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以下内容为X染色体相关无丙种球蛋白血症（X-linked agammaglobulinemia）的临时翻译：
| X染色体相关无丙种球蛋白血症 | |
|---|---|
| 分类和外部资源 | |
| ICD-10 | D80.0 |
| ICD-9-CM | 279.04 |
| OMIM | 300300 |
| DiseasesDB | 1728 |
| eMedicine | ped/294 derm/858 |
X染色体相关无丙种球蛋白血症（英文简称XLA，也称为伴性遗传低丙种球蛋白血症，X-连锁无丙种球蛋白血症，或者布鲁顿型无丙种球蛋白血症，伴性遗传无丙种球蛋白血症[1]:83，是一种罕见的X染色体基因缺陷疾病。该疾病与1952年被发现，其症状是影响人体对抗感染的机能。由于是X染色体上的缺陷，因此在男性中更为常见。存在这种缺陷的病人无法产生成熟的B细胞[2]，因此便先出来的具体症状是在血液中完全不存在抗体。作为免疫系统中一部分的B细胞，在正常的情况下应当产生抗体（又叫做免疫球蛋白），而抗体则是保持体液抗体免疫相应的重要一环。得此病的患者，若不经过治疗，可能会发展成严重感染，甚至可以致命。由于患者编码布氏酪氨酸激酶的基因发生了突变，这种酶通过激发B细胞受器（BCR）来调节B细胞的发育和成熟。由于突变导致B细胞的发育受到了严重的阻碍，并且降低了血清中抗体的产量。患此病的病人在年幼时期一般都会出现反复的感染，尤其是细胞外的被囊细菌感染[3]。该疾病的发生率为约1:100,000（男婴）[4]，并且没有没有种族遗传倾向。该疾病的治疗方法是注入人类抗体，使用汇集丙种免疫球蛋白并不能恢复具有正常功能的B细胞群落，但是可以通过外来抗体所带来的被动免疫减少和减轻感染情况[3]。
X染色体相关无丙种球蛋白血症是由于X染色体上的单个基因突变所引起的，这一于1993年被识别的基因，在正常情况下应当产生布氏酪氨酸激酶（简称Btk）[3]。这一疾病最初由奥格登·布鲁顿博士所描绘，在他1952年所发表的一篇突破性研究论文中，描述了一个无法对常见儿童疾病和感染产生免疫力的男孩[5]。这是人们所知道的第一个免疫缺陷，而现在它与所有基因遗传所致的免疫系统归类在一起，称为原发性免疫缺陷。
遗传学
所谓的Btk酶对于骨髓中B细胞的成熟扮演着至关重要的角色，当负责生产此酶的基因发生突变时，未成熟的前B淋巴细胞将无法转化为进入血液的成熟B细胞。这种失调症称为X联（是因为它和X染色体关联），并且会 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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诊断
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.
治疗
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.
其它注意事项
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.[来源请求]
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.
参见
参考文献
- ^ 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. 已忽略未知参数|month=（建议使用|date=） (帮助)
