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  • Moberg, Christina, et al. (författare)
  • De unga gör helt rätt när de stämmer staten
  • 2022
  • Ingår i: Aftonbladet. - : Aftonbladet Hierta AB. - 1103-9000.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
  • Bahnan, Wael, et al. (författare)
  • A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function
  • 2023
  • Ingår i: EMBO Molecular Medicine. - : Wiley-Blackwell. - 1757-4684 .- 1757-4676.
  • Tidskriftsartikel (refereegranskat)abstract
    • Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface-bound M protein. Such antibodies are typically non-opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual-Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual-Fab cis-binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single-Fab mode to the same region cannot bypass the M protein's virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti-streptococcal therapy. Our findings highlight the concept of dual-Fab cis binding as a means to access conserved, and normally non-opsonic regions, regions for protective antibody targeting.
  • Bergqvist, David, et al. (författare)
  • Inga dödsfall/slaganfall efter kirurgi vid asymtomatisk karotisstenos : femårsresultat redovisat i riksstäckande register
  • 2006
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:5, s. 301-302
  • Tidskriftsartikel (refereegranskat)abstract
    • In the Swedish vascular registry 7473 carotid endarterectomies are registered, in 10% the indication being a symptomatic stenosis. There are great variations in indication for carotid endarterectomy within Sweden. During the last five years the combined postoperative mortality and/or postoperative permanent stroke has varied between 3% in 1999 and 1.5% in 2003. During the same period not a single patient operated on for a symptomatic carotid stenosis experienced these complications.
  • Björck, Lars, et al. (författare)
  • Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus
  • 1990
  • Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X. ; 64:2, s. 941-943
  • Tidskriftsartikel (refereegranskat)abstract
    • Cystatin C is a human cysteine proteinase inhibitor present in extracellular fluids. Cystatin C and a tripeptide derivative (Z-LVG-CHN2) that mimics its proteinase-binding center, were tested for possible antiviral activity against herpes simplex virus type 1 (HSV) and poliovirus type 1. Both recombinant cystatin C and Z-LVG-CHN2 displayed strong inhibitory effects on HSV replication, whereas no significant effect on poliovirus replication was seen. The molar concentration of cystatin C that gave total inhibition of HSV replication was lower than that of either Z-LVG-CHN2 or of acyclovir, the drug currently most used against HSV infections. These results suggest that cysteine proteinase inhibitors might play a physiological role as inhibitors of viral replication and that such proteinase inhibitors, or peptide derivatives that mimic their proteinase-binding centers, might be used as antiviral agents.
  • Björck, M, et al. (författare)
  • Twenty years with the Swedvasc Registry.
  • 2008
  • Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 35:2, s. 129-30
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Forsberg, Anna, et al. (författare)
  • Colonoscopy findings in high-risk individuals compared to an average-risk control population
  • 2015
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:7, s. 866-874
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.
  • Forsberg, Anna M., et al. (författare)
  • Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study
  • 2012
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:2, s. 184-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.
  • Happonen, Lotta, et al. (författare)
  • A quantitative Streptococcus pyogenes-human protein-protein interaction map reveals localization of opsonizing antibodies
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10:1, s. 2727-2727
  • Tidskriftsartikel (refereegranskat)abstract
    • A fundamental challenge in medical microbiology is to characterize the dynamic protein-protein interaction networks formed at the host-pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes, and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and different S. pyogenes serotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis of S. pyogenes cells are localized. The interaction map confirms several previously described protein-protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host-pathogen interactions involving other bacterial species.
  • Lorant, Tomas, 1975-, et al. (författare)
  • Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients
  • 2018
  • Ingår i: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 18:11, s. 2752-2762
  • Tidskriftsartikel (refereegranskat)abstract
    • Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19+ memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA-incompatible donor (HLA-B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.
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