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Sökning: WFRF:(Asplund Högelin K.)

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1.
  • Longinetti, E., et al. (författare)
  • SARS-COV2 exposure rates and serological response of people living with MS
  • 2022
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 515-516
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Some multiple sclerosis (MS) disease-modifying therapies (DMTs) are  associated with blunted humoral vaccination responses, but relevance for SARS-CoV-2 infection is unclear.Objectives: To determine  SARS-CoV-2  exposure  rates  and  formation of antibody memory among participants of the COMparison Between   All   immunoTherapies   for   MS   (COMBAT-MS;   NCT03193866) and the Immunomodulation and MS Epidemiology (IMSE) studies.Aim: To determine SARS-CoV2 serological response of people living with MS (pwMS).Methods: Using  a  multiplex  bead-based  assay  we  determined  SARS-CoV-2  spike  and  nucleocapsid  antibody  levels  in  3,723  pwMS   in   paired   serum   samples   (n=7,157)   donated   prior   (Results: Specificity and sensitivity of the assay for SARS-CoV-2 was  100%  and  99.7%,  respectively.  The  proportion  of  positive  samples for SARS-CoV-2 differed moderately across DMTs with the highest values among cladribine-treated (7.4%) and the lowest number  among  rituximab-treated  pwMS  (3.9%). Similarly,  the  proportion of positive cases not reported in the Swedish MS registry varied from 100% for cladribine to 33.3% among untreated pwMS.  Comparing levels  of  antibodies  titers  showed  that  levels  were lower among those treated with rituximab or fingolimod vs interferon treated pwMS. Point estimates indicated a similar trend comparing rituximab or fingolimod vs untreated pwMS.Conclusions: Overall  rates  of  SARS-CoV-2  antibody  positivity  after  the  first COVID-19  wave  differed  only  moderately  across  DMTs,  while  antibody  levels were  lower  with  rituximab  or  fingolimod  compared  to  interferon-treated pwMS.  This  indicates  quantitative  rather  than  qualitative  differences  in  the humoral  response to infection.
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2.
  • Asplund Högelin, K., et al. (författare)
  • B-cell repopulation dynamics and drug pharmacokinetics impact SARS-CoV-2 vaccine efficacy in anti-CD20-treated multiple sclerosis patients
  • 2022
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:11, s. 3317-3328
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Recent findings document a blunted humoral response to SARS-CoV-2 vaccination in patients on anti-CD20 treatment. Although most patients develop a cellular response, it is still important to identify predictors of seroconversion to optimize vaccine responses. Methods: We determined antibody responses after SARS-CoV-2 vaccination in a real-world cohort of multiple sclerosis patients (n = 94) treated with anti-CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4–9.6 years) and time from last anti-CD20 infusion to vaccination (median = 190, range = 60–1032 days). Results: We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of >0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval [CI] = 1.0–28.1, p = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20–10.15, p = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002–0.392, p = 0.012). Furthermore, naïve and memory IgG+ B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike-specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon-γ and/or interleukin-13 T-cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels. Conclusions: These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit–risk with anti-CD20. 
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