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X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia, XLA, Bruton type agammaglobulinemia, Bruton syndrome, or Sex-linked agammaglobulinemia) is a rare X-linked genetic disorder discovered in 1952 that affects the body's ability to fight infection. XLA is an X-linked disorder, and therefore is much more common in males. XLA patients do not generate mature B cells,〔(【引用サイトリンク】title=X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional )〕 which manifests as a complete lack of antibodies in their bloodstream. B cells are part of the immune system and normally manufacture antibodies (called immunoglobulins), which defend the body from infections by sustaining an immunological humoral antibody response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development (at the pro-B to pre-B cell stage) and a reduced Immunoglobulin (antibody) production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria.〔 It occurs in a frequency of about 1 in 100,000 male newborns, and has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.〔(X-Linked Agammaglobulinemia ) Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation〕 XLA is caused by a mutation on the X chromosome of a single gene identified in 1993 which produces an enzyme known as Bruton's tyrosine kinase, or Btk.〔 XLA was first characterized by Dr. Ogden Bruton in a ground-breaking research paper published in 1952 describing a boy unable to develop immunities to common childhood diseases and infections.〔. Reproduced in 〕 It is the first known immune deficiency, and is classified with other inherited (genetic) defects of the immune system, known as primary immunodeficiency disorders. ==Genetics== The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pro-B lymphocytes are unable to develop into pre-B lymphocytes, which normally develop into mature (naive) B cells that leave the bone marrow into the blood stream. The disorder is inherited in an X-linked recessive fashion as the gene linked to it is on the X chromosome) and is almost entirely limited to the sons of asymptomatic female carriers.〔 This is because males have only one copy of the X chromosome, while females have two copies; one normal copy of an X chromosome can compensate for mutations in the other X chromosome, so they are less likely to be symptomatic. If a carrier female gives birth to a male child, there is a 50% chance that the male will have XLA. A carrier female has a 25% chance overall of giving birth to an affected male child. An XLA patient will pass on the gene, and all of his daughters will be XLA carriers, meaning that any male grandchildren from an XLA patient's daughters have a 50% chance of inheriting XLA. A female XLA patient can arise only as the child of an XLA patient and a carrier mother. XLA can also rarely result from a spontaneous mutation in the fetus of a non-carrier mother. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「X-linked agammaglobulinemia」の詳細全文を読む スポンサード リンク
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