Subject(s)
Autoimmunity/genetics , CD3 Complex/deficiency , Immunologic Deficiency Syndromes/genetics , Antibodies/immunology , B-Lymphocytes/immunology , CD3 Complex/genetics , CD3 Complex/immunology , Child, Preschool , Fatal Outcome , Female , High-Throughput Nucleotide Sequencing , Humans , Immunologic Deficiency Syndromes/immunology , Infant , Killer Cells, Natural/immunology , Mutation, Missense , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunologyABSTRACT
The ongoing outbreak of COVID-19 has been announced by the World Health Organization as a worldwide public health emergency. The aim of this study was to distinguish between severe and non-severe patients in early diagnosis. The results showed that the mortality of COVID-19 patients increased accompanied by age. Host factors CRP, IL-1ß, hs-CRP, IL-8, and IL-6 levels in severe pneumonia patients were higher than in non-severe patients. CD3, CD8, and CD45 counts were decreased in COVID-19 patients. The results of this study suggest that the K-values of CD45 might be useful in distinguishing between severe and non-severe cases. The cut-off value for CD45 was -94.33. The K-values for CD45 in non-severe case were above the cut-off values, indicating a 100% prediction success rate for severe and non-severe cases following SARS-CoV-2 infection. The results confirmed that immune system dysfunction is a potential cause of mortality following COVID-19 infection, particularly for the elderly. CD45 deficiency dysfunction the naïve and memory T lymphocytes which may affects the long-term effectiveness of COVID-19 vaccines. K-values of CD45 might be useful in distinguishing between severe and non-severe cases in the early infection. May be CD45 could increase the diagnostic sensitivity.
Subject(s)
Betacoronavirus/immunology , CD3 Complex/deficiency , Coronavirus Infections/immunology , Host-Pathogen Interactions/immunology , Leukocyte Common Antigens/deficiency , Pneumonia, Viral/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Early Diagnosis , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Young AdultABSTRACT
Autoimmune regulator (AIRE) mutations result in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome characterized by defective central T cell tolerance and the production of many autoantibodies targeting tissue-specific antigens and cytokines. By studying CD3- and AIRE-deficient patients, we found that lack of either T cells or AIRE function resulted in the peripheral accumulation of autoreactive mature naïve B cells. Proteomic arrays and Biacore affinity measurements revealed that unmutated antibodies expressed by these autoreactive naïve B cells recognized soluble molecules and cytokines including insulin, IL-17A, and IL-17F, which are AIRE-dependent thymic peripheral tissue antigens targeted by autoimmune responses in APECED. AIRE-deficient patients also displayed decreased frequencies of regulatory T cells (Tregs) that lacked common TCRß clones found instead in their conventional T cell compartment, thereby suggesting holes in the Treg TCR repertoire of these patients. Hence, AIRE-mediated T cell/Treg selection normally prevents the expansion of autoreactive naïve B cells recognizing peripheral self-antigens.
Subject(s)
Autoantibodies/immunology , Autoimmunity/genetics , B-Lymphocytes/immunology , Polyendocrinopathies, Autoimmune/immunology , Transcription Factors/deficiency , Adolescent , Autoantibodies/blood , Autoantibodies/metabolism , Autoantigens/immunology , B-Lymphocytes/metabolism , CD3 Complex/deficiency , CD3 Complex/genetics , CD3 Complex/immunology , Child , Child, Preschool , Cytokines/immunology , Female , Humans , Immune Tolerance/genetics , Lymphocyte Activation/genetics , Male , Middle Aged , Mutation , Polyendocrinopathies, Autoimmune/blood , Polyendocrinopathies, Autoimmune/genetics , Protein Array Analysis , Proteomics/methods , T-Lymphocytes, Regulatory/immunology , Transcription Factors/genetics , Transcription Factors/immunology , AIRE ProteinABSTRACT
Terminal deoxynucleotidyl transferase (TdT)-negative T-cell lymphoblastic lymphoma is a variant of T-cell lymphoblastic lymphoma/T-cell lymphoblastic leukaemia. TdT is a marker of immaturity expressed in 90%-95% cases of lymphoblastic lymphoma and useful in differentiating it from other mature lymphomas/leukaemias. It has been associated with poorer response to chemotherapy and a more aggressive outcome. Here we present a case of TdT-negative T-cell lymphoblastic lymphoma in a 28-year-old man who presented with superior vena cava syndrome. The patient was treated with hyper-cyclophosphamide,vincristine, Adriamycin, dexamethasone (CVAD), however unfortunately suffered a relapse 1 year later. A unique feature of our case was that on relapse, the patient lost expression of the T-cell lineage-specific marker CD3, which has previously not been reported in association with TdT-negative T-cell lymphoblastic lymphoma. The patient failed to respond to chemotherapy on his relapse and died.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CD3 Complex/deficiency , DNA Nucleotidylexotransferase/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Adult , Biomarkers/metabolism , Fatal Outcome , Humans , Male , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , RecurrenceABSTRACT
The present study, performed in Dahl salt-sensitive (SS) and SS- Rag1-/- rats lacking T and B lymphocytes, tested the hypothesis that immune cells amplify salt-sensitive hypertension and kidney damage in response to a high-protein diet. After being weaned, SS and SS- Rag1-/- rats were placed on an isocaloric, 0.4% NaCl diet containing normal (18%) or high (30%) protein. At 9 wk of age, rats were switched to a 4.0% NaCl diet containing the same amount of dietary protein and maintained on the high-salt diet for 3 wk. After being fed the high-salt diet, SS rats fed high protein had amplified hypertension and albumin excretion (158.7 ± 2.6 mmHg and 140.8 ± 16.0 mg/day, respectively, means ± SE) compared with SS rats fed normal protein (139.4 ± 3.6 mmHg and 69.4 ± 11.3 mg/day). When compared with the SS rats, SS- Rag1-/- rats fed high protein were protected from exacerbated hypertension and albuminuria (142.9 ± 5.8 mmHg and 66.2 ± 10.8 mg/day). After 3 wk of the high-salt diet, there was a corresponding increase in total leukocyte infiltration (CD45+) in the kidneys of both strains fed high-protein diet. The SS- Rag1-/- rats fed high-protein diet had 74-86% fewer CD3+ T lymphocytes and CD45R+ B lymphocytes infiltrating the kidney versus SS rats, but there was no difference in the infiltration of CD11b/c+ monocytes and macrophages, suggesting that the protective effects observed in the SS- Rag1-/- rats are specific to the reduction of lymphocytes. With the SS- Rag1-/- rats utilized as a novel tool to explore the effects of lymphocyte deficiency, these results provide evidence that adaptive immune mechanisms contribute to the exacerbation of salt-induced hypertension and renal injury mediated by increased dietary protein intake.