| 1. |
- Ahmed, Nabeela, et al.
(author)
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Redefining the role of urban studies Early Career Academics in the post-COVID-19 university
- 2022
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In: City. - : Informa UK Limited. - 1360-4813 .- 1470-3629. ; 26:4, s. 562-586
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Journal article (peer-reviewed)abstract
- We are an international collective of Early Career Academics (ECAs) who met throughout 2020 to explore the implications of COVID-19 on precarious academics. With this intervention, our aims are to voice commonly shared experiences and concerns and to reflect on the extent to which the pandemic offers opportunities to redefine Higher Education and research institutions, in a context of ongoing precarity and funding cuts. Specifically, we explore avenues to build solidarity across institutions and geographies, to ensure that the conduct of urban research, and support offered to ECAs, allows for more inclusivity, diversity, security and equitability.
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| 2. |
- Arvidsson, Ida, et al.
(author)
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Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome.
- 2015
-
In: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 194:5, s. 2309-2318
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Journal article (peer-reviewed)abstract
- Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemolytic uremic syndrome (HUS). This study investigated whether Stx2 induces hemolysis and whether complement is involved in the hemolytic process. RBCs and/or RBC-derived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 and C9 by flow cytometry. Patients exhibited increased C3 deposition on RBCs compared with controls (p < 0.001), as well as high levels of C3- and C9-bearing RBC-derived microvesicles during the acute phase, which decreased after recovery. Stx2 bound to P1 (k) and P2 (k) phenotype RBCs, expressing high levels of the P(k) Ag (globotriaosylceramide), the known Stx receptor. Stx2 induced the release of hemoglobin and lactate dehydrogenase in whole blood, indicating hemolysis. Stx2-induced hemolysis was not demonstrated in the absence of plasma and was inhibited by heat inactivation, as well as by the terminal complement pathway Ab eculizumab, the purinergic P2 receptor antagonist suramin, and EDTA. In the presence of whole blood or plasma/serum, Stx2 induced the release of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the absence of factor B, and by purinergic P2 receptor antagonists. Thus, complement-coated RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs with Stx2, which also induced hemolysis. The role of complement in Stx2-mediated hemolysis was demonstrated by its occurrence only in the presence of plasma and its abrogation by heat inactivation, EDTA, and eculizumab. Complement activation on RBCs could play a role in the hemolytic process occurring during STEC-HUS.
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| 3. |
- Canales, Giancarlo De La Torre, et al.
(author)
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The role of tryptophan and its derivatives in musculoskeletal pains : A systematic review and meta-analysis
- 2024
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In: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842.
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Research review (peer-reviewed)abstract
- Background: Studies present ambiguous findings regarding the role of tryptophan and its metabolites, kynurenine and serotonin in chronic musculoskeletal pain. This systematic review aimed to investigate the expression of tryptophan and its metabolites, serotonin and kynurenine in patients with local and generalized chronic musculoskeletal pain in comparison with pain-free controls.Methods: An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to 21 April 2023. Out of 6734 articles, a total of 17 studies were included; 12 studies were used in the meta-analysis of serotonin, 3 regarding tryptophan and 2 studies for a narrative synthesis regarding kynurenine. Risk of bias was assessed using the quality assessment tool for observational cohort and cross-sectional studies of the National Heart, Lung, and Blood Institute, while the certainty of evidence was by GRADE.Results: All included studies showed a low risk of bias. The meta-analysis showed lower blood levels of tryptophan (p < .001; very low quality of evidence) and higher blood levels of serotonin (p < .001; very low-quality evidence) in patients with generalized musculoskeletal pain, when compared to pain-free individuals. In local chronic musculoskeletal pain, there were higher blood levels of serotonin (p=.251; very low quality of evidence) compared to pain-free individuals. Regarding kynurenine, the studies reported both higher and lower blood levels in generalized chronic musculoskeletal pain compared to pain-free individuals.Conclusions: The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.
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| 4. |
- Hellberg, Åsa, et al.
(author)
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An update on the GLOB blood group system and collection.
- 2013
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In: Immunohematology. - 0894-203X. ; 29:1, s. 19-24
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Journal article (peer-reviewed)abstract
- The P blood group antigen of the GLOB system is a glycolipid structure, also known as globoside, on the red blood cells (RBCs) of almost all individuals worldwide. The P antigen is intimately related to the Pk and NOR antigens discussed in the review about the P1PK blood group system. Naturally occurring anti-P is present in the serum of individuals with the rare globoside-deficient phenotypes p, P1k, and P2k and has been implicated in hemolytic transfusion reactions as well as unfavorable outcomes of pregnancy. The molecular genetic basis of globoside deficiency is absence of functional P synthase as a result of mutations at the B3GALNT1 locus. Other related glycolipid structures, the LKE and PX2 antigens, remain in the GLOB blood group collection pending further evidence about the genes and gene products responsible for their synthesis.
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| 5. |
- Hellberg, Åsa, et al.
(author)
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P1PK: the blood group system that changed its name and expanded.
- 2013
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In: Immunohematology. - 0894-203X. ; 29:1, s. 25-33
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Journal article (peer-reviewed)abstract
- The antigens in the P1PK blood group system are carried on glycosphingolipids. The system currently includes three different antigens, P1, Pk, and NOR. The P1 antigen was disovered in 1927 by Landsteiner and Levine, and Pk and NOR were described in 1951 and 1982, respectively. As in the ABO system, naturally occurring antibodies of the immunoglobulin (Ig) M or IgG class, against the missing carbohydrate structures, can be present in the sera of people lacking the corresponding antigen. Anti-P1 is generally a weak and cold-reactive antibody not implicated in hemolytic transfusion reaction (HTR) or hemolytic disease of the fetus and newborn while Pk antibodies can cause HTR, and anti-NOR is regarded as a polyagglutinin. A higher frequency of miscarriage is seen in women with the rare phenotypes p, P1k, and P2k. Furthermore, the Pk and P1 antigens have wide tissue distributions and can act as host receptors for various pathogens and toxins. Why p individuals lack not only Pk and P expression but also P1 has been a longstanding enigma. Recently, it was shown that the same A4GALT-encoded galactosyltransferase synthesizes both the P1 and Pk antigens and that a polymorphism in a new exon in this gene predicts the P1 and P2 phenotypes.
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| 6. |
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| 7. |
- Ricci Hagman, Jennifer, et al.
(author)
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An update on the GLOB blood group system (and former GLOB collection)
- 2018
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In: Immunohematology. - 0894-203X. ; 34:4, s. 161-163
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Journal article (peer-reviewed)abstract
- CONCLUSIONS: The main change that has occurred in the GLOB blood group system since the GLOB review published in this journal in 2013 is the addition of an antigen. The high-prevalence PX2 antigen, originally recognized as the x2 glycosphingolipid, is expressed on red blood cells of most individuals and is elevated in the rare PP1Pk-negative p blood group phenotype. P synthase, encoded by B3GALNT1, was found to elongate paragloboside to PX2 by adding the terminal β3GalNAc moiety. Hence, PX2 was moved from the GLOB collection to the GLOB system. The presence of naturally-occurring anti-PX2 was noted in P1k and P2k individuals exhibiting nonfunctional P synthase. Although the clinical significance of this specificity remains unclear, a recommendation to avoid transfusing Pk patients with p phenotype blood has been made. Currently, 13 mutations at the highly conserved B3GALNT1 locus have been found to abolish P synthase function and are recognized as null alleles by the International Society of Blood Transfusion. A new allele with a missense mutation but resulting in normal expression of P has been assigned GLOB*02. Finally, the GLOB collection was made obsolete after the move of LKE antigen to the 901 series.
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| 8. |
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| 9. |
- Stenfelt, L., et al.
(author)
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The P1 histo-blood group antigen is present on human red blood cell glycoproteins
- 2017
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In: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 112:S1, s. 25-25
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Conference paper (peer-reviewed)abstract
- Background: The P1 antigen was first described in 1927 but not categorized with the Pk antigen in the P1PK histo-blood group system until 2010. Individuals of P1 phenotype have both the Pk and P1 antigens on their red blood cell (RBC) surface, while P2 individuals lack P1 and have lower amounts of Pk. Like in the ABO system, the antigens are carbohydrate epitopes built up stepwise by glycosyltransferases. The antigens of the P1PK system are synthesized by 4-a-galactosyltransferase (a1,4GalT) encoded by A4GALT. Gala4Gal-terminating antigens like Pk and P1 can function as receptors for P-fimbriated Escherichia coli (E. coli). Moreover, the terminal and internal Gala4Galb sequence is a known Shiga toxin receptor. Antibodies against the antigens of the P1PK system are naturally-occurring. Anti-P1 induced hemolytic transfusion reactions are rare but a few cases have been reported. The anti-P1PPk found in plasma from individuals of the p (P1PPk-) phenotype is also associated with recurrent miscarriages. In humans, a1,4GalT has been considered to extend glycans on glycosphingolipids exclusively. However, in certain other species, such as the pigeon, the P1 epitope resides on glycoproteins as well. Interestingly, the majority of the human A, B and H antigens are found on glycoproteins and they share the same precursor as P1, namely paragloboside. Aims: This work is based on a hypothesis stated years ago regarding the P1 glycoepitope. Haselberger et al. [FEBS Lett., 1982] published that P1 is carried on glycoproteins in humans. However, this was later contradicted firmly by Yang et al. [J Biol Chem., 1994]. The aim of this work was to find out if P1 is present on glycoproteins and if so, to characterize carrier candidates on human RBCs. Methods: RBCs from peripheral blood of apparently healthy volunteers were used for the study. P1 phenotyping and SNP genotyping was used to determine P1/P2 status. RBC glycans were digested with a-galactosidase from green coffee bean, a1,3- specific GH110 a-galactosidase of bacterial origin (B-zyme), papain, neuraminidase and/or peptide-N-glycosidase (PNGase) F. RBCs were lysed and the hemoglobin was washed away while the unsealed membranes were collected. Denatured membrane proteins were separated in SDS-PAGE and transferred to a low fluorescence PVDF membrane, immunoblotted with monoclonal anti-P1 and staining quantified in relation to total protein loaded. Results: We show clearly that P1 occurs on various glycoproteins, seen as a smearlike pattern in Western blots with cell membranes from P1 but not P2 or p RBCs. Furthermore, there was a significant difference between the staining of RBCs from P1-homozygous (stronger) and P1-heterozygous (weaker) individuals. The amount detected varied between samples of the same genotype, which is consistent with earlier studies of P1 expression on RBCs. A tendency toward a banding pattern suggested possible carriers at ∼50 and ∼100 kDa. P1 staining was lost after treatment of the RBCs with coffee bean a-galactosidase as the enzyme destroys the P1 epitope. PNGase F treatment reduced the P1 signal whilst B-zyme did not. Summary/Conclusions: This study provides data showing that P1 does indeed reside on human RBC glycoproteins and not only on glycosphingolipids. The epitope was detected in a gene-dose dependent manner on glycoproteins of P1-positive RBC membranes. The signal was reduced when using N-glycan-specific PNGase F, indicating that at least some of the epitopes are carried on N-glycans, which mimics the ABH antigens. Attempts to identify specific carrier proteins are in progress.
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| 10. |
- Stenfelt, Linn, et al.
(author)
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The P1 histo-blood group antigen is present on human red blood cell glycoproteins
- 2019
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In: Transfusion. - : Wiley. - 0041-1132. ; 59:3, s. 1108-1117
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Journal article (peer-reviewed)abstract
- BACKGROUND: The P1 antigen was first described in 1927 and belongs to the P1PK histo-blood group system, together with Pk and NOR. The A4GALT-encoded 4-α-galactosyltransferase synthesizes these antigens and has been considered to extend glycolipids exclusively. However, contradicting studies have been published regarding the presence of P1 on human glycoproteins. In other species, P1 occurs on glycoproteins. Furthermore, human ABH antigens occur on both glycolipids and glycoproteins and are biochemically related to P1. Thus, we hypothesized that P1 is present on RBC glycoproteins in humans. STUDY DESIGN AND METHODS: RBCs of known P1/P2 status (phenotype and rs8138197 genotype) were used. The RBC surface glycans were modified with α-galactosidases, papain, and/or peptide-N-glycosidase F. RBC membrane proteins were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis/immunoblot. A new P1/P2-allelic discrimination assay based on rs5751348 was validated. RESULTS: P1 occurs on various glycoproteins, seen as smearlike patterns in anti-P1-stained immunoblots with RBC membranes of P1 but not P2 or p phenotype. There was a significant difference between the staining of P1-homozygous and P1-heterozygous RBCs (P1P1 > P1P2), as well as intragenotypic variation. Immunoblotting banding patterns show major carriers at approximately 50 and 100 kDa. P1 staining was lost after treatment of RBCs with α-galactosidase of broad Galα-1,3/4/6-specificity. Peptide-N-glycosidase F treatment reduced the P1 signal, while papain or α-1,3-specific galactosidase did not. P1/P2 status was confirmed by a new rs5751348 assay. CONCLUSION: Our data indicate that the P1 antigen can reside on human RBC glycoproteins. Glycosidase studies suggest that at least part of the epitopes occur on N-glycans.
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| 11. |
- Stenfelt, Linn, et al.
(author)
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The P1PK blood group system : revisited and resolved
- 2020
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In: Immunohematology. - 0894-203X. ; 36:3, s. 99-103
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Journal article (peer-reviewed)abstract
- CONCLUSIONS: This update on the P1PK blood group system (Hellberg Å, Westman JS, Thuresson B, Olsson ML. P1PK: the blood group system that changed its name and expanded. Immunohematology 2013;29:25-33) provides recent findings concerning the P1PK blood group system that have both challenged and confirmed old theories. The glycosphingolipids can no longer be considered the sole carriers of the antigens in this system because the P1 antigen has been detected on human red blood cell glycoproteins. New indications suggest that P1Pk synthase activity truly depends on the DXD motif, and the genetic background and molecular mechanism behind the common P1 and P2 phenotypes were found to depend on transcriptional regulation. Transcription factors bind the P1 allele selectively to a motif around rs5751348 in a regulatory region of A4GALT, which enhances transcription of the gene. Nonetheless, unexplained differences in antigen expression between individuals remain.
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| 12. |
- Suppiah, Ravi, et al.
(author)
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A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis.
- 2011
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 899-905
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Journal article (peer-reviewed)abstract
- Objective. Assessment of disease activity in vasculitis can be achieved using the BVAS, a clinical checklist of relevant symptoms, signs and features of active disease. The aim of this study was to revalidate the BVAS version 3 (BVAS v. 3) in a cohort of patients with systemic vasculitis. Methods. A total of 238 patients with vasculitis from seven countries in Europe were evaluated at a single time point. Spearman's correlation coefficients were calculated between BVAS v. 3 scores, vasculitis activity index (VAI), physician's global assessment (PGA), the physician's treatment decision, CRP and the vasculitis damage index (VDI) to demonstrate that the BVAS v. 3 measures disease activity. Results. WG (63%), Churg-Strauss syndrome (9%) and microscopic polyangiitis (9%) were the most common diagnoses. The BVAS v. 3 showed convergent validity with the VAI [ρ = 0.82 (95% CI 0.77, 0.85)], PGA [ρ = 0.85 (95% CI 0.81, 0.88)] and the physician's treatment decision [ρ = 0.54 (95% CI 0.44, 0.62)]. There was little or no correlation between BVAS v. 3 and the CRP level [ρ = 0.18 (95% CI 0.05, 0.30)] or with the VDI [ρ = -0.10 (95% CI 0.22, 0.03)]. The inter-observer reliability was very high with an intra-class correlation coefficient (ICC) of 0.996 (95% CI 0.990, 0.998) for the total BVAS v. 3 score. Conclusion. The BVAS v. 3 has been evaluated in a large cohort of patients with vasculitis and the important properties of the tool revalidated. This study increases the utility of the BVAS v. 3 in different populations of patients with systemic vasculitis.
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| 13. |
- Suppiah, Ravi, et al.
(author)
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Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index
- 2011
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:1, s. 80-85
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Journal article (peer-reviewed)abstract
- Objectives To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis. Methods A total of 283 patients with vasculitis from 11 European centres were evaluated in a cross-sectional study using the VDI and CDA. Results Wegener's granulomatosis (58.4%) and microscopic polyangiitis (11.0%) were the most common diagnoses. Agreement between VDI and CDA scores (Spearman's correlation) was 0.90 (95% CI 0.87 to 0.92). There was good correlation between individual comparably evaluated organ systems (Spearman's correlation 0.70-0.94). Interobserver reliability (assessed by intraclass correlation coefficient (ICC)) was 0.94 (95% CI 0.89 to 0.98) for VDI and 0.78 (95% CI 0.63 to 0.93) for CDA. Intraobserver reliability was 0.92 (95% CI 0.83 to 1.00) for VDI and 0.87 (95% CI 0.75 to 1.00) for CDA. A total of 13 items were not used in the VDI compared to 23 in the CDA. Observers agreed that the CDA covered the full spectrum of damage attributable to vasculitis but was more time consuming and thus possibly less feasible for clinical and research purposes. Conclusions The VDI and CDA capture reliable data on damage among patients with vasculitis. The CDA captures more detail but is more complex and less practical than the VDI. Further evolution of damage assessment in vasculitis is likely to include key elements from both instruments.
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| 14. |
- Thuresson, Britt, et al.
(author)
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Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups.
- 2011
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:2, s. 678-687
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Journal article (peer-reviewed)abstract
- The A4GALT locus encodes a glycosyltransferase that synthesizes the terminal Galα1-4Gal of the P(k)(Gb3/CD77) glycosphingolipid, important in transfusion medicine, obstetrics and pathogen susceptibility. Critical nucleotide changes in A4GALT not only abolish P(k) formation but also another Galα1-4Gal-defined antigen, P1, which belongs to the only blood group system for which the responsible locus remains undefined. Since known A4GALT polymorphisms do not explain the P1-P(k)+ phenotype, P(2), we set out to elucidate the genetic basis of P(1)/P(2). Despite marked differences (P(1)>P(2)) in A4GALT transcript levels in blood, luciferase experiments showed no difference between P(1)/P(2)-related promoter sequences. Investigation of A4GALT-mRNA in cultured human bone marrow cells revealed novel transcripts containing only the non-coding exon 1 and a sequence (here termed exon 2a) from intron 1. These 5'-capped transcripts include poly-A tails and 3 polymorphic sites, one of which was P(1)/P(2)-specific among >200 donors and opens a short reading frame in P(2) alleles. We exploited these data to devise the first genotyping assays to predict P1 status. P(1)/P(2) genotypes correlated with both transcript levels and P1/P(k) expression on red cells. Thus, P(1) zygosity partially explains the well-known interindividual variation in P1 strength. Future investigations need to focus on regulatory mechanisms underlying P1 synthesis.
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| 15. |
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| 16. |
- Westman, Julia
(author)
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Genetics and Expression of Glycosphingolipids in the P1PK and GLOB Histo-Blood Group Systems
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- The glycosphingolipid (GSL) antigens in the clinically important P1PK and GLOB blood group systems are present on erythrocytes as well as other tissues and are so-called histo-blood group antigens. Blood group antigens of carbohydrate nature are products of enzymes, so-called glycosyltransferases, adding sugars in a step-wise manner to an acceptor substrate. Presence or absence of the P1PK and GLOB antigens gives rise to the common P1 and P2 (P1−) phenotypes as well as the rare but clinically important p, P1k and P2k phenotypes. The aim of this thesis was to explore the molecular genetics underlying the expression of the antigens in the P1PK and GLOB histo-blood group systems by analyzing the genes responsible for their expression, A4GALT and B3GALNT1, respectively. Investigation of potential regulatory regions of the A4GALT identified a SNP in a novel exon, denoted exon 2a, which correlates with the P1/P2 phenotypes. A P1/P2-discriminating SNP enabled genotypic prediction of P1 status in >200 samples. Presence of one or two P1 allele(s) resulted in increased A4GALT transcript levels and more Pk and P1 antigens on erythrocytes, compared to homozygosity for a P2 allele. The A4GALT-encoded enzyme α1,4Gal-T was thereby linked to synthesis of the two α1,4Gal-terminating antigens, Pk and P1, and consequently the former P blood group system was renamed to P1PK based on these findings. Critical mutations in the A4GALT open reading frame (ORF), give rise to the PP1Pk-negative p phenotype, whilst B3GALNT1-null alleles result in the P-deficient P1k/P2k phenotypes. P1/P2 genotyping revealed that the p phenotype can arise on both P1 and P2 alleles, whilst the presence or absence of P1 antigen was predicted in 92% of the P1k/P2k samples. In addition, a novel genetic explanation underlying the p phenotype was identified, where three different alleles were shown to have an intact A4GALT ORF but instead had large deletions comprising the promoter and non-coding exons 1 and 2a. The number of p- and P1k/P2k-inducing mutations was increased by these studies as new alterations were identified in A4GALT and B3GALNT1, respectively. Interestingly, p phenotype cells express a GSL named x2 that was shown here to be absent on erythrocytes of the P1k/P2k phenotypes. This structure was recently acknowledged as a blood group antigen under the name PX2, since anti-PX2 is present in P1k/P2k plasma. PX2 is a β1,3GalNAc-elongation of paragloboside, a neolacto series GSL. Overexpression and knock-down of B3GALNT1 in a cellular system revealed that β1,3GalNAc-T1 encoded by this gene is responsible for both P and PX2 antigen expression. As a consequence of these findings, PX2 was removed from the GLOB blood group collection to join P as the second antigen in the GLOB blood group system. This thesis work further emphasizes the molecular and genetic diversity of the P1PK and GLOB histo-blood group systems. It also highlights the fact that these glycosyltransferases are more versatile than previously thought. For instance, both α1,4Gal-T (Pk and P1) and β1,3GalNAc-T1 (P and PX2) are able to synthesize more than one GSL antigen by utilizing more than one acceptor. Future work will hopefully gain further knowledge of these GSL antigens and their extensions, as well as their function in health and disease.
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| 17. |
- Westman, Julia, et al.
(author)
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Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes
- 2015
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:30, s. 18505-18518
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Journal article (peer-reviewed)abstract
- The x(2) glycosphingolipid is expressed on erythrocytes from individuals of all common blood group phenotypes and elevated on cells of the rare P/P1/P-k-negative p blood group phenotype. Globoside or P antigen is synthesized by UDP-N-acetylgalactosamine: globotriaosyl-ceramide 3-beta-N-acetylgalactosaminyl-transferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAc beta 3Gal, as x(2). We encountered a patient with mutations in B3GALNT1 causing the rare P-deficient P-1(k) phenotype and whose pretransfusion plasma was unexpectedly incompatible with p erythrocytes. The same phenomenon was also noted in seven other unrelated P-deficient individuals. Thin-layer chromatography, mass spectrometry, and flow cytometry were used to show that the naturally occurring antibodies made by p individuals recognize x(2) and sialylated forms of x(2), whereas x(2) is lacking on P-deficient erythrocytes. Overexpression of B3GALNT1 resulted in synthesis of both P and x(2). Knockdown experiments with siRNA against B3GALNT1 diminished x(2) levels. We conclude that x(2) fulfills blood group criteria and is synthesized by UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase. Based on this linkage, we proposed that x(2) joins P in the GLOB blood group system (ISBT 028) and is renamed PX2 (GLOB2). Thus, in the absence of a functional P synthase, neither P nor PX2 are formed. As a consequence, naturally occurring anti-P and anti-PX2 can be made. Until the clinical significance of anti-PX2 is known, we also recommend that rare P-1(k) or P-2(k) erythrocyte units are preferentially selected for transfusion to P-k patients because p erythrocytes may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels.
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| 18. |
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| 19. |
- Westman, Julia, et al.
(author)
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P1/P2 genotyping of known and novel null alleles in the P1PK and GLOB histo-blood group systems.
- 2013
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In: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 53:11, s. 2928-2939
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Journal article (peer-reviewed)abstract
- The rare but clinically important null phenotypes of the P1PK and GLOB blood group systems are due to alterations in A4GALT and B3GALNT1, respectively. A recently identified single-nucleotide polymorphism in Exon 2a of A4GALT predicts the common P1 and P2 phenotypes but rare variants have not been tested.
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| 20. |
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| 21. |
- Westman, Julia S., et al.
(author)
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Allele-selective RUNX1 binding regulates P1 blood group status by transcriptional control of A4GALT
- 2018
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 131:14, s. 1611-1616
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Journal article (peer-reviewed)abstract
- P1 and Pk are glycosphingolipid antigens synthesized by the A4GALT-encoded α1,4-galactosyltransferase, using paragloboside and lactosylceramide as acceptor substrates, respectively. In addition to the compatibility aspects of these histo-blood group molecules, both constitute receptors for multiple microbes and toxins. Presence or absence of P1 antigen on erythrocytes determines the common P1 (P1+Pk+) and P2 (P1-Pk+weak) phenotypes. A4GALT transcript levels are higher in P1 individuals and SNPs in non-coding regions of A4GALT, particularly rs5751348, correlate with P1/P2 status. Despite these recent findings, the molecular mechanism underlying these phenotypes remains elusive. The In(Lu) phenotype is caused by KLF1 haploinsufficiency and shows decreased P1 levels on erythrocytes. We therefore hypothesized KLF1 to regulate A4GALT expression. Intriguingly, P1 -specific sequences including rs5751348 revealed potential binding sites for several hematopoietic transcription factors, including KLF1. However, KLF1 binding did not explain P1-specific EMSA shifts and siRNA silencing of KLF1 did not affect A4GALT transcript levels. Instead, protein pull-down experiments using P1 but not P2 oligonucleotide probes identified RUNX1 by mass spectrometry. Furthermore, RUNX1 binds P1 alleles selectively and knockdown of RUNX1 significantly decreased A4GALT transcription. These data indicate that RUNX1 regulates A4GALT and thereby the expression of clinically important glycosphingolipids implicated in blood-group incompatibility and host-pathogen interactions.
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| 22. |
- Yates, Max, et al.
(author)
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Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts
- 2017
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In: RMD Open. - : BMJ. - 2056-5933. ; 3:1
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Journal article (peer-reviewed)abstract
- The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society - EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases.
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