What is CD40 ligand deficiency?

What is CD40 ligand deficiency?

CD40 ligand (CD40L) deficiency or X-linked Hyper-IgM syndrome is a severe primary immunodeficiency caused by mutations in the CD40L gene. Despite currently available treatments, CD40L-deficient patients remain susceptible to life-threatening infections and have poor long term survival.

What causes hyper IgM syndrome?

Hyper IgM syndromes are caused by very rare, one-in-a-million, and potentially life-threatening genetic mutations that severely compromise the immune system and resulting in the individual’s inability to produce antibodies. Patients with hyper IgM are at significant risk for opportunistic and repeated infections.

How common is CD40 ligand deficiency?

CD40 ligand deficiency is an uncommon primary immune deficiency with an estimated annual incidence of 1 in 106 (1).

What does immunodeficiency with elevated IgM result in?

Immunodeficiency with hyper-IgM (HIM) is a rare primary immunodeficiency characterized by the production of normal to increased amounts of IgM antibody of questionable quality and an inability to produce sufficient quantities of IgG and IgA.

Where is CD40 expressed?

CD40 is constitutively expressed by antigen presenting cells, including dendritic cells, B cells and macrophages. It can also be expressed by endothelial cells, smooth muscle cells, fibroblasts and epithelial cells.

When does Hyper IgM present?

Diagnosis of Hyper IgM Syndromes XHIGM should be considered in any boy presenting with severe recurrent respiratory infections or an opportunistic infection who has low or absent IgG and normal or elevated IgM levels. Failure to express CD40 ligand on activated T-cells is a characteristic finding.

Is IgA deficiency an autoimmune disease?

A deficiency seems to play a part in asthma and allergies. Researchers have also linked IgA deficiency to autoimmune health problems. These are health problems that cause your body’s immune system to attack your body by mistake.

What is the prognosis of CD40 ligand deficiency?

CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative.

What is CD40 immunology?

Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

What does the CD40 ligand do?

CD40L mediates a range of activities on B cells, including induction of activation-associated surface antigen, entry into cell cycle, isotype switching, Ig secretion, and memory generation. CD40–CD40L interaction also plays important roles in monocyte activation and DC maturation.

How is CD40 ligand deficiency related to CSR?

CD40-ligand deficiency is the most common CSR-D and accounts for around 50% of all such patients (Figure 15.2). It is caused by harmful mutations in the CD40L gene, which is located on the X chromosome. Interaction between CD40L expressed by the T FH subset and its receptor CD40 on B cells induces B cell proliferation, CSR, and SHM (see above).

What is the role of CD40 ligand in lymphocytes?

CD40 ligand (CD40L) is involved in the differentiation of naïve T-lymphocytes into TH 1 effector cells. 207 In humans, deficiency of CD40L causes X-liked hyper IgM (XHIM) syndrome.

What kind of immunoglobulin defect does CD40L cause?

Defects in CD40L are the cause of an X-linked immunodeficiency with hyperlgM (HIGM1), an immunoglobulin switch defect characterized by elevated concentrations of IgM and decreased amounts of all other isotypes 9, 10. CD40L knockout mice fail to mount secondary antibody responses to T cell-dependent antigens and undergo isotype class switching 11.

How does CD40L deficiency affect male and female?

CD40L deficiency affects males because it is an inherited in XR trait. Female carriers, even with extreme lyonization, have been immunocompetent and without clinical illness. Females with hypogammaglobulinemia and high IgM levels should be tested for gene mutations that affect other forms of HIGM.