Tests

CD-Cells-Immunity

Based on the current literature, CD57+ cells are a prognostic laboratory parameter during and after the treatment of chronic Lyme disease.

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The examination of the immune status with CD3+/CD56+/CD57+ and CD19+ cells

The examination of the immune status is crucial, especially in cases of suspected viral, bacterial, or chronic infections, as well as in immune deficiencies. Analyzing the cellular immune response through CD3+/CD56+/CD57+ NK cells provides important insights into the current health status. Similarly, determining the CD19+ B lymphocytes offers detailed insight into the humoral immune system. These two parameters provide valuable information about the immune system and aid in the diagnosis and treatment of various diseases. Below, the functions and significance of these cells, as well as their clinical relevance, will be further explained.


Development and function of T cells and natural killer cells

Lymphocytes develop from precursor cells located in the bone marrow. B cells originate from the bone marrow and natural killer (NK) cells migrate directly to the periphery from there. T cells, however, migrate from the bone marrow to the thymus, where they undergo positive and negative selection. They develop into naive T cells, which have not yet encountered antigens, and patrol between blood and lymphatic tissues. Natural killer T cells are another T-cell lineage that develops in the thymus and has a receptor, in addition to the T-cell receptor, that recognizes glycolipid antigens of bacterial origin.

T cells (CD3+ lymphocytes) recognize antigens by means of their T cell receptor and the cofactor CD3 and induce or regulate the innate immune defense. T cells are increased in viral (e.g. rubella) and bacterial (in the overcoming phase) infections as well as fungal infections (e.g. pneumocystis, candida), typhoid, T-cell leukemia and lymphomas and in smokers. Reduced T-cells are found in congenital (DiGeorge syndrome, SCID, Wiskott-Aldrich syndrome, Ataxia teleangiektasia/LouisBar syndrome) and acquired (malignant diseases, infectious diseases, e.g. AIDS, tuberculosis), immune defects, after radiation and medication with immunsuppressants (e.g. e.g. glucocorticoids), cytostatics or steroids, in chronic liver diseases (e.g. liver cirrhosis, alcohol-related and non-alcohol-related steatohepatitis, hepatitis C), burns, SLE and other autoimmune diseases, Cushing's syndrome, renal failure and iron deficiency anemia.

Role of T cells (CD3+ lymphocytes) and NK cells (CD3-CD16+/CD56+/CD57+) in the immune system and their clinical significance.

T cells (CD3+ lymphocytes) recognize antigens through their T-cell receptor and the co-factor CD3, inducing or regulating cellular immune responses. Elevated T cells are observed in viral (e.g., rubella) and bacterial (during recovery phase) infections, as well as fungal infections (e.g., Pneumocystis, Candida), typhoid fever, T-cell leukemias, and lymphomas, as well as in smokers. Reduced T cells are found in congenital (DiGeorge syndrome, SCID, Wiskott-Aldrich syndrome, Ataxia telangiectasia/Louis-Bar syndrome) and acquired (malignant diseases, infectious diseases, e.g., AIDS, tuberculosis) immunodeficiencies, following radiation exposure, and medication with immunosuppressants (e.g., glucocorticoids), cytostatics, or steroids, in chronic liver diseases (e.g., liver cirrhosis, alcohol-related and non-alcohol-related steatohepatitis, hepatitis C), burns, SLE, and other autoimmune diseases, Cushing's syndrome, renal insufficiency, and iron deficiency anemia.

Natural killer cells (NK cells, CD3+/CD16+/CD56+/CD57+) are effector cells of the innate immune system. They kill tumor cells and virus-infected body cells by inducing their apoptosis. Elevated NK cells are observed in viral infections, mycoplasma infections, or after drug-related immune stimulation, as well as in NK cell leukemia (rare). Decreased NK cells are found in progressive tumor growth, in smokers, during physical exercise, and during a low-calorie diet.

CD57+ cells, as a subset of NK cells, can be increased in chronic viral infections such as CMV, HIV, Hepatitis C, and Epstein Barr virus.

CD19 lymphocytes

B-lymphocytes are essential in specific immune responses. In this process, B lymphocytes control the antibody-based defence response of the body.

Via immunoglobulins (Ig) on the cell surface, B lymphocytes can recognize specific antigens. These antigens are proteins foreign to the body.

In addition to immunoglobulins, B lymphocytes have other markers on the membrane surface that are used to identify subtypes of B cells (lymphocyte differentiation). The most common surface markers of B lymphocytes are CD19, CD20 and CD21.

Structure and regulation of CD19 expression

CD19 as a 95-kDa member of the immunoglobulin super-family expressed exclusively on B lymphocytes is classified as a type I transmembrane protein, with a single transmembrane domain with a cytoplasmic C-terminus, and extracellular N-terminus. CD19 is a critical co-receptor for B cell antigen receptor (BCR) signal transduction. The surface density of CD19 is highly regulated throughout B cell development and maturation, until the loss of expression during terminal plasma cell differentiation. CD19 expression in mature B cells are 3-fold higher than that found in immature B cells, with slightly higher expression in B1 cells than in B2 (conventional B) cells.

CD19 as a marker for the humoral immune response

B cells (CD19 lymphocytes) are a subgroup of lymphocytes and can be measured quantitatively in the blood as part of leukocyte typing (determination of immune status). The B cells fulfil their function within the framework of the so-called humoral immune system (production of antibodies).

The importance of the CD19 marker is that it allows analysis of B lymphocytes, which are responsible for humoral immune responses.

CD19 is one of the most reliable surface biomarkers for B lymphocytes they have an important role in the normal expansion and function of the peripheral B-cell pool. It contributes to maintaining the balance between humoral, antigen-induced response and tolerance induction, as even small modulations in CD19 expression can impact B cell signalling thresholds and dramatically affect the sensitivity and specificity of B cell mediated immunity.

Interpretation of CD19 values in the context of B-cell functions

  • High numbers of the absolute B-Cells CD19+ can be sign of general B-cell lymphocytes stimulation: current virus infection (EBV-Early Infection), recent infection with bacteria, autoimmune disease, lymphadenopathy.
  • Low numbers of the absolute B-Cells CD19+ can be sign of general B-cell lymphocytopenia: cellular immunodeficiencies, stressful situations, therapies with cortisone or with B-cell depleting antibodies. Chemotherapies, radiation therapies, infections with pathogens that damage the immune system and higher levels of mycotoxins biomarkers can be the reason for low CD19.

Additional information about CD cells

CD57+ cells document the extent of immunosuppression in chronic Borrelia infections. According to current literature, CD57+ cells are thus a prognostic laboratory parameter during and after the treatment of chronic Borrelia infections. Clinical research and case studies have shown that chronic Borrelia infections are accompanied by changes in cellular immune response. Evidence for this includes a reduced number of natural killer cells (NK/CD3-CD56+), especially a lower absolute number of activated natural killer cells (CD3-CD56+CD57+). While acute Borrelia burgdorferi infections and other diseases show normal CD57 parameters, patients with chronic Borrelia infections often have fewer than 100 CD57+ cells per microliter. According to scientific studies, a reduced absolute number of CD57+ cells was primarily observed in patients whose nervous system was affected. Patients with musculoskeletal complaints were more likely to have normal CD57+ cells. The reduced number of CD57 cells persists until an improvement in symptoms is achieved through antibiotic treatment or other forms of therapy.

Elderly patients with underlying medical conditions such as high blood pressure, heart problems, or diabetes, cancer, another active infection, and/or individuals with immunosuppression may have a higher likelihood of experiencing a more severe course of COVID-19 [1],[2],[3],[4]. Therefore, in suspected cases, we recommend additional evaluation of the cellular (CD3+) and natural killer cell (CD56+/CD57+) immune status.

Acute viral infections, chronic viral infections, bacterial infections, immunodeficiencies, immunostimulation

Viral infections, bacterial infections, fungal infections, parasitosis, allergies, iron deficiency, liver diseases (caused by toxins including mycotoxins), autoimmune diseases, neurodermatitis, elevated lymphocyte levels, decreased lymphocyte levels

References:

[1] Okba et al. medRxiv 2020.03.18.20038059; doi: 10.1101/2020.03.18.20038059; [2] Risk of COVID-19 for patients with cancer; Hanping Wang, Li Zhang; Published:March 03, 2020 [3] The Novel Coronavirus Disease (COVID-19) Threat for Patients with Cardiovascular Disease and Cancer; Sarju Ganatra, MD, Sarah P. Hammond, MD, Anju Nohria, MD; 18 March 2020 [4] T.M. Rickabaugh, R.D. Kilpatrick, L.E. Hultin et al.: The dual Impact of HIV-1 infection and aging on naïve CD4+ T-cells: additive and distinct patterns of impairment. PLoS One, 2011, 6(1) e16459. S. Kohler, A. Thiel: Life after the thymus: CD31+ and CD31- human naïve T cell subsets. Blood, 2009, 113(4): 769-74 A. Stelmaszczyk-Emmel, A. Zawadzka-Krajewska, A-Szypowska et al.: Frequency and Activation of CD4+CD25highFoxP3+ regulatory T cells in peripheral blood from children with atopic allergy. Int Arch Allery Immunol, 2013, 162(1): 16-24. A. Boleslawski, S.B. Othman, L. Aoudjehane et al.: CD28 expression by peripheral blood lymphocytes as a potential predictor of the development of de novo malignancies in long-term survivors after liver transplantation. Liver Transpl, 2011, 17(3): 299-305. 5. V. Appay, R.A. van Lier, F. Sallusto et al.: Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A, 2008, 73(11): 975-83. C.M. Nielsen, M.J. White, M.R. Goodier, E.M. Riley, Functional siginificance of CD57 expression on human NK cells and relevance to disease, Front Immunol. 2013; 4: 422