| 1. |
- Aurelius, Johan, 1980, et al.
(author)
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Anthracycline-based consolidation may determine outcome of post-consolidation immunotherapy in AML
- 2019
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In: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:11, s. 2771-2778
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Journal article (peer-reviewed)abstract
- Consolidation chemotherapy in acute myeloid leukemia (AML) aims at eradicating residual leukemic cells and mostly comprises high-dose cytarabine with or without the addition of anthracyclines, including daunorubicin. Immunogenic cell death (ICD) may contribute to the efficacy of anthracyclines in solid cancer, but the impact of ICD in AML is only partly explored. We assessed aspects of ICD, as reflected by calreticulin expression, in primary human AML blasts and observed induction of surface calreticulin upon exposure to daunorubicin but not to cytarabine. We next assessed immune phenotypes in AML patients in complete remission (CR), following consolidation chemotherapy with or without anthracyclines. These patients subsequently received immunotherapy with histamine dihydrochloride (HDC) and IL-2. Patients who had received anthracyclines for consolidation showed enhanced frequencies of CD8(+) T-EM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.
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| 2. |
- Einarsdottir, Sigrun, et al.
(author)
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Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
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In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
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Journal article (peer-reviewed)abstract
- Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
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| 3. |
- Lagging, Martin, 1965, et al.
(author)
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Reply.
- 2014
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In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 60:6, s. 2130-1
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Journal article (other academic/artistic)
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| 4. |
- Lindh, Magnus, 1960, et al.
(author)
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Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
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In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4, s. e82-e89
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Journal article (peer-reviewed)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 5. |
- Lindh, Magnus, 1960, et al.
(author)
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Hepatitis C treatment response kinetics and impact of baseline predictors.
- 2011
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In: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
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Journal article (peer-reviewed)abstract
- Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
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| 6. |
- Lindh, Magnus, 1960, et al.
(author)
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IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
- 2011
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In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7, s. e325-e331
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Journal article (peer-reviewed)abstract
- Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7 days of therapy was more pronounced (P < 0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' = 1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P = 0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
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| 7. |
- Lindh, Magnus, 1960, et al.
(author)
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Interleukin 28B Gene Variation at rs12979860 Determines Early Viral Kinetics During Treatment in Patients Carrying Genotypes 2 or 3 of Hepatitis C Virus
- 2011
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:12, s. 1748-1752
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Journal article (peer-reviewed)abstract
- Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon lambda 3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CCrs12979860 had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CTrs1297986 or TTrs1297986. The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.
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| 8. |
- Martner, Anna, 1979, et al.
(author)
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Transient and durable T cell reactivity after COVID-19
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 119:30
-
Journal article (peer-reviewed)abstract
- This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until similar to 70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-gamma remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T-H) cells followed by an equally synchronous and durable T(H)1-like reactivity reflecting long-lasting T cell memory.
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| 9. |
- Mossberg, Natalia, et al.
(author)
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Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré
- 2010
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In: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 7
-
Journal article (peer-reviewed)abstract
- Background: The recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst”) in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS. Methods: Oxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val- Met-NH2 (WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase. Results: Disease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003). Conclusion: We conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS
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| 10. |
- Mossberg, Natalia, et al.
(author)
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Oxygen radical production and severity of the Guillain--Barré syndrome.
- 2007
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In: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 192:1-2, s. 186-91
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Journal article (peer-reviewed)abstract
- The NADPH oxidase-dependent formation of reactive oxygen species ("oxygen radicals") by phagocytic cells constitutes an important part of the innate immune defence against microorganisms. Recent studies in animal models imply that a deficient function of the NADPH oxidase may be linked to the development of autoimmunity, but a link between oxygen radical production and severity of autoimmune disease in humans has not been established. We have examined the oxygen radical production in peripheral blood leukocytes from patients with the Guillain-Barré syndrome (GBS). Leukocytes from GBS patients in a stationary phase 1-5 years after their acute episode were activated by the formyl peptide receptor (FPR) ligand formyl-Met-Leu-Phe (fMLF) or the closely related formyl peptide like receptor 1 (FPRL1) ligand Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM). The patients were dichotomized according to severity by 1) the requirement of intensive care unit treatment and 2) the ability to walk independently after 3 months. Our data show that the amount of superoxide release following challenge with either of the two agonists fMLF and WKYMVM was significantly lower in patients requiring intensive care unit treatment or unable to walk after 3 months. Results obtained with the global activator phorbol myristate acetate, as well as with fMLF in TNF alpha-primed leukocytes, suggested that the deficiency of oxygen radical production in patients with severe GBS was the result of a specific deficiency of radical production in response to FPR/FPRL1 ligands rather than an inherent deficiency of NADPH oxidase function.
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