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- Heyder, T, et al.
(författare)
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Altered Fc galactosylation in IgG4 is a potential serum marker for chronic lung disease
- 2018
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Characterising chronic lung diseases is challenging. New, less invasive diagnostics are needed to decipher disease pathologies and subphenotypes. Fc galactosylation is known to affect IgG function, and is altered in autoimmune disorders and under other pathological conditions. We tested how well Fc glycans in IgG from bronchoalveolar lavage fluid (BALF) and serum correlated, and if the Fc glycan profile could reveal pulmonary inflammation.A shotgun proteomics approach was used to profile Fc glycans in serum and BALF of controls (n=12) and sarcoidosis phenotypes (Löfgren's syndrome (LS), n=11; and non-LS, n=12). Results were further validated in severe asthma (SA) (n=20) and published rheumatoid arthritis (RA) patient data (n=13) including clinical information.Intra-individually, Fc-galactosylation status of IgG1 (R2=0.87) and IgG4 (R2=0.95) correlated well between matrixes. Following GlycoAge-index correction, the ratio between agalactosylated and digalactosylated Fc glycans of IgG4 could distinguish sarcoidosis and SA from healthy and RA subjects with a mean±se area under the curve (AUC) of 78±6%. The AUC increased to 83±6% using the more chronic lung disease types (non-LS and SA) and most strikingly, to 87±6% for the SA subgroup.The results indicate that the Fc galactosylation status of IgG4 is a potential blood test marker for chronic lung inflammation.
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- Häggmark, Anna, et al.
(författare)
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Proteomic Profiling Reveals Autoimmune Targets in Sarcoidosis
- 2015
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 191:5, s. 574-583
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related autoantigens. Objectives: We investigated bronchoalveolar lavage (BAL) and serum samples from patients with sarcoidosis and healthy and diseased control subjects to discover sarcoidosis-associated autoantigens. Methods: Antigen microarrays built on 3,072 protein fragments were used to screen for IgG reactivity in 73 BAL samples from subjects with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples and 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis and 269 plasma samples from patients diagnosed with myositis. Measurements and Main Results: Reactivity toward zinc finger protein 688 and mitochondrial ribosomal protein L43 were discovered with higher frequencies in patients with sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with non-Lofgren syndrome. Increased reactivity toward nuclear receptor coactivator 2 was also observed in patients with non-Lofgren syndrome as compared with patients with Lofgren syndrome. The antigen representing adenosine diphosphate-ribosylation factor GTPase activating protein 1 revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in patients with sarcoidosis. Conclusions: Autoantigen reactivity was present in most BAL and serum samples analyzed, and the results revealed high interindividual heterogeneity, with most of the reactivities observed in single individuals only. Four proteins are here proposed as sarcoidosis-associated autoimmune targets and of interest for further validation in independent cohorts.
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- Lundstrom, SL, et al.
(författare)
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SpotLight Proteomics-A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications
- 2019
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:9
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Tidskriftsartikel (refereegranskat)abstract
- Sarcoidosis is a systemic interstitial lung disease of unknown aetiology. Less invasive diagnostics are needed to decipher disease pathology and to distinguish sub-phenotypes. Here we test if SpotLight proteomics, which combines de novo MS/MS sequencing of enriched IgG and co-extracted proteins with subsequent label-free quantification of new and known peptides, can differentiate controls and sarcoidosis phenotypes (Löfgrens and non-Löfgrens syndrome, LS and nonLS). Intra-individually matched IgG enriched from serum and bronchial lavage fluid (BALF) from controls (n = 12), LS (n = 11) and nonLS (n = 12) were investigated. High-resolution mass-spectrometry SpotLight proteomics and uni- and multivariate-statistical analyses were used for data processing. Major differences were particularly observed in control-BALF versus sarcoidosis-BALF. However, interestingly, information obtained from BALF profiles was still present (but less prominent) in matched serum profiles. By using information from orthogonal partial least squares discriminant analysis (OPLS-DA) differentiating 1) sarcoidosis-BALF and control-BALF and 2) LS-BALF vs. nonLS-BALF, control-serum and sarcoidosis-serum (p = 0.0007) as well as LS-serum and nonLS-serum (p = 0.006) could be distinguished. Noteworthy, many factors prominent in identifying controls and patients were those associated with Fc-regulation, but also features from the IgG-Fab region and novel peptide variants. Differences between phenotypes were mostly IgG-specificity related. The results support the analytical utility of SpotLight proteomics which prospectively have potential to differentiate closely related phenotypes from a simple blood test.
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