Тяжелая цепная болезнь
| Тяжелая цепная болезнь | |
|---|---|
| Специальность | Иммунология , гематология |
Болезнь тяжелой цепи является формой парапротеинемии и дискразии плазматических клеток , которая включает пролиферацию клеток, продуцирующих тяжелые цепи иммуноглобулина . [ 1 ]
Это заболевание характеризуется чрезмерной продукцией тяжелых цепей, которые короткие и усеченные. Эти белки тяжелой цепи имеют различные делеции, в основном в их аминоконцевой части, что заставляет тяжелые цепи терять способность образовывать дисульфидные связи с легкими цепями . Дефект в иммуноглобулинах, по -видимому, возникает во время соматической гипермутации. [ 2 ] Удаление N-концевой части белка заболевания тяжелой цепи приводит к агрегации и передаче сигналов рецептора B-клеток , [ 3 ] предположительно из-за потери антиагрегационных свойств легкой цепи. [ 4 ]
Классификация
[ редактировать ]Есть четыре формы:
- Альфа -цепная болезнь [ 5 ] (Болезнь Селигмана)
- Болезнь гамма -цепи [ 6 ] [ 7 ] (Болезнь Франклина)
- MU Chain болезнь [ 8 ]
- delta chain disease[9]
IgA/αHCD
[edit]The most common type of heavy chain disease is the IgA type, known as αHCD. The most common type of αHCD is the gastrointestinal form (known as immunoproliferative small intestine disease or IPSID), but it has also been reported in the respiratory tract, and other areas of the body.[10]
IgG/γHCD
[edit]Franklin's disease (gamma heavy chain disease) It is a very rare B-cell lymphoplasma cell proliferative disorder which may be associated with autoimmune diseases and infection is a common characteristic of the disease.[6] It is characterized by lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly, and weakness. The most distinctive symptom is palatal edema, caused by nodal involvement of Waldeyer's ring. Diagnosis is made by the demonstration of an anomalous serum M component that reacts with anti-IgG but not anti-light chain reagents. Bone marrow examination is usually nondiagnostic. Patients usually have a rapid downhill course and die of infection if left untreated or misdiagnosed.
Patients with Franklin disease usually have a history of progressive weakness, fatigue, intermittent fever, night sweats and weight loss and may present with lymphadenopathy (62%), splenomegaly (52%) or hepatomegaly (37%). The fever is considered secondary to impaired cellular and humoral immunity, and thus recurrent infections are the common clinical presentation in Franklin disease. Weng et al. described the first case of Penicillium sp. infection in a patient with Franklin disease and emphasized the importance of proper preparation for biopsy, complete hematologic investigation, culture preparation and early antifungal coverage to improve the outcome.[6][10]
The γHCD can be divided into three categories based on the various clinical and pathological features. These categories are disseminated lymphoproliferative disease, localized proliferative disease and no apparent proliferative disease.
- Disseminated lymphoproliferative disease is found in 57–66% of patients diagnosed with γHCD. Lymphadenopathy and constitutional symptoms are the usual features.[11]
- Localized proliferative disease is found in approximately 25% of γHCD patients. This is characterized by a localization of the mutated heavy chains in extramedullary tissue, or solely in the bone marrow.[10]
- No apparent proliferative disease is seen in 9–17% of patients with γHCD, and there is almost always an underlying autoimmune disorder.[11]
IgM/μHCD
[edit]The IgM type of heavy chain disease, μHCD, is often misdiagnosed as chronic lymphoid leukemia (CLL) because the two diseases are often associated with each other and show similar symptoms.[11]
References
[edit]- ^ "Heavy Chain Diseases: Plasma Cell Disorders: Merck Manual Home Edition". Retrieved 2008-02-29.
- ^ Goossens T, Klein U, Küppers R (1998). "Frequent occurrence of deletions and duplications during somatic hypermutation: Implications for oncogene translocations and heavy chain disease". PNAS. 95 (5): 2463–8. Bibcode:1998PNAS...95.2463G. doi:10.1073/pnas.95.5.2463. PMC 19376. PMID 9482908.
- ^ Corcos D, Dunda O, Butor C, Cesbron JY, Lorès P, Bucchini D, Jami J (1995). "Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a heavy-chain disease protein". Curr. Biol. 5 (10): 1140–8. doi:10.1016/S0960-9822(95)00230-2. PMID 8548286. S2CID 18737035.
- ^ Corcos D, Osborn MJ, Matheson LS, Santos F, Zou X, Smith JA, Morgan G, Hutchings A, Hamon M, Oxley D, Brüggemann M (2010). "Immunoglobulin aggregation leading to Russell body formation is prevented by the antibody light chain". Blood. 115 (2): 282–8. doi:10.1182/blood-2009-07-234864. PMID 19822901.
- ^ Fakhfakh F, Dellagi K, Ayadi H, Bouguerra A, Fourati R, Ben Ayed F, Brouet JC, Tsapis A (1992). "Alpha heavy chain disease alpha mRNA contain nucleotide sequences of unknown origins". Eur. J. Immunol. 22 (11): 3037–40. doi:10.1002/eji.1830221141. PMID 1425927. S2CID 85132431.
- ^ Jump up to: a b c Weng CH, Wang RC, Hsieh TY, Tsai CA, Lin TH (July 2012). "Penicillium pneumonia in a patient with newly diagnosed Franklin disease". Am J Med Sci. 344 (1): 69–71. doi:10.1097/MAJ.0b013e31824a8927. PMID 22543591.
- ^ Wahner-Roedler DL, Witzig TE, Loehrer LL, Kyle RA (2003). "Gamma-heavy chain disease: review of 23 cases". Medicine (Baltimore). 82 (4): 236–50. doi:10.1097/01.md.0000085058.63483.7f. PMID 12861101. S2CID 5320931.
- ^ Wahner-Roedler DL, Kyle RA (1992). "Mu-heavy chain disease: presentation as a benign monoclonal gammopathy". Am. J. Hematol. 40 (1): 56–60. doi:10.1002/ajh.2830400112. PMID 1566748. S2CID 37749139.
- ^ Vilpo и, Irjala K, Viljanen MK, Klemi P, Kouvonen I, Rönnemaa T (1980). «Дельта-гивэвави болезнь цепи: исследование случая». Clin Immunol Immunopathol . 17 (4): 584-94. Doi : 10.1016/0090-1229 (80) 90154-3 . PMID 6777103 .
- ^ Jump up to: а беременный в Wahner-Roedler DL, Kyle RA (2005). «Желатели тяжелой цепи». Best Pract Res Clin Haematol . 18 (4): 729–46. doi : 10.1016/j.beha.2005.01.029 . PMID 16026747 .
- ^ Jump up to: а беременный в Fermand JP, Brouet JC, Danon F, Seligmann M (1989). «Болезнь гамма тяжелой цепи»: гетерогенность клинико -патологических особенностей. Отчет о 16 случаях и обзоре литературы » . Медицина (Балтимор) . 68 (6): 321–35. doi : 10.1097/00005792-198911000-00001 . PMID 2509855 . S2CID 29644848 .