When IgM syndrome is an immunoglobulin (Ig) deficiency, which is characterized by normal or elevated serum IgM levels and decreased or absent serum levels of other immunoglobulins, resulting in increased susceptibility to bacterial infections.
(See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.)
When IgM syndrome is an immunoglobulin (Ig) deficiency, which is characterized by normal or elevated serum IgM levels and decreased or absent serum levels of other immunoglobulins, resulting in increased susceptibility to bacterial infections. (See also Overview of immune deficiency disorders, and approach to the patient with an immunodeficiency disorder.) The Hyper-IgM syndrome is a primary immunodeficiency disease, which comprises the combined humoral and cellular immune deficiency disorders. It may be X-linked autosomal or. The manifestations vary depending on the mutation and its location. X-linked inherited Hyper-IgM syndrome Most cases are X-linked and are caused by mutations in a gene on the X chromosome that encodes a protein (CD154 or CD40 ligand) on the surface of activated T-helper cells encodes. In the presence of cytokines, the normal CD40 ligand interacts with B cells and signals them thereby to switch from production of IgM to the production of IgA, IgG or IgE. When an X-linked inherited Hyper-IgM syndrome lack the T cells a functional CD40 ligand, which is why they can not send such a signal to B cells. Consequently, the B-cells produce only IgM, the IgM levels may be normal or increased. In patients with this form of immune disease and severe neutropenia associated pneumonia occur in childhood with Pneumocystis jirovecii can. The lymphatic tissue is very small, since the signals of a defective CD40 ligand B cells do not activate. Otherwise, the clinical picture is similar to that of X-linked agammaglobulinemia inherited. During the first two years of life repeated pyogenic bacterial infections sinupulmonale occur. Susceptibility to Cryptosporidium infections may be increased. Many patients die before puberty and those who live longer, mostly suffering from cirrhosis or B-cell lymphoma. Autosomal recessive hyper-IgM syndrome When autosomal recessive hyper-IgM syndrome with a CD40 mutation similar to the manifestations of those of the X-linked form. At least 4 autosomal recessive forms a B-cell defect is present. Two of these forms (lack of activation-induced Zytidindesaminase [AID] or uracil-DNA glycosylase [UNG]) have much higher IgM levels than the X-linked form; in addition to a lymphoid hyperplasia (this includes lymphadenopathy, splenomegaly, and hypertrophy of the adenoids) may also autoimmune diseases exist. Leukopenia is not available. Diagnosis CD40 ligand expression and genetic testing The diagnosis of hyper-IgM syndrome is suspected based on clinical criteria. The Ig concentration in the serum are measured; normal and elevated IgM levels and low or absent levels of other immunoglobulins confirm the diagnosis. A testing of the CD40 ligand expression on the surfaces of T cells with flow cytometry should be performed. The diagnosis is, if possible, confirmed by genetic testing. Prenatal genetic testing women can be offered with trying to get pregnant if they have a family history of CD40 Ligandmangel. Genetic testing of other relatives is not performed routinely. Other laboratory findings include a reduced number of memory B cells (CD27) and the absence class changing memory B cells (IgD-CD27). Prophylactic therapy immunoglobulin (IgG) -Ersatztherapie and sometimes trimethoprim / sulfamethoxazole Hematopoietic bone marrow transplantation, the treatment of hyper-IgM syndrome usually involves eineImmunglobulin- replacement therapy. Patients with X-linked form of CD40 or mutations is administered trimethoprim / sulfamethoxazole for the prevention of P. jirovecii infection and environmental protection measures are taken to reduce the risk of Cryptosporidium infection (Overview of gastroenteritis: prevention) to reduce. Because of the poor prognosis, however, a hematopoietic stem cell transplant is preferred if an HLA-identical sibling donor is available as available.