This investigation immunodeficiency includes a medical history, physical examination and Untersuchnug of immune function with. The studies vary, based on the following criteria:

Immunodeficiency disorders associated with various complications, including infections, autoimmune diseases and lymphomas, and other cancers; Immunodeficiency disorders may also predispose to such complications affected patients. Primary immunodeficiency disorders are hereditary; secondary immunodeficiency disorders are acquired. Secondary immunodeficiency disorders are much more common. This investigation immunodeficiency includes a medical history, physical examination and Untersuchnug of immune function with. The studies vary, based on the following criteria: whether a primary or secondary immunodeficiency is suspected In primary immunodeficiency which component of the immune system appears to have a defect. Secondary immunodeficiencies Among the causes (see Table: causes of secondary immunodeficiency) include: Systemic diseases (. Eg diabetes, malnutrition, HIV infection) Immunosuppressive treatments (. Eg cytotoxic chemotherapy, bone marrow ablation prior to transplantation, radiotherapy) Longer heavy disease Secondary immunodeficiencies also occur in critically ill persons, the elderly or hospitalized patients. Longer, serious illnesses can weaken the immune response, in which the impairment is often reversible if the underlying illness subsides. Causes of secondary immunodeficiency category Examples endocrine system diabetes mellitus gastrointestinal hepatic failure, hepatitis, intestinal lymphangiectasia, protein-losing enteropathy Hämatologisch aplastic anemia, cancer (eg. As chronic lymphocytic leukemia, multiple myeloma, Hodgkin’s lymphoma), graft-versus-host disease , sickle cell anemia, splenectomy Iatrogenic Certain drugs, such as chemotherapeutic agents, immunosuppressive agents, corticosteroids; Radiotherapy; Splenectomy Infectious viral infections (eg. As cytomegalovirus, Epstein-Barr virus, HIV, measles virus, varicella-zoster virus), bacterial infections, bacterial infections with rare superantigens (antigens that activate large numbers of T cells can, resulting in a massive production of cytokines, particularly Staphylococcus aureus), mycobacterial infections, nutritional because alcoholism, malnutrition Physiologically Physiological immunodeficiency in children due to immaturity of the immune system, pregnancy Kidney nephrotic syndrome, renal failure, uremia Rheumatic SLE Other burns, cancer, chromosomal abnormalities (eg. B. Down syndrome), congenital asplenia, serious and chronic disease, histiocytosis, sarcoidosis Some medications that cause immunosuppression class examples anticonvulsant lamotrigine, phenytoin, valproate DMARDs (disease-modifying antirheumatic drugs) IL-1 inhibitors (eg. B. anakinra) IL-6 inhibitors (z. B. tocilizumab), IL-17 inhibitors (z. B. brodalumab) TNF inhibitors (z. B. adalimumab, etanercept, infliximab) T cell Ak tivierungs inhibitors (eg. B. Abatacept, basiliximab) CD20 inhibitors (z. B. Rituximab) CD3 inhibitors (z. B., muromonab-CD3) Janus kinase (JAK) inhibitors (eg. B. Ruxolitinib) calcineurin inhibitors cyclosporin, tacrolimus, corticosteroids methylprednisolone , prednisone Cytotoxic chemotherapeutic agents Several (see Table: antineoplastic drugs frequently used) inhibitors of purine metabolism azathioprine, mycophenolate mofetil (MMF) Rapamycins everolimus, sirolimus Immunosuppressive immunoglobulins anti-lymphocyte globulin, antithymocyte An immune deficiency by renal loss of serum protein (esp. IgG and albumin) arising from: The kidney in the nephrotic syndrome, the GI tract at enteropathy can also lead to a loss of lymphocytes and in consequence to lymphopenia The skin in severe burns or dermatitis. All these diseases can mimic B- and T-cell defects. The treatment focuses on the underlying disease; a diet with a high proportion of medium-chain triglycerides can reduce the loss of Imunglobulinen Igs) and lymphocytes from the gastrointestinal tract and prove to be extremely beneficial. When a suspected clinically relevant secondary immunodeficiency, the studies should focus on these (eg. As diabetes, HIV infection, cystic fibrosis, primary ciliary dyskinesia). Primary immunodeficiencies These diseases are genetically determined; they can occur as a single disease or as part of a syndrome. There have been described, which may among each other have a strong heterogeneity more than 100 of these disorders. With more than 80% of the molecular basis is known. The primary immune deficiencies manifest themselves usually in early childhood and childhood as abnormal frequent (recurrent) or unusual infections. At the first appearance of the disease about 70% of patients are <20 years old, and because of the often X-linked inheritance 60% of cases are male. The overall incidence of symptomatic immunodeficiencies is estimated at 1/280. The classification of the primary immunodeficiencies performed according to the main component of the immune system, which has a defect that is not present or defective: Humoral immunity Cellular immunity combined humoral and cellular immunity phagocytes complement proteins The more molecular defects are defined, the more likely is a classification based on molecular functional defects. Primary immunodeficiency syndromes are genetic immunodeficiencies with immunological and non-immunological manifestations. Not Immune Manifestations are often easier to recognize. Examples include ataxia-telangiectasia, cartilage-hair hypoplasia, DiGeorge syndrome, hyper IgE syndrome and Wiskott-Aldrich syndrome. Typically, immune deficiencies manifest as recurrent infections. The age, have begun in the recurrent infections, provides an indication of the affected components of the immune system. Further characteristic results suggest a preliminary clinical diagnosis close (see table: Characteristic clinical findings in some primary immunodeficiencies). However, there are laboratory tests to confirm the diagnosis required (see table: Original and additional laboratory tests immunodeficiency). Further tests are indicated if clinical findings or laboratory tests first suspect a specific disorder of immune cells or Komplementfunktionen suggest (see table: Specific and advanced laboratory tests for immunodeficiency *). The prognosis in primary immunodeficiency diseases depends on the specific disease. Humoral immune deficiency disorders humoral immune deficiency disorders (B-cell defects), which produce an antibody deficiency, make 50-60% of primary immunodeficiencies (see Table: humoral immunodeficiency disorders). By decreasing serum antibody titers, the susceptible bacterial infections increased. The most common B-cell defect is selective IgA deficiency For the diagnostic evaluation of humoral immunity defects, examination of patients with suspected immune deficiency and specific and advanced laboratory tests for immunodeficiency *. Humoral immunodeficiency disorders disease inheritance Affected genes Clinical findings common variable immunodeficiency Several TACI, ICOS, BAFFR Recurring sinopulmonary infections, autoimmune disorders (eg. As immune thrombocytopenia, autoimmune hemolytic anemia), malabsorption, giardiasis, granulomatous interstitial lung disease, nodular lymphoid hyperplasia of the stomach tract, bronchiectasis, lymphoid interstitial pneumonia, splenomegaly; 10% of gastric cancer and lymphoma Usually in patients aged 20-40 years Hereditary IgM proliferation diagnosed with AID or UNG defects Autosomal recessive AID, UNG Similar to X-linked inherited IgM increase, but with lymphatic hyperplasia No leukopenia Hyper IgM syndrome with CD40 deficiency Autosomal recessive CD40 Similar to X-linked inherited Hyper-IgM syndrome Lymphoid hypoplasia, neutropenia Hyper IgM syndrome with CD40 ligand deficiency X-linked CD40 ligand (CD40L) Similar to X-linked agammaglobulinemia inherited (z. B. recurrent pyogenic bacterial sinopulmonary infections), but greater incidence of Pneumocystis jirovecii infection, cryptosporidiosis, severe neutropenia and lymphoid hypoplasia Selective antibody deficiency with normal immunoglobulins Unknown - Recurrent sinopulmonary infections Sometimes atopic findings (eg atopic dermatitis, asthma, chronic rhinitis. ) can occur in mild, medium, heavy and memory phenotypes Selective IgA deficiency Unknown In some cases, TACI Mostly asymptomatic Recurring sinopulmonary infections Durchfal l, allergies (including anaphylactic reactions to transfusions [rare]), autoimmune diseases (e.g.. As celiac disease, inflammatory bowel disease, systemic lupus erythematosus, chronic active hepatitis) Transient hypogammaglobulinemia of childhood unknown - usually asymptomatic Sometimes recurrent sinopulmonary or gastrointestinal infection, candidiasis, meningitis X-linked agammaglobulinemia X-linked BTK Recurring sinopulmonary infections and skin infections during childhood, transient neutropenia, lymphoid hypoplasia persistent CNS infections resulting from liver-attenuated oral polio vaccine, echo viruses or Coxsackievirus Increased risk of infectious arthritis, bronchiectasis, and certain cancers AID = activation-dependent (induced) cytidine deaminase; BAFFR = B-cell activating factor receptor; BTK = Bruton's tyrosine kinase; C = Supplement; CAML = calcium-modulator and cyclophilin ligand; CD = cluster of differentiation; ICOS = Inducible T-cell co-stimulator; TACI = transmembrane activator and CAML interactor; UNG = uracil-DNA glycosylase. Cellular immune deficiency disorders cellular immune deficiency disorders (T-cell disorders) constitute about 5-10% of primary immunodeficiencies and make them vulnerable to infection by viruses, Pneumocystis jirovecii, fungi, other opportunistic organisms and many common pathogens (see table: cellular immunodeficiency disorders). Since the B and T cell immune system are interdependent, also T-cell defects can cause an immunoglobulin deficiency. The most common T-cell diseases are DiGeorge Syndrome ZAP-70 deficiency X-linked inherited lymphoproliferative syndrome Chronic mucocutaneous candidiasis Primary natural killer cell defects that occur very rarely do any work for viral infections and tumors prone. Primary natural killer cell defects can occur in patients who have various other primary or secondary immunodeficiency disorders. For the diagnostic investigation of cellular immunity deficit, see table: Original and additional laboratory tests to immunodeficiency and specific and advanced laboratory tests for immunodeficiency *. Cellular immune deficiency disorders disease inheritance Affected genes Clinical findings Chronic mucocutaneous candidiasis autosomal dominant or -rezessiv STAT1 (dominant) AIRE (recessive) Persistent or recurrent Candida infections, onychomycosis, autosomal recessive autoimmune disease polyendocrinopathy-candidiasis-ectodermal-Dystropie (with hypoparathyroidism and adrenal insufficiency) DiGeorge syndrome Autosomal Genes in the 22q11.2 chromosome 10p13 genes Unusual on facial expression with deep-seated ears, congenital heart disease (eg. B. abnormalities of the aortic arch), thymic hypoplasia or -aplasie, hypoparathyroidism with hypocalcemic tetany, recurrent infections, developmental delay X-linked inherited lymphoproliferative syndrome X-linked SH2D1A (type 1) XIAP (type 2) Asymptomatic to onset of Epstein-Barr virus infection then fulminant infectious mononucleosis or fatal liver failure, B-cell lymphoma, splenomegaly, aplastic anemia zeta-associated protein 70 (ZAP-70) deficiency Autosomal recessive - Frequent and opportunistic infections No CD8 cells AIRE = autoimmune regulator; CD = cluster of differentiation; SH2D1A = SH2 domain with 1A; STAT = signal transducer and activator of transcription; TYK = tyrosine; UNG = uracil DNA glycosylase; WASP = Wiskott-Aldrich syndrome protein; XIAP = X-linked inhibitor of apoptosis. Combined humoral and cellular immune deficiency disorders Approximately 20% of primary immunodeficiencies are combined humoral and cellular immune deficiency disorders (B- and T-cell defects) (see Table: combined humoral and cellular immune deficiency disorders). The main form is Severe combined immunodeficiency (SCID) In ??some forms of the combined immunodeficiency syndrome (z. B. purine nucleoside phosphorylase deficiency) immunoglobulin levels are normal or elevated, due to the inadequate T-cell function, however, is the formation of antibodies impaired. for diagnostic Untersuchnug of combined humoral and cellular immune deficiency disorders, see table: Specific and advanced laboratory tests for immunodeficiency *. Combined humoral and cellular immune deficiency disorders disease inheritance Affected genes Clinical findings ataxia telangiectasia Autosomal recessive ATM ataxia telangiectasia, recurrent sinopulmonary infections, endocrine disorders (eg. As impaired gonadal development, testicular atrophy, diabetes mellitus), increased risk of cancer cartilage-hair hypoplasia autosomal recessive - Short link Riger short stature, frequent and opportunistic infections Combined Immunodeficiency with insufficient but existing T-cell function and normal or elevated immunoglobulin autosomal recessive or X-linked NEMO Frequent and opportunistic infections, lymphopenia, lymphadenopathy, hepatosplenomegaly, skin lesions in some patients similar to those of Langerhans cell histiocytosis hyper IgE syndrome Autosomal dominant or -rezessiv STAT3 (dominant) TYK2, DOCK8 (recessive) sinopulmonary infections; Staphylococcal abscesses of the skin, lungs, joints and internal organs; pulmonary pneumatoceles; itchy dermatitis; coarse facial features; Delayed loss of deciduous teeth; osteopenia; recurrent fractures; Eosinophilia in tissue and blood MHC antigen deficient Autosomal recessive - Frequent and opportunistic infections severe combined immunodeficiency autosomal recessive, or X-linked JAK3, PTPRC (CD45]) RAG1, RAG2 (autosomal recessive) IL-2RG (X-linked ) Oral candidiasis, P. jirovecii pneumonia, diarrhea within six months, failure to thrive, graft-versus-host disease, lack of Thymusschatten, lymphopenia, bone abnormalities (ADA deficiency), exfoliative dermatitis as part of Ommen's syndrome Wiskott-Aldrich Syndrome X-linked recessive WASP Typically pyogenic and opportunistic infections, eczema, thrombocytopenia may gastrointestinal bleeding (eg. B. bloody diarrhea), recurrent respiratory infections, cancer (in 10% of patients> 10 years), varicella zoster virus infection, herpes virus infection ADA = adenosine deaminase; ATM = ataxia telangiectasia-mutated; DOCK = Dedicator of cytokinesis; IL-2RG = IL-2 receptor gamma; ITGB2 = integrin beta-2; JAK = Janus kinase; MHC = major histocompatibility complex; NEMO = Nucklearer factor-kappa B essential modulator; PTPRC = protein tyrosine phosphatase, receptor type, C; RAG = eekombinationsaktivierendes gene; STAT = signal transducer and activator of transcription; TYK = tyrosine; WASP = Wiskott-Aldrich syndrome protein. Phagocytic cell defects Phagozytendefekte provide 10-15% of primary immunodeficiencies; the ability of phagocytes (. e.g., monocytes, macrophages, neutrophils, and eosinophils), to destroy pathogens is impaired (see Table: Phagocytic cell defects). Also characteristic skin infections with staphylococcus and Gram-negative pathogens. The most common (although still rare) phagocytic cell defects Chronic granulomatosis Leukocyte adhesion deficiency (types 1 and 2) Cyclical neutropenia Chediak-Higashi syndrome For the diagnostic evaluation of phagocytic cell defects, see table: Original and additional laboratory tests to immunodeficiency and specific and advanced laboratory tests in immunodeficient *. Phagocytic cell defects disease inheritance Affected genes Clinical findings Chediak-Higashi syndrome Autosomal recessive LYST (CHS1) Oculocutaneous albinism, susceptibility to infections, fever, jaundice, hepatosplenomegaly, lymphadenopathy, neuropathy, pancytopenia, bleeding Chronic granulomatous disease X-linked or autosomal recessive gp91Ppfox (CYBB ; X-linked) p22phox, p47phox, p67phox (autosomal -rezessiv) Granulomatous lesions in the lungs, liver, lymph nodes and in the gastrointestinal and genitourinary tract (causing obstruction); Lymphadenitis, hepatosplenomegaly, skin, gramnegative- lymph nodes, lung, liver, and perianal abscess, osteomyelitis, pneumonia, staphylococcus and aspergillus infections Leukocyte adhesion Autosomal recessive ITGB2 gene encodes CD18 of beta 2-integrins (type 1) GDP-fucose transporter gene (type 2) soft tissue infections, periodontal disease, poor wound healing, delayed umbilical cord separation, leukocytosis, no pus formation retardation (type 2) Mendel susceptibility to mycobacterial disease (MSMD) Autosomal dominant or -rezessiv defects in genes encoding the IFN-gamma- receptor, IL-12 or IL-12-Rez eptor encode Mycobacterial infections Different clinical severity based on genetic defect Cyclical neutropenia Autosomal dominant ELA2 Pyogenic bacterial infections during recurrent episodes of neutropenia (eg. B. every 14 to 35 days) CD = cluster of differentiation; CHS = Chediak-Higashi syndrome; CYBB cytochrome b =-245, beta polypeptide; DOCK = “Dedicator” of cytokinesis; ELA = elastase; GDP = glucose diphosphate; gp = glycoprotein; IFN = interferon; ITGB2 = integrin beta-2; JAK = Janus kinase; LYST = lysosomal transporter; , Defects of the complement system Komplementdefekte are rare (? 2%); is single (hereditary or acquired) Defects of complement components or inhibitors (see Table: defects of the complement system). With the exception of autosomal dominant C1 inhibitor deficiency and X-linked inherited defect properdin hereditary defects are inherited in an autosomal recessive manner. The Komplementdefekte result in inadequate opsonization, phagocytosis and lysis of pathogens and to poor resolution of antigen-antibody complexes. The most severe consequences are recurrent infection due to defective opsonization autoimmune diseases (z. B. SLE [Saint Louis encephalitis], glomerulonephritis) as a result of inadequate resolution of antigen-antibody complexes. A lack of a komplementregulatorischen protein causes hereditary angioedema. Komplementdefekte to the classical pathway and / or the alternative pathway concern (complement). The alternative path splits C3 and C5 through C9 with the classic way, but has additional components: factor D factor B, properdin (P) and regulatory factors H and I. For the diagnostic evaluation of Komplementdefekte, see table: Original and additional laboratory tests to immunodeficiency and specific and advanced laboratory tests for immunodeficiency *. Defects in the complement system disease inheritance Clinical findings C1 Autosomal recessive SLE C2 Autosomal recessive systemic lupus erythematosus, recurrent purulent infections with encapsulated bacteria (mainly pneumococcal) that begin in early childhood, other autoimmune diseases (eg. Glomerulonephritis, polymyositis, vasculitis, Henoch-Schonlein purpura, Hodgkin’s lymphoma) C3 Autosomal-rezessiv Wiederkehrende eitrige Infektionen mit verkapselten Bakterien, die bereits bei der Geburt beginnen, Glomerulonephritis, andere Antigen-Antikörper-Komplex-Erkrankungen, Sepsis C4 Autosomal-rezessiv Systemischer Lupus erythematodes, andere Autoimmunerkrankungen (z. B. IgA-Nephropathie, progressive systemische Sklerose, Purpura Schönlein-Henoch, Typ-1-Diabetes mellitus, Autoimmun-Hepatitis) C5, C6, C7, C8, C9 (Membranangriffskomplex) Autosomal-rezessiv Wiederkehrende Neisseria meningitidis und verbreitet N. gonorrhoeaeinfektionen Komplementdefekte bei der MBL-Aktivierung MBL Autosomal-rezessiv Wiederkehrende eitrige Infektionen mit verkapselten Bakterien, die bei der Geburt beginnen; unerklärliche Sepsis; erhöhte Schwere der Infektion bei sekundären Immundefekten durch die Anwendung von Kortikosteroiden; zystische Fibrose oder chronische Lungenerkrankungen

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