Secondary immunodeficiency associated with the use of antilymphocytic serum

1980 ◽  
Vol 89 (1) ◽  
pp. 39-41
Author(s):  
V. T. Antonenko ◽  
N. I. Lisyanyi
Keyword(s):  
Antilymphocytic Serum ◽  
Secondary Immunodeficiency

scholarly journals A Review of Vaccinations in Adult Patients with Secondary Immunodeficiency

2021 ◽  
Author(s):  
Elda Righi ◽  
Tolinda Gallo ◽  
Anna Maria Azzini ◽  
Fulvia Mazzaferri ◽  
Maddalena Cordioli ◽  
...  
Keyword(s):  
Adult Patients ◽  
Secondary Immunodeficiency

scholarly journals Antilymphocytic Serum

1970 ◽  
Vol 63 (9) ◽  
pp. 949-950
Author(s):  
A J Woiwod
Keyword(s):  
Antilymphocytic Serum

scholarly journals Heme-stress activated NRF2 skews fate trajectories of bone marrow cells from dendritic cells towards red pulp-like macrophages in hemolytic anemia

2022 ◽  
Author(s):  
Florence Vallelian ◽  
Raphael M. Buzzi ◽  
Marc Pfefferlé ◽  
Ayla Yalamanoglu ◽  
Irina L. Dubach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Sickle Cell Disease ◽  
Bone Marrow Cells ◽  
Cell Disease ◽  
Secondary Immunodeficiency ◽  
Gm Csf ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

AbstractHeme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias, such as sickle cell disease. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Since chronic heme-stress is noxious for macrophages, erythrophagocytes in the spleen are continuously replenished from bone marrow-derived progenitors. Here, we hypothesized that adaptation to heme stress progressively shifts differentiation trajectories of bone marrow progenitors to expand the capacity of heme-handling monocyte-derived macrophages at the expense of the homeostatic generation of dendritic cells, which emerge from shared myeloid precursors. This heme-induced redirection of differentiation trajectories may contribute to hemolysis-induced secondary immunodeficiency. We performed single-cell RNA-sequencing with directional RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation of bone marrow cells towards antioxidant, iron-recycling macrophages, suppressing the generation of dendritic cells in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific CD4 T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype of macrophage expansion with concurrent dendritic cell depletion was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning of hemolytic stress as a driver of hyposplenism-related secondary immunodeficiency.

scholarly journals Vaccine Efficacy after Rituximab Exposure: First Interim Analysis of Virtue Project on Behalf of West Midlands Research Consortium, UK

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 196-196
Author(s):  
Adrian M Shields ◽  
Srinivasan Venkatachalam ◽  
Shankara Paneesha ◽  
Mark Ford ◽  
Tom Sheeran ◽  
...  
Keyword(s):  
B Cell ◽  
Vaccine Efficacy ◽  
Haematological Malignancy ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Spike Glycoprotein ◽  
Secondary Immunodeficiency ◽  
Haematology Patients ◽  
Anti Cd20 ◽  
Kinetics Of

Abstract Background: Anti-CD20 B cell depleting agents are amongst the most commonly used immunotherapeutics employed in the treatment of haematological malignancy and autoimmune diseases. By inducing peripheral B cell aplasia, anti-CD20 depleting agents are hypothesised to significantly impair serological responses to neoantigens, including the SARS-CoV-2 spike glycoprotein within SARS-CoV-2 vaccines. Seropositivity following SARS-CoV-2 is the strongest, measurable correlate of protection from severe COVID-19. Understanding the kinetics of B cell reconstitution and vaccine responsiveness following exposure to B cell depleting agents is essential to maximise vaccine efficacy in patients vulnerable to severe COVID-19. Methods: 80 patients with underlying haematological malignancy and 38 patients with underlying rheumatological disease previously treated with anti-CD20 B cell depleting agents were studied following their second dose of a SARS-CoV-2 vaccine (median time to sampling: 46.5d, IQR: 33.8-63.3). Lymphocyte subset (CD4, CD8, CD19, CD56/16) enumeration was performed using 6 colour flow cytometry (BD Trucount). Total anti-SARS-CoV-2 spike glycoprotein antibodies were measured by enzyme-linked immunosorbent assay (The Binding Site, Human Anti-IgG/A/M SARS-CoV-2-ELISA). The relationship between immune reconstitution following B cell depletion and vaccine responsiveness was explored. Results: In the haematology cohort (median age 70y, IQR 60.3-76.0, 62.5% male), overall seropositivity following vaccination was 60.0%. Individuals on active chemotherapy had significantly lower seroprevalence than those vaccinated following the completion of chemotherapy (22.7% vs 74.1%, p<0.0001). In the rheumatology cohort (median age 65y, IQR 58.3-70.8, 39.9% male), overall seropositivity was 69.4%. In both cohorts, vaccine non-responders had significantly smaller populations of peripheral CD19+ B cells (haematology: 0.20 vs 0.02 x10 9/L, p=0.004, rheumatology: 0.07 vs 0.01 x10 9/L, p=0.03). The magnitude of the antibody response following vaccination did not differ between recipients of Tozinameran and Vaxzeveria in either cohort. Vaccine responsiveness was lower in the first 6 months following B cell depletion therapy; 42.9% in the haematology cohort and 33.3% in the rheumatology cohort, increasing to 100% and 75% respectively in individuals receiving their second dose 6-12 months following B cell depletion (Figure 1). B cell reconstitution in the 7-12 month window following B cell depletion was faster in haematology compared to rheumatology patients (77.8% v 22.2% achieving normal B cell count, p=0.005) and associated with improved vaccine responsiveness. However, persistent immunodeficiency occurred in some haematology patients following completion of treatment: 25% of patients who had completed therapy at least 36 months previously failed to respond to vaccination. In this cohort of vaccine non-responders, 83.3% of individuals had B cell numbers within the normal range. These patients had all previously been treated for follicular lymphoma suggesting a specific mechanism for long-range secondary immunodeficiency in these patients. Conclusions: Serological responsiveness to SARS-CoV-2 vaccines is poor during active chemotherapy for haematological malignancy and in the first 6 months following B cell depletion, regardless of underlying disease. Vaccine responsiveness significantly improves in the 7-12 month window following B cell depletion. Compared to haematology patients, B cell reconstitution is slower in rheumatology patients and associated with reduced vaccine responsiveness, possibly due to the use of additional concurrent disease-modifying anti-rheumatic therapies. Furthermore, long-term secondary immunodeficiency occurs in a minority of haematology patients. To maximise the efficacy from SARS-CoV-2 booster vaccination and optimal utilisation of available vaccine doses, immunisations should be delivered at least 6 months following the administration of anti-CD20 depleting drugs. Figure 1: Kinetics of return of vaccine responsiveness following B cell depletion in haematology and rheumatology patients. Figure 1 Figure 1. Disclosures Paneesha: Roche: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; AbbVie: Honoraria; Celgene: Honoraria. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company.

scholarly journals Rapidly Increasing SARS-CoV-2 Neutralization by Intravenous Immunoglobulins Produced from Plasma Collected During the 2020 Pandemic

2021 ◽  
Author(s):  
Maria R. Farcet ◽  
Michael Karbiener ◽  
Julia Schwaiger ◽  
Reinhard Ilk ◽  
Thomas R. Kreil
Keyword(s):  
Neutralizing Antibodies ◽  
Intravenous Immunoglobulins ◽  
Secondary Immunodeficiency ◽  
Positive Results

AbstractImmunoglobulin (IG) lots (N=176) released since March 2020 were tested for SARS-CoV-2 neutralizing antibodies, with first positive results for September 2020 lots, mean = 1.8 IU/ml, 46% of lots positive. From there, values steadily increased, in correlation with the cumulative COVID-19 incidence, to reach a mean of 36.7 IU/ml and 93% of lots positive by January 2021. Extrapolating the correlation, IGs could reach an anti-SARS-CoV-2 potency of ~400 IU/ml by July 2021. At that stage, prophylactic IG treatment for primary/secondary immunodeficiency could contain similar doses of anti-SARS-CoV-2 as convalescent plasma which is used for treatment of COVID-19.

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