
- Van Hoovels, Lieve, et al.
(author)
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Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns : results of an international survey
- 2020
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In: AUTOIMMUNITY HIGHLIGHTS. - : Springer. - 2038-0305 .- 2038-3274. ; 11:1
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Journal article (peer-reviewed)abstract
- Background The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. Methods Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. Results 438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. Conclusion This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.
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