Primary immunodeficiencies are classified and published several years ago by a scientific working group of the World Health Organization (WHO). Immunological and molecular genetic advances allow the classification of immune deficiencies in the B and T lymphocyte system (selective or combined), complement defects or immunodeficiencies as partial symptoms of other genetic diseases. Because of the high risk of infection, genetically determined changes in the hematopoietic system such as congenital neutropenia are also counted as PID. The WHO distinguishes eight subgroups of primary immunodeficiencies:
Combined immune deficiencies of the B and T lymphocyte system
Immunodeficiencies in which an antibody deficiency is superficial
Immunodeficiencies in which a T-lymphocyte defect is in the foreground
Other well-defined immunodeficiency syndromes
Immunodeficiencies with lymphoproliferative disease
Immunodeficiencies associated with or consequence of another disease
Complementary defects
Defects of granulocytes and macrophages.
Combined immune deficiencies of the B and T lymphocyte system
In combined immunodeficiencies, both B and T lymphocytes are affected. The most severe form of the illness is the combined immunodeficiency (severe combined immunodeficiency, SCID) with quantitative and/or functional impairment of T and B lymphocytes. Combined immune deficiencies usually manifest as early as infancy. Conspicuous accumulated opportunistic infections such as cytomegalovirus or Pneumocystis jiroveci (formerly carinii), as well as lymphadenopathies, chronic diarrhea, failure to thrive as well as inflammatory changes of the skin and mucous membranes are typical. Without therapy, most infants will die within the first year of life. The potentially curative form of therapy is stem cell transplantation. In individual cases, somatic gene therapy is also possible. Examples of combined immunodeficiencies include SCID (T-B +), SCID (TB), Omenn syndrome, X-linked hyper IgM syndrome, CD40 deficiency, CD8 deficiency, ZAP-70 defect or TAP-1 and TAP-2 defect.
Immunodeficiencies in which an antibody deficiency is superficial
Immunodeficiencies, with superficial antibody deficiency, show either disturbed B-cell differentiation or lacking or defective T-cell-dependent stimulation of B lymphocytes. Due to the maternal IgG antibodies (nest protection) transmitted diaplacentally, these defects do not manifest until early infancy. Some are recognized only in adolescence or even adulthood. Striking are infections with pyogenic pathogens such as streptococci and staphylococci. Examples of immunodeficiencies that focus on an antibody deficiency are X-linked agammaglobulinemia (XLA), immunoglobulin heavy chain defect, selective deficiency of certain immunoglobulin isotypes such as IgA deficiency or IgG subclass defect, k-chain defect, activation-induced Cytidine deaminase defect (AID deficiency) or transitory hypogammaglobulinemia of infants.
Immunodeficiencies in which a T-lymphocyte defect in the foreground
In addition to the diseases already listed, there are defects that mainly affect T lymphocytes. Genetics and pathogenesis of this group of diseases have not been sufficiently explored. The symptoms are the same as in the combined immunodeficiencies. Examples of immunodeficiencies in which a T lymphocyte defect is in the foreground are idiopathic CD4 lymphopenia, interleukin 2 deficiency, multiple cytokine deficiency or defects in intracellular lymphocytic signal transduction.
Other well-defined immunodeficiency syndromes
There are immune deficiencies that affect other organ systems, such as the cerebellum in Louis-Bar syndrome or the heart in DiGeorge syndrome. The immune defect is in the foreground and is mainly responsible for the symptoms. Depending on the disease pattern, conspicuous features include thrombocytopenia, anemia, infections, autoimmune changes, ataxia, lymphomas and an increased sensitivity to ionizing radiation. Examples of the group "other well-defined immunodeficiency syndromes" are Louis Bar Syndrome, DiGeorge syndrome, Wiskott-Aldrich syndrome, Nijmegen breakage syndrome, familial hemophagocytic lymphohistiocytosis (FHL) or X-linked lymphoproliferative syndromes such as the Purtilo Syndrome and Duncan syndrome.
Immunodeficiencies with a lymphoproliferative disease
Immunodeficiencies with the lymphoproliferative disease are based on a disturbed apoptosis induction. Clinical symptoms are mainly swollen lymph nodes, hepato- and/or splenomegaly, hemolytic anemia, autoimmune thrombocytopenia, neutropenia and polyclonal hypergammaglobulinemia. The main representative of this group is the autoimmune lymphoproliferative syndrome (ALPS).
Immunodeficiencies associated with or consequence of another disease: defects of granulocytes and macrophages
Defects of the granulocytes and macrophages may be caused by the differentiation, motility and intracellular formation of oxygen radicals. They often manifest in the form of abscessing bacterial infections and/or fungal infections. Examples of this group are Kostmann syndrome, Shwachman-Bodian-Diamond syndrome, cyclic or X-chromosomal neutropenia and type 1 and 2 leukocyte adhesion defects.