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1.
Transfus Clin Biol ; 28(3): 264-270, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33901641

ABSTRACT

OBJECTIVES: The patients with hematological malignancies are a vulnerable group to COVID-19, due to the immunodeficiency resulting from the underlying disease and oncological treatment that significantly impair cellular and humoral immunity. Here we report on a beneficial impact of a passive immunotherapy with convalescent plasma to treat a prolonged, active COVID-19 infection in a patient with a history of nasopharyngeal diffuse large B-cell lymphoma treated with the therapy inducing substantial impairment of particularly humoral arm of immune system. The specific aim was to quantify SARS-CoV2 neutralizing antibodies in a patient plasma during the course of therapy. MATERIALS AND METHODS: Besides the standard of care treatment and monitoring, neutralizing antibody titers in patient's serum samples, calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human), were quantified in a time-dependent manner. During the immunotherapy period peripheral blood flow cytometry immunophenotyping was conducted to characterize lymphocyte subpopulations. RESULTS: The waves of clinical improvements and worsening coincided with transfused neutralizing antibodies rises and drops in the patient's systemic circulation, proving their contribution in controlling the disease progress. Besides the patient's lack of own humoral immune system, immunophenotyping analysis revealed also the reduced level of helper T-lymphocytes and immune exhaustion of monocytes. CONCLUSION: Therapeutic approach based on convalescent plasma transfusion transformed a prolonged, active COVID-19 infection into a manageable chronic disease.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19/therapy , Immunocompromised Host , Lymphoma, Large B-Cell, Diffuse/complications , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/blood , Antibodies, Viral/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Chlorocebus aethiops , Combined Modality Therapy , Hematopoietic Stem Cell Transplantation , Humans , Immunization, Passive , Immunophenotyping , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/immunology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphopenia/etiology , Lymphopenia/immunology , Male , Middle Aged , Monocytes/immunology , Nasopharynx/virology , RNA, Viral/analysis , RNA, Viral/blood , Radiotherapy, Adjuvant , Rituximab/administration & dosage , Rituximab/adverse effects , SARS-CoV-2/isolation & purification , Vero Cells , Virus Cultivation , COVID-19 Serotherapy
2.
Scand J Immunol ; 72(5): 434-43, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21039738

ABSTRACT

Essential part of a response to infection is early pathogen recognition and adequate initiation of innate immunity. One of the hallmarks of systemic lupus erythematosus (SLE) is reduced resistance to infection despite overall hyperactivity of the immune system. Immunosuppressive drugs (high-dose corticosteroids and cytotoxic agents) are independent risk factors for infection in SLE, with bacteria as predominant cause. To investigate whether less aggressive immunomodulatory treatment may still affect recognition and response to Gram-negative bacteria, we measured TLR4 expression in monocytes of untreated SLE patients and patients on chloroquine and low-dose steroid therapy and examined the drugs' influence on monocyte TLR4 expression in peripheral blood mononuclear cell (PBMC) culture. Additionally, we determined whether induction of monocyte NF-κB signalling, TNF-α and IL-6 production with lipopolysaccharide (LPS), a TLR4 ligand, can be altered with dexamethasone, chloroquine or both. There was no statistically significant difference in TLR4 expression between patients with SLE and controls, even though treated SLE patients tended to have lower frequency of TLR4(+) monocytes and TLR4 mean fluorescence intensity than healthy controls. However, neither dexamethasone nor chloroquine had major influence on TLR4 expression in vitro or suppressed LPS-induced NF-κB activation in monocytes, although dexamethasone decreased TNF-α and IL-6 production. Therefore, even if low-dose steroids or chloroquine do not seem to affect TLR4 expression and signalling, steroids might decrease cytokine production in response to LPS.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Chloroquine/pharmacology , Lipopolysaccharides/pharmacology , Monocytes/drug effects , Adrenal Cortex Hormones/therapeutic use , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Cells, Cultured , Chloroquine/therapeutic use , Dexamethasone/pharmacology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-6/metabolism , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/metabolism , Monocytes/cytology , Monocytes/metabolism , NF-kappa B/metabolism , Phosphorylation/drug effects , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
3.
Haematologica ; 85(12): 1261-7, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11114132

ABSTRACT

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether expression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with hematologic indices and tumor load in the disease. Furthermore, the change of Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied. DESIGN AND METHODS: In 42 B-CLL patients, of whom 13 were sequentially monitored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp epitopes on peripheral blood lymphocytes was determined by flow cytometry analysis and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. RESULTS: Median RMF values in B-CLL patients were higher than in age-matched controls. Pgp expression did not correlate with any of the hematologic features or clinical stage of the disease. Patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both measured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in comparison to those of non-treated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after treatment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders. This was in contrast to unchanged or even increased RMF values in those patients who did not respond to therapy. INTERPRETATION AND CONCLUSIONS: Our study confirms the importance of quantitative evaluation of Pgp expression by flow cytometry. At the clinical level, cross-sectional, single test evaluation of Pgp is of limited value whereas sequential follow-up values correlate with treatment response.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , B-Lymphocytes/metabolism , Drug Resistance, Multiple , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Age Factors , Aged , B-Lymphocytes/pathology , Drug Resistance, Multiple/genetics , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Male , Matched-Pair Analysis , Middle Aged , Treatment Outcome
4.
Clin Exp Immunol ; 121(2): 332-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10931150

ABSTRACT

Acute RSV infection in infancy may produce some asthma-like symptoms and may be followed by a recurrent wheeze later in childhood. It has been proposed that RSV infection stimulates type-2 cytokine responses, resembling those found in atopy and asthma. Peripheral blood cells were obtained from RSV-infected infants (n = 30) and healthy controls (n = 10). After in vitro restimulation of the cells, intracellular IL-4 and interferon-gamma (IFN-gamma) were measured by flow cytometry. The cells from RSV-infected infants produced more IL-4 and less IFN-gamma than those from healthy controls. IL-4 production was more frequent in CD8 than in CD4 cells, and the bias toward IL-4 production was greatest in infants with mild infections, whereas IFN-gamma production increased with disease severity. Our conclusions are that RSV infection is associated with IL-4 production in peripheral T cells, and that peripheral blood in infants with severe disease may be depleted of cytokine-producing cells.


Subject(s)
Flow Cytometry , Interferon-gamma/blood , Interleukin-4/blood , Respiratory Syncytial Virus Infections/immunology , Th2 Cells/immunology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Lymphocyte Activation , Male , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/isolation & purification , Th2 Cells/metabolism
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