| 1. |
- Ahlgren, Kerstin M., et al.
(författare)
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Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model
- 2011
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 41:1, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
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| 2. |
- Ahrén-Moonga, Jennie, et al.
(författare)
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Levels of tumour necrosis factor-alpha and interleukin-6 in severely ill patients with eating disorders
- 2011
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 63:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits. Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality. Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman's rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression. Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits.
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| 3. |
- Baecklund, Eva, 1956-, et al.
(författare)
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Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis
- 2018
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 270-275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.METHOD: subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.CONCLUSION: In this study, neither anti-CCP antibodies (IgG, IgG1–4, IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA
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| 4. |
- Boman, Antonia, et al.
(författare)
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Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis : a prospective longitudinal inception cohort study
- 2019
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Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.Methods: The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.Results: Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.Conclusions: Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.
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| 5. |
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| 6. |
- Brink, Mikael, et al.
(författare)
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Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage
- 2015
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P < 0.001) and also increased significantly after disease onset (P < 0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P < 0.05, all). Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.
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| 7. |
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| 8. |
- Brink, Mikael, et al.
(författare)
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Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis
- 2022
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4985-4990
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. Results In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60-75, fibrinogen (Fib)beta 62-78 (72), Fib alpha 621-635, Bla26, collagen (C)II359-369 and F4-CIT-R (P < 0.01 to P < 0.05). The number of ACPA specificities was also related to PF development (P < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P < 0.05 in all models), anti-Vim60-75 (P < 0.05, in all models), anti-Fib beta 62-78 (72) (P < 0.001 to P < 0.05), anti-CII359-369 (P < 0.05 in all models) and anti-F4-CIT-R AQ4 (P < 0.01 to P < 0.05), anti-Fib alpha 621-635 (P < 0.05 in one) and anti-Bla26 (P < 0.05 in two) were significantly associated with PF development. Conclusion The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes.
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| 9. |
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| 10. |
- Brink, Mikael, et al.
(författare)
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Multiplex Analyses of Antibodies Against Citrullinated Peptides in Individuals Prior to Development of Rheumatoid Arthritis
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:4, s. 899-910
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Tidskriftsartikel (refereegranskat)abstract
- Objective The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. Methods A casecontrol study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen 573 (Fib573), Fib591, Fib3652, Fib72, Fib74, -enolase (citrullinated -enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 217 (Vim217), and Vim6075, were analyzed using a microarray system. Results The fluorescence intensity of antibodies against Fib3652, Fib74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (P < 0.001). The levels of the earliest-detectable antibodies (Fib591 and Vim6075) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fib3652, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fib573, and Fib74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fib3652 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.882.3) compared with having either antibody alone. Conclusion Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fib3652, and filaggrin, increasing during the predating time period closer to the onset of symptoms.
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