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以下內容為X染色體相關無丙種球蛋白血症（X-linked agammaglobulinemia）的臨時翻譯：
| X染色體相關無丙種球蛋白血症 | |
|---|---|
| 分類和外部資源 | |
| ICD-10 | D80.0 |
| ICD-9-CM | 279.04 |
| OMIM | 300300 |
| DiseasesDB | 1728 |
| eMedicine | ped/294 derm/858 |
X染色體相關無丙種球蛋白血症（英文簡稱XLA，也稱為伴性遺傳低丙種球蛋白血症，X-連鎖無丙種球蛋白血症，或者布魯頓型無丙種球蛋白血症，伴性遺傳無丙種球蛋白血症[1]:83，是一種罕見的X染色體基因缺陷疾病。該疾病與1952年被發現，其症狀是影響人體對抗感染的機能。由於是X染色體上的缺陷，因此在男性中更為常見。存在這種缺陷的病人無法產生成熟的B細胞[2]，因此便先出來的具體症狀是在血液中完全不存在抗體。作為免疫系統中一部分的B細胞，在正常的情況下應當產生抗體（又叫做免疫球蛋白），而抗體則是保持體液抗體免疫相應的重要一環。得此病的患者，若不經過治療，可能會發展成嚴重感染，甚至可以致命。由於患者編碼布氏酪氨酸激酶的基因發生了突變，這種酶通過激發B細胞受器（BCR）來調節B細胞的發育和成熟。由於突變導致B細胞的發育受到了嚴重的阻礙，並且降低了血清中抗體的產量。患此病的病人在年幼時期一般都會出現反覆的感染，尤其是細胞外的被囊細菌感染[3]。該疾病的發生率為約1:100,000（男嬰）[4]，並且沒有沒有種族遺傳傾向。該疾病的治療方法是注入人類抗體，使用匯集丙種免疫球蛋白並不能恢復具有正常功能的B細胞群落，但是可以通過外來抗體所帶來的被動免疫減少和減輕感染情況[3]。
X染色體相關無丙種球蛋白血症是由於X染色體上的單個基因突變所引起的，這一於1993年被識別的基因，在正常情況下應當產生布氏酪氨酸激酶（簡稱Btk）[3]。這一疾病最初由奧格登·布魯頓博士所描繪，在他1952年所發表的一篇突破性研究論文中，描述了一個無法對常見兒童疾病和感染產生免疫力的男孩[5]。這是人們所知道的第一個免疫缺陷，而現在它與所有基因遺傳所致的免疫系統歸類在一起，稱為原發性免疫缺陷。
遺傳學
所謂的Btk酶對於骨髓中B細胞的成熟扮演着至關重要的角色，當負責生產此酶的基因發生突變時，未成熟的前B淋巴細胞將無法轉化為進入血液的成熟B細胞。這種失調症稱為X聯（是因為它和X染色體關聯），並且會 The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pre-B lymphocytes are unable to develop into mature B cells that leave the bone marrow into the blood stream. The disorder is X-linked (it is on the X chromosome), and is almost entirely limited to the sons of asymptomatic female carriers [3]. 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. Females carriers have a 50% chance of giving birth to a male child with XLA.
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.
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診斷
XLA diagnosis usually begins due to a history of recurrent infections, mostly in the respiratory tract, through childhood. The diagnosis is probable when blood tests show the complete lack of circulating B cells (determined by the B cell marker CD19 and/or CD20), as well as low levels of all antibody classes, including IgG, IgA, IgM, IgE and IgD.[3]
When XLA is suspected, it is possible to do a Western Blot test to determine whether the Btk protein is being expressed. Results of a genetic blood test confirm the diagnosis and will identify the specific Btk mutation,[3] however its cost prohibits its use in routine screening for all pregnancies. Women with an XLA patient in their family should seek genetic counseling before pregnancy.
Although the symptoms of a XLA and other primary immune diseases (PID) include repeated and often severe infections, the average time for a diagnosis of a PID can be up to 10 years.
治療
The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every 3–4 weeks, for life. IVIg is a human product extracted and pooled from thousands of blood donations. IVIg does not cure XLA but increases the patient's lifespan and quality of life, by generating passive immunity, and boosting the immune system.[3] With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may live a relatively healthy life. A patient should attempt reaching a state where his IgG blood count exceeds 800 mg/kg. The dose is based on the patient's weight and IgG blood-count.
Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful; hence, IMIg is now uncommon.
Subcutaneous treatment (SCIg) was recently approved by the U.S. Food and Drug Administration (FDA), which is recommended in cases of severe adverse reactions to the IVIg treatment.
Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long-term treatment, if possible.
One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long-term success and complications of this treatment are, as yet, unknown.
其它注意事項
Serology (detection on antibodies to a specific pathogen or antigen) is often used to diagnose viral diseases. Because XLA patients lack antibodies, these tests always give a negative result regardless of their real condition. This applies to standard HIV tests. Special blood tests (such as the western blot based test) are required for proper viral diagnosis in XLA patients.[來源請求]
It is not recommended and dangerous for XLA patients to receive live attenuated vaccines such as live polio, or the measles, mumps, rubella (MMR vaccine).[3] Special emphasis is given to avoiding the oral live attenuated SABIN-type polio vaccine that has been reported to cause polio to XLA patients. Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.
XLA patients are specifically susceptible to viruses of the Enterovirus family, and mostly to: polio virus, coxsackie virus (hand, foot, and mouth disease) and Echoviruses. These may cause severe central nervous system conditions as chronic encephalitis, meningitis and death. An experimental anti-viral agent, pleconaril, is active against picornaviruses. XLA patients, however, are apparently immune to the Epstein-Barr virus (EBV), as they lack mature B cells (and so HLA co-receptors) needed for the viral infection.[6]
It is not known if XLA patients are able to generate an allergic reaction, as they lack functional IgE antibodies.
There is no special hazard for XLA patients in dealing with pets or outdoor activities.[3]
Unlike in other primary immunodeficiencies XLA patients are at no greater risk for developing autoimmune illnesses.
Agammaglobulinemia (XLA) is similar to the primary immunodeficiency disorder Hypogammaglobulinemia (CVID), and their clinical conditions and treatment are almost identical. However, while XLA is a congenital disorder, with known genetic causes, CVID may occur in adulthood and its causes are not yet understood. XLA was also historically mistaken as Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble boys").
A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a similar, yet milder, immune deficiency as in XLA.
參見
參考文獻
- ^ James, William D.; Berger, Timothy G.; et al. Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. 2006. ISBN 0-7216-2921-0.
- ^ X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional. [2008-03-01].
- ^ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation
- ^ Mahmoudi, Massoud. Allergy and Asthma: Practical Diagnosis and Management. McGraw-Hill Professional. 2007. ISBN 978-0-07-147173-2.
- ^ Bruton OC. Agammaglobulinemia. Pediatrics. 1952, 9 (6): 722–8. PMID 14929630.. Reproduced in Buckley CR. Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9:722-728. Pediatrics. 1998, 102 (1 Pt 2): 213–5. PMID 9651432.
- ^ Faulkner GC, Burrows SR, Khanna R, Moss DJ, Bird AG, Crawford DH. X-Linked agammaglobulinemia patients are not infected with Epstein-Barr virus: implications for the biology of the virus. Journal of Virology. 1999, 73 (2): 1555–64. PMC 103980
. PMID 9882361. 已忽略未知參數|month=（建議使用|date=） (幫助)
