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עמוד בית
Sat, 25.05.24

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July 2022
March 2021
Laura A. Montiel-Cervantes DSc, Gabriela Medina MSc, María Pilar Cruz-Domínguez DSc, Sonia-Mayra Pérez-Tapia DSc, María C. Jiménez-Martínez DSc, Hugo-Iván Arrieta-Oliva DSc, Gregorio Carballo-Uicab DSc, Laura López-Pelcastre MD, and Rosa Camacho-Sandoval DSc

Background: Immune cell counts in blood in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be useful prognostic biomarkers of disease severity, mortality, and response to treatment.

Objectives: To analyze sub-populations of lymphocytes at hospital admission in survivors and deceased from severe pneumonia due to coronavirus disease-2019 (COVID-19).

Methods: We conducted a cross-sectional study of healthcare workers confirmed with SARS-CoV-2 in convalescents (control group) and healthy controls (HC) diagnosed with severe COVID-19. Serum samples were taken at hospital admission and after recovery. Serum samples ≥ 25 days after onset of symptoms were analyzed for lymphocyte subpopulations through flow cytometry. Descriptive statistics, Kruskall-Wallis test, receiver operating characteristic curve, calculation of sensitivity, specificity, predictive values, and Kaplan-Meier analysis were performed.

Results: We included 337 patients: 120 HC, 127 convalescents, and 90 severe COVID-19 disease patients (50 survivors, 40 deceased). For T cells, total lymphocytes ≥ 800/μL, CD3+ ≥ 400/μL, CD4+ ≥ 180/μL, CD8+ ≥ 150/μL, B cells CD19+ ≥ 80/μL, and NK ≥ 34/μL subsets were associated with survival in severe COVID-19 disease patients. All subtypes of lymphocytes had higher concentrations in survivors than deceased, but similar between HC and convalescents. Leukocytes ≥ 10.150/μL or neutrophils ≥ 10,000/μL were associated with increased mortality. The neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5 increased the probability of death in severe COVID-19 (odds ratio 11.68).

Conclusions: Total lymphocytes; NLR; and levels of CD3+, CD4+, CD8+, and NK cells are useful as biomarkers of survival or mortality in severe COVID-19 disease and commonly reach normal levels in convalescents.

December 2016
Yael Shahal-Zimra PhD, Zohar Rotem MSc, Judith Chezar PhD, Tzippy Shochat MSc, Liron Ross MSc, Itai Pickholtz PhD and Esther Rabizadeh PhD

Background: Reference ranges for adult peripheral blood lymphocyte subsets have been established in a few countries. To the best of our knowledge no broad lymphocyte subset analysis of the Israeli population has been reported. 

Objectives: To establish reference ranges for healthy adults in Israel and to describe age- and gender-specific differences, if present.

Methods: Lymphocyte subsets CD3, CD3/CD4, CD3/CD8, CD3-/CD16+/CD56+, CD3/TCRαβ, CD3/TCRγδ, and CD19 were examined by flow cytometry in 326 subjects. Samples were subdivided according to age and gender.

Results: Women of all ages had a significantly higher percentage and absolute counts of CD3/CD4 cells than their male counterparts. Higher CD3/CD4 cells were observed also in the older population (> 50 years). CD3/CD8 and CD3-/CD16+/CD56+ were higher in males. Older males had a lower total lymphocyte percentage and CD19 cells compared to younger men. No significant gender-related differences were observed in percent and number of CD19, CD3/TCRαβ or CD3/TCRγδ at all ages.

Conclusions: These reference values could be useful in further studies for assessing changes that occur in different populations in human pathology.


September 2016
Lazaros I. Sakkas MD DM PhD (London) FRCP (London) and Dimitrios P Bogdanos MD PhD (London)

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 


September 2015
Inbal Mayan MD, Raz Somech MD PhD, Atar Lev MSc, Avner H. Cohen, Naama W. Constantini MD and Gal Dubnov-Raz MD MSc

Background: Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections (URI). T lymphocytes have a major anti-viral role, are affected by vitamin D metabolism, and may mediate the link between vitamin D and URIs. Competitive swimmers have a relatively high rate of URIs, alongside a high prevalence of low vitamin D concentration. 

Objectives: To examine the associations linking T cell receptor excision circles (TREC, markers of thymus activity), circulating 25(OH)D concentrations and the effect of vitamin D supplementation, and URI symptoms in young competitive swimmers.

Methods: We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency. Randomized supplementation of either vitamin D3 or placebo was given for 12 winter weeks. URI symptoms were recorded weekly. The associations between TREC copy numbers, vitamin D and URI burden were examined.

Results: TREC concentrations decreased with the participants’ age (r = -0.346, P = 0.003), with no significant between-gender difference. TREC concentrations did not materially differ among subjects with normal, insufficient or deficient vitamin D status, and were not affected by vitamin D supplementation. No significant correlations were found between TREC levels or their changes during the study period, and mean URI severity or duration. 

Conclusions: Thymus activity, represented by higher TREC levels, was not related to vitamin D concentrations or status, and was not affected by vitamin D supplementation in adolescent swimmers. TREC concentrations were not associated with URI severity or duration in this population.


August 2012
S. Bezalel, I. Asher, D. Elbirt and Z.M. Sthoeger

Current treatments for systemic lupus erythematosus (SLE) are effective in reducing morbidity and mortality but are not specific and have severe adverse effects. Based on understanding of the different dysregulated immunological pathways involved in SLE pathogenesis, specific targeted therapies were developed. This review presents the current and the near-future novel biological immune targeted treatments, such as B cell-targeted therapy, cytokine blockade, peptide-based treatments and other novel treatments for SLE.

July 2011
N. Sharon, R. Talnir, O. Lavid, U. Rubinstein, M. Niven, Y. First, A.J.I. Tsivion and Y. Schachter
Background: Pandemic influenza A2/H1N1 carries a relatively high morbidity, particularly in young people. Early identification would enable prompt initiation of therapy, thereby improving outcomes.
Objective: To describe the epidemiological, clinical and laboratory characteristics of children admitted to hospital with the clinical diagnosis of influenza with reference to pandemic influenza A/H1N1.
Methods: We conducted a prospective study of all children aged 16 years or less admitted to the pediatric department with the clinical diagnosis of influenza-like illness from July to October 2009. The presence of A/H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain (RT-PCR) analysis of nasopharyngeal secretions. Positive cases were compared with negative cases concerning epidemiological data, risk factors, clinical presentation and laboratory parameters, with emphasis on changes in the differential blood count.
Results: Of the 106 study patients, 53 were positive to influenza A/H1N1 and 53 were negative. In both groups nearly all patients had fever at presentation and approximately two-thirds had both fever and cough. All patients had a mild clinical course, no patient needed to be admitted to the intensive care unit and no mortalities were recorded. Hyperactive airway disease was more common in the A/H1N1-positive group. Pneumonia occurred in 30% of children in both groups. Laboratory findings included early lymphopenia and later neutropenia in the A/H1N1-infected patients.
Conclusions: Leukopenia consisting of lymphopenia and later neutropenia was common in patients with A/H1N1 infection but was not correlated with disease severity or clinical course, which were similar in both groups. However, reduced leukocyte count can be used as an additional criterion for diagnosing A/H1N1 infection until RT-PCR results are available.
March 2006
M.I. Besser. A.J. Treves. O. Itzhaki, I. Hardan, A. Nagler, M.Z. Papa, R. Catane, E. Winkler, B. Shalmon-Sifroni and J. Schachter

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

[1] TIL = tumor-infiltrating lymphocytes 

October 2001
Maurizio Cutolo, MD, Bruno Seriolo, MD, Carmen Pizzorni, MD and Alberto Sulli, MD
January 2000
Shoshana Merchav PhD, Ilana Tatarsky MD, Judith Chezar MD, Rivka Sharon MD, Hanna Rosenbaum MD and Yael Schechter MD

Background: The etiology of bone marrow failure, a prominent feature of paroxysmal nocturnal hemoglobulinuria, is presently unknown.

Objectives: To evaluate the possible influence of cellular immune mechanisms in the bone marrow failure of PNH.

Methods: We studied marrow erythroid colony formation in a patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic marrow complications.

Results: In vitro assays revealed a pronounced inhibition of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes. Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E numbers. Reevaluation of in vitro erythropoiesis during steroid administration indicated a persistent, albeit less prominent, T cell inhibitory effect.

Conclusion: Our findings provide the first direct evidence for a cellular immune inhibitory phenomenon accompanying PNH.


PNH= paroxysmal nocturnal hemoglobinuria

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