G-CSF therapy may be useful for treatment of neutropenia.ġ1. IVIG replacement therapy is indicated for patients as well as PJP prophylaxis with trimethoprim-sulfamethoxazole. Sequencing of the gene for CD40L (TNFSF5) can confirm the diagnosis.ġ0. Rapid screening for X-linked Hyper IgM can be performed by flow cytometry to detect CD40L on activated T cells. T cell numbers and function are normal.ĩ. Patients lack switched memory B cells (CD27+IgM-IgD-) due to failed class-switch recombination. While the total numbers of B cells are normal, they have a naïve phenotype with expression of surface IgM and IgD. Specific antibody responses to vaccine antigens are decreased. It is important to note that one-half of patients actually have normal levels of IgM at initial presentation.
Classic laboratory findings include elevated IgM with very low serum IgG and IgA levels. Bone marrow analysis typically reveals a block in maturation at the pro-myelocyte to myelocyte stage.Ĩ. Neutropenic patients can develop oral ulcers and gingivitis. This can be chronic and exacerbated by acute infections. Intermittent neutropenia is observed in over 60% of patients.
#Hyper igm syndrome skin#
Other reported infections include bacterial sepsis, enterovirus CNS infections, and skin cellulitis/abscess.ħ. Cryptosporidium is also a major cause of sclerosing cholangitis in patients.Ħ. Chronic infectious diarrhea can occur from Cryptosporidium and Giardia. However, patients also develop opportunistic infections including Pneumocystis jiroveci pneumonia (which occurs in more than one-half of patients). Clinically patients present early in life with a phenotype consistent with antibody immunodeficiency: recurrent pneumonia, otitis media, and sinusitis with encapsulated bacteria. This defect in Th1 immunity may underlie the predisposition to opportunistic infections in these patientsĥ. The failure to secrete IL-12 impairs the ability of T cells to produce IFN-gamma and to activate monocytes. CD40L interaction with CD40 expressed on dendritic cells leads to secretion of IL-12 (a key cytokine in Th1 immunity). Patients with CD40 deficiency (HIGM Type 3) have an autosomal recessive form of hyper IgM syndrome which can present with features identical to X-linked hyper IgM syndrome.Ĥ. CD40L interacts with CD40 on the surface of B cells to activate immunoglobulin class-switching (shifting antibody production from IgM to IgG, IgA, or IgE) and to establish B cell memory.ģ. This disease is caused by mutations in CD40 ligand (CD40L), a molecule that is expressed on the surface of activated T cells. X-linked Hyper IgM syndrome (HIGM Type I) is a combined immune deficiency that is characterized by antibody deficiency as well as an impaired ability of T cells to activate monocytes and dendritic cells.Ģ.
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