Immunodeficiency: Test and Diagnosis

1st-order laboratory parameters–obligatory laboratory testing.

  • Small blood count [leukocytopenia (leukocyte/white blood cell deficiency), thrombocytopenia (platelet/platelet deficiency), if applicable.
  • Differential blood count [possibly lymphopenia (deficiency of lymphocytes), neutropenia (deficiency of neutrophil granulocytes). Lack of monocytes or also an eosinophilia (increase in the number of eosinophilic granulocytes)]
  • Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
  • Serological tests for suspected bacterial, viral or parasitic diseases.

Laboratory parameters 2nd order – depending on the results of the history, physical examination and the obligatory laboratory parameters – for differential diagnostic clarification.

  • Screening for severe combined immunodeficiency (SCID) from dried blood from the first hours of life (48-72 h) to determine the immune status’ [screening for SCID has not yet been included in the Children’s Guideline by the Federal Joint Committee (G-BA)].
  • Immunoglobulins (humoral immunodeficiencies) – gammopathy diagnostics (frequently: IgA, IgG, IgM gammopathy); rarely: IgD, IgE gammopathy) [hypogammaglobulia.]
  • Immunoelectrophoresis – for analysis of plasma proteins; for suspected monoclonal gammopathies.
  • Cellular immune status* * (cellular immunodeficiencies) – lymphocyte differentiation (B cells; T cells; T4 cells; T8 cells; CD4/CD8 ratio; NK cells; activated T cells).
  • Autoantibody addiction testing
  • Liver parameters – alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT), glutamate dehydrogenase (GLDH), and gamma-glutamyl transferase (gamma-GT, GGT).
  • Renal parameters – urea, creatinine, cystatin C or creatinine clearance, as appropriate.
  • Urine status (rapid test for: pH, leukocytes, nitrite, protein, glucose, ketone, urobilinogen, bilirubin, blood), sediment, if necessary urine culture (pathogen detection and resistogram, that is, testing suitable antibiotics for sensitivity / resistance).
  • Tumor markers – depending on the suspected diagnosis.

With inconspicuous basic diagnostics (small blood count, differential blood count, immunoglobulins), a primary immunodeficiency (PID) is largely excluded. If suspicion persists, the patient should be referred to an immunodeficiency center.

Newborn screening (NGS)

  • T-cell receptor excision circles (TREC) – target disease: severe combined immunodeficiency (SCID).
    • Severe combined immunodeficiency (SCID) – group of genetic diseases (autosomal or X-linked recessive genetic defects) characterized by a complete absence of immune defense (inhibition of T-lymphocyte development as well as, possibly. Absence of B-lymphocytes and NK-lymphocytes); untreated, most affected individuals die in infancy; prevalence (disease frequency) about 1:70,000.

Immune status – overview of individual parameters

Granulocytes

  • Neutrophil granulocytes – this subset of granulocytes represents the largest proportion of all circulating leukocytes in the body. The cells produced in the bone marrow remain in the bloodstream for only a few hours and are completely degraded after 1-2 days. In addition to the release of inflammatory mediators, phagocytosis of bacteria is indicated as the main function.
  • Eosinophilic granulocytes – this fraction of granulocytes has as its main function the killing of parasites and thus probably has a synergistic effect with histamine. The production of this cell type also occurs in the bone marrow.
  • Basophilic granulocytes – this population of granulocytes is also synthesized in the bone marrow. However, the task of these cells is still unclear.

Macrophages

  • Macrophages remain in the bloodstream for about a day and then differentiate into tissue macrophages such as Kupffer cells. As can be inferred from the name, the main function of this cell type is the elimination of microorganisms and immune complexes. In addition, macrophages have a huge pool of interleukins and tumor necrosis factors (TNF). Moreover, macrophages are also involved in antigen presentation and may contribute to the development of febrile conditions.

* * Lymphocytes and their subpopulations.

  • Overall, lymphocytes and their associated subsets represent approximately 30% of all leukocytes stored and circulating in the body. A classification of lymphocytes is made into different subgroups based on their different receptor structures. This form of classification is called CD (cluster of differentiation) classification.
  • T-lymphocytes – T-lymphocytes represent the largest subgroup of lymphocytes, accounting for 70% of all lymphocytes. Characteristic of T lymphocytes is the presence of CD3+ receptors. The development of this group of lymphocytes occurs in the thymus until the precursor cells eventually give rise to antigen-recognizing T lymphocytes. The process of antigen recognition occurs in T lymphocytes through the use of a T cell receptor after antigen is presented by monocytes or macrophages, which develop from monocytes.
  • Ts lymphocytes (T suppressor lymphocytes) – This subset is characterized by the presence of CD3+ and CD8+ receptors. The function of this cell type is the suppression of excessive immune reactions. To perform this function requires interaction of Ts lymphocytes with almost all nucleated cells of the human body.
  • Tc lymphocytes – This subset, which possesses CD3+ and CD8+ as well as CD28+ receptors, represents a population of cytotoxic cells. Analogous to Ts lymphocytes, Tc lymphocytes also require communication with nucleated somatic cells to perform their function. The main task of these lymphocytes is the recognition of virus-infected cells. If the Tc lymphocytes encounter an infected body cell, it is immediately eliminated.
  • Th lymphocytes – In order for the various components of the lymphocyte system to be meaningfully activated, the body requires a cell type to coordinate these defense cells. This task is performed by Th lymphocytes, which have CD3+ and CD4+ receptors. Without the presence of this cell type, it is not possible for the Tc lymphocytes, for example, to destroy virus-infected cells. Via the secretion of interleukins (ILs), there is the possibility of stimulating B lymphocytes, macrophages and cytotoxic T cells.
  • B lymphocytes – In addition to T lymphocytes, there is another important population of lymphocytes, the CD19+ receptor-bearing B lymphocytes. Comparing the numbers of T and B lymphocytes, it is clear that the amount of T lymphocytes is more than 6-fold. In contrast to T lymphocytes, this group of lymphocytes does not require any antigen presentation by macrophages or monocytes, since antigen recognition is performed by membrane-bound immunoglobulins. Furthermore, it is developmentally important to note that B lymphocytes can differentiate into plasma cells. As a crucial task of the B-lymphocytes is the production of antibodies.

Natural killer cells (NK cells).

  • Because NK cells have neither antigen specificity nor a detectable activation mechanism, these cells are considered part of the nonspecific cellular immune system. They are thought to function to destroy tumor cells and virus-infected cells.