Purine nucleoside phosphorylase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The severe combined immunodeficiency may be clinically indistinguishable from adenosine deaminase deficiency; lymphopenia, thymic deficiency and infections; hypouricemia; and deficient activity of purine nucleoside phosphorylase (PNP). The abnormality in purine metabolism in purine nucleoside phosphorylase deficiency resembles that of adenosine deaminase deficiency in that each leads to the accumulation of nucleosides and deoxynucleosides. Deficiency of PNP is unique among immunodeficiencies in that patients have impressive hypouricemia and a very low level of excretion of uric acid in the urine. In PNP, deficiency transfusion therapy has variously been reported to produce partial improvement or no improvement in immune function. In an extensive experience with 100 weeks of erythrocyte transfusion therapy in a boy with PNP deficiency, there was a correction of the elevated level of deoxyguanine triphosphate in erythrocytes and leukocytes, as well as a substantial increase in serum concentrations of urate and decrease in urinary nucleoside content.
The Immune System During HIV-1 Infection
Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts in Retroviral Testing, 2020
As with most infectious agents, the human body responds to HIV infection by producing antibodies. These antibodies are usually produced between 6 and 12 weeks following infection, although in rare cases they may not be detected for months or years. Alternatively, a decrease in antibody production may occur as the immune system becomes less responsive. Viral replication usually occurs late in the disease and is accompanied by disease symptoms (i.e., the AIDS syndrome becomes evident). As HIV infection progresses, a general lymphopenia (decrease in lymphocytes in the blood) occurs. Cell-to-cell communication is an important part of the normal homeostatic mechanism of cell-mediated immunity (CMI). Control and coordination of CMI is achieved through the action of plurifunctional protein mediators known as cytokines. In general, specific monoclonal antibodies made against a specific antigen present on the cells, such as the CD4 molecule, are labeled with a fluorochrome.
Host Immune Response vs. COVID-19
Ahmed Al-Harrasi, Saurabh Bhatia in Role of Essential Oils in the Management of COVID-19, 2022
Advancement in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid increase in infected patients worldwide. Due to the varied immune response against SARS-CoV-2 from individual to individual, it’s important to understand host immune response against SARS-CoV-2 more deeply, especially to understand its role in disease pathogenesis and clinical manifestations. Coronavirus not only stimulates host antiviral immune-mediated pathways but can also trigger hyper-inflammatory responses represented by significant production in pro-inflammatory cytokines in patients with severe COVID-19, resulting in lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. Thus, dysfunction of various molecular or signaling pathways that leads to immune abnormalities in COVID-19 patients should be revealed in order to deeply understand the host–pathogen interaction and for the early recognition of this immunological phenotype. This will help in the quick identification of patients who can progress to severe disease. This chapter will give an overview of the immunopathology of COVID-19, its potential mechanisms, and clinical implications.
Impaired lymphocyte reconstitution after autologous transplant is associated with apoptosis of CD8+ T cells and adverse clinical outcome
Published in Leukemia & Lymphoma, 2019
Uri Rozovski, Ella Naparstek, Shani Frank, Alexey Fourman, Eti Zigman-Hoffman, Margalit Bleiberg, Moshe Yeshurun, Svetlana Trestman, Boris Tartakovsky
We noticed that the lymphocyte counts, after autologous hematopoietic stem cell transplantation, oscillated during the first 4 post-transplant months. Thereafter, the lymphocyte counts stabilized and segregated the patients into two groups, those who normalized their lymphocyte counts and those with prolonged lymphopenia. In both groups, the CD4 counts remained low for at least 6 months. However, in approximately half of the patient, the CD8 counts increased to normal or above normal values. Patients with prolonged lymphopenia had higher rates of lymphocytes’ spontaneous apoptosis and the lymphocytes in patients who restored their counts expressed the intracellular CD14-derived MO2 epitope that protects the cells from apoptosis. These findings were translated to longer disease-free survival and overall survival in patients who restored the CD8 counts. Collectively, our data show that post-transplant lymphocytes that express intracellular CD14-MO2 epitope have survival advantage.
Lymphopenia predicts preclinical relapse in the routine follow-up of patients with diffuse large B-cell lymphoma
Published in Leukemia & Lymphoma, 2015
Xiaolei Wei, Yongqiang Wei, Fen Huang, Hui Jing, Muchen Xie, Xiaoxiao Hao, Ru Feng
The absolute lymphocyte count (ALC) has been reported to predict relapse in diffuse large B-cell lymphoma (DLBCL). We performed the present study to determine whether the ALC could identify preclinical relapse during routine follow-up. Among all 148 patients analyzed, 39 patients exhibited relapse. Patients without relapse had a higher ALC compared with those with proven relapse at the time of relapse as well as 1 and 3 months before relapse. Low ALC (< 950/μL) at 1 and 3 months before relapse had a positive predictive value of 74.2% and 69.0% and a negative predictive value of 86.3% and 84.0%, respectively, to predict relapse. Low ALC at both 1 and 3 months before relapse was significantly associated with relapse by univariate and multivariate analysis. Our data suggest the potential of lymphopenia to detect preclinical relapse in DLBCL. This may help to identify patients requiring salvage chemotherapy at the time of minimal disease rather than clinically overt relapse.
Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients
Published in OncoImmunology, 2012
Manuarii Manuel, Olivier Tredan, Thomas Bachelot, Gilles Clapisson, Anais Courtier, Gilles Parmentier, Tioka Rabeony, Audrey Grives, Solène Perez, Jean-François Mouret, David Perol, Sylvie Chabaud, Isabelle Ray-Coquard, Intidhar Labidi-Galy, Pierre Heudel, Jean-Yves Pierga, Christophe Caux, Jean-Yves Blay, Nicolas Pasqual, Christine Ménétrier-Caux
Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called “divpenia” (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients’ medical care.
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