cold agglutinin disease

寒冷凝集素症

WordNet

1. unconscious from a blow or shock or intoxication; "the boxer was out cold"; "pass out cold"
2. a mild viral infection involving the nose and respiratory passages (but not the lungs); "will they never find a cure for the common cold?" (同)common_cold
3. the sensation produced by low temperatures; "he shivered from the cold"; "the cold helped clear his head" (同)coldness
4. without compunction or human feeling; "in cold blood"; "cold-blooded killing"; "insensate destruction" (同)cold-blooded, inhuman, insensate
5. sexually unresponsive; "was cold to his advances"; "a frigid woman" (同)frigid
6. lacking originality or spontaneity; no longer new; "moth-eaten theories about race"; "stale news" (同)stale, dusty, moth-eaten
7. (color) giving no sensation of warmth; "a cold bluish grey"
8. extended meanings; especially of psychological coldness; without human warmth or emotion; "a cold unfriendly nod"; "a cold and unaffectionate person"; "a cold impersonal manner"; "cold logic"; "the concert left me cold"
9. feeling or showing no enthusiasm; "a cold audience"; "a cold response to the new play"
10. having a low or inadequate temperature or feeling a sensation of coldness or having been made cold by e.g. ice or refrigeration; "a cold climate"; "a cold room"; "dinner has gotten cold"; "cold fingers"; "if you are cold, turn up the heat"; "a cold beer"
11. having lost freshness through passage of time; "a cold trail"; "dogs attempting to catch a cold scent"
12. lacking the warmth of life; "cold in his grave"
13. marked by errorless familiarity; "had her lines cold before rehearsals started"
14. of a seeker; far from the object sought
15. so intense as to be almost uncontrollable; "cold fury gripped him"
16. an impairment of health or a condition of abnormal functioning
17. caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological
18. an antibody that causes agglutination of a specific antigen
19. a pass between mountain peaks (同)gap

PrepTutorEJDIC

1. 『寒い』,冷たい;冷えた,冷やした / (性格・態度などが)『冷たい』,冷淡な,熱意のない;無情な,冷酷な / (物事が)人をがっかりさせる,つまらない / (色調が)冷たい,寒色の / (獲物のにおい臭が)かすかな,弱い / 《話》(打撃などで)意識を失った,失神した / 完全に,全く / 〈U〉《しばしばthe~》『寒さ』,寒け,冷たさ / 〈C〉,時に〈U〉『かぜ』,感冒
2. (体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
3. 女性の話術芸人 =diseur
4. 病気にかかった / 病的な,不健全な(morbid)
5. 凝集素(赤血球などの凝集反応を起こす抗体)
6. (山脈の)鞍部(あんぶ),山あい

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/27 20:30:42」(JST)

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[Wiki en表示]

Cold agglutinin disease
Classification and external resources
Cold agglutination - at body temperature, the antibodies do not attach to the red blood cells. At lower temperatures, however, the antibodies react to Ii antigens, bringing the red blood cells together, a process known as agglutination
ICD-10	D59.1
ICD-9	283.0
DiseasesDB	2949
eMedicine	med/408
MeSH	D000744

Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies only bind red blood cells at low body temperatures, typically 28-31°C.

It was first described in 1957.

Etiology

There are two forms of cold agglutinin disease: 1-primary and 2-secondary.

• The primary form is by definition idiopathic, a disease for which no cause is known.

• Secondary cold agglutinin disease is a result of an underlying condition.
  • In adults, this is typically due to a lymphoproliferative disease such as lymphoma and chronic lymphoid leukemia, or infection.
  • In children, cold agglutinin disease is often secondary to an infection, such as Mycoplasma pneumonia, mononucleosis, and HIV.

Pathophysiology

All individuals have circulating antibodies directed against red blood cells, but their concentrations are often too low to trigger disease (titers under 64 at 4°C). In individuals with cold agglutinin disease, these antibodies are in much higher concentrations (titers over 1000 at 4°C).

At body temperatures of 28-31°C, such as those encountered during winter months, and occasionally at body temperatures of 37°C, antibodies (generally IgM) bind to the polysaccharide region of glycoproteins on the surface of red blood cells (typically the I antigen, i antigen, and Pr antigens). Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response is sufficient, red blood cells are damaged by the membrane attack complex, an effector of the complement cascade. In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, forming pores that lead to membrane instability and intravascular hemolysis (destruction of the red blood cell within the blood vessels).

If the complement response is insufficient to form membrane attack complexes, then extravascular lysis will be favored over intravascular red blood cell lysis. In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This opsonization enhances the clearance of red blood cell by phagocytes in the liver, spleen, and lungs, a process termed extravascular hemolysis.

Individuals with cold agglutinin disease present with signs and symptoms of hemolytic anemia. Those with secondary agglutinin disease may also present with an underlying disease, often autoimmune.

Treatment

• Avoid cold weather.
• Treat the underlying lymphoma.

Treatment with rituximab has been described.

See also

• Warm antibody autoimmune hemolytic anemia
• List of hematologic conditions

References

UpToDate Contents

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• 1. 自己免疫性溶血性貧血の臨床的特徴および治療：寒冷凝集素 clinical features and treatment of autoimmune hemolytic anemia cold agglutinins
• 2. 自己免疫性溶血性貧血の病因：寒冷凝集素症 pathogenesis of autoimmune hemolytic anemia cold agglutinin disease
• 3. 小児における溶血性貧血の概要 overview of hemolytic anemias in children
• 4. 成人における肺炎マイコプラズマ感染症 mycoplasma pneumoniae infection in adults
• 5. 小児におけるマイコプラズマ肺炎感染 mycoplasma pneumoniae infection in children

English Journal

• Successful treatment with rituximab and mycophenolate mofetil of refractory autoimmune hemolytic anemia post-hematopoietic stem cell transplant for dyskeratosis congenita due to TINF2 mutation.

• O'Connell N, Goodyer M, Gleeson M, Storey L, Williams M, Cotter M, O'Marcaigh A, Smith O.Author information Department of Haematology, Our Lady's Children's Hospital, Dublin, Ireland.AbstractAIHA following allogeneic HSCT is appearing more frequently in the literature. It occurs as a result of donor cell-derived antibodies targeting donor red cell antigens. Little guidance exists on the management of such patients, particularly in the pediatric setting. First-line conventional treatment is corticosteroids and/or immunoglobulin therapy with monoclonal antibody therapy reserved for treatment failure. We report our experience of a child refractory to immunoglobulin and steroid therapy who required several infusions of rituximab and immunomodulatory therapy to obtain a clinically significant response.
• Pediatric transplantation.Pediatr Transplant.2014 Feb;18(1):E22-4. doi: 10.1111/petr.12172. Epub 2013 Oct 29.
• AIHA following allogeneic HSCT is appearing more frequently in the literature. It occurs as a result of donor cell-derived antibodies targeting donor red cell antigens. Little guidance exists on the management of such patients, particularly in the pediatric setting. First-line conventional treatment
• PMID 24168326

• Lack of Galactosylation Enhances the Pathogenic Activity of IgG1 but Not IgG2a Anti-Erythrocyte Autoantibodies.

• Ito K, Furukawa J, Yamada K, Tran NL, Shinohara Y, Izui S.Author information Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland;AbstractIgG bears asparagine-linked oligosaccharide side chains in the Fc region. Variations in their extent of galactosylation and sialylation could modulate IgG Fc-dependent effector functions, and hence Ab activity. However, it has not yet been clarified whether the pathogenic potential of IgG autoantibodies is consistently enhanced by the absence of galactose residues per se or the lack of terminal sialylation, which is dependent on galactosylation. Moreover, it remains to be defined whether the increased pathogenicity of agalactosylated IgG is related to activation of the complement pathway by mannose-binding lectin, as suggested by in vitro studies. Using a murine model of autoimmune hemolytic anemia, we defined the contribution of galactosylation or sialylation to the pathogenic activity of IgG1 and IgG2a anti-erythrocyte class-switch variants of 34-3C monoclonal autoantibody. We generated their degalactosylated or highly sialylated glycovariants and compared their pathogenic effects with those of highly galactosylated or desialylated counterparts. Our results demonstrated that lack of galactosylation, but not sialylation, enhanced the pathogenic activity of 34-3C IgG1, but not IgG2a autoantibodies. Moreover, analysis of in vivo complement activation and of the pathogenic activity in mice deficient in C3 or IgG FcRs excluded the implication of mannose-binding lectin-mediated complement activation in the enhanced pathogenic effect of agalactosylated IgG1 anti-erythrocyte autoantibodies.
• Journal of immunology (Baltimore, Md. : 1950).J Immunol.2014 Jan 15;192(2):581-8. doi: 10.4049/jimmunol.1302488. Epub 2013 Dec 13.
• IgG bears asparagine-linked oligosaccharide side chains in the Fc region. Variations in their extent of galactosylation and sialylation could modulate IgG Fc-dependent effector functions, and hence Ab activity. However, it has not yet been clarified whether the pathogenic potential of IgG autoantibo
• PMID 24337750

• Predominantly periventricular necrotizing encephalitis due to toxoplasmosis: two unusual cases and review of literature.

• Lummus S, Kleinschmidt-Demasters BK.AbstractVentriculitis or periventriculitis as a predominant pattern of tissue involvement in cerebral toxoplasmosis was always a rare event, even at the height of the acquired immunodeficiency syndrome (AIDS) era. Ventriculitis on premortem neuroimaging or at autopsy in AIDS patients chiefly led to differential diagnoses of primary central nervous system lymphoma (PCNSL) or cytomegalovirus ventriculitis, not toxoplasmosis. Usually cerebral toxoplasmosis manifests as multifocal, necrotizing, hemorrhagic foci of cerebritis or abscesses. We report two non-AIDS patients with cerebral toxoplasmosis that presented with predominant ventriculitis/periventriculitis, with diagnosis in both cases made only at postmortem examination. A 90-year-old woman, with autoimmune hemolytic anemia and large granular lymphocytic leukemia diagnosed 2 1/2 years prior, presented with altered mental status. Neuroimaging revealed a necrotic 5.4 × 4.6 × 3.5 cm mass extending across corpus callosum and involving both periventricular frontal horn regions, diagnosed as "butterfly" glioblastoma or possible PCNSL. No consideration of infection was raised, care was withdrawn. A 44-year-old woman with systemic lupus erythematous (SLE) treated with prednisone presented with fever and generalized malaise with rapid progression to agitation and confusion. Infection was suspected, but never confirmed on extensive premortem workup. Brain autopsy in both patients revealed severe necrotizing toxoplasmosis virtually confined to periventricular regions. In the first case, necrosis extended across the corpus callosum. Large numbers of organisms were found microscopically, reflecting their immunocompromised, and untreated, status. Cerebral toxoplasmosis should be included in the differential diagnosis when encountering patients with necrotizing ventriculitis, even in the non-AIDS immunosuppressed population.
• Clinical neuropathology.Clin Neuropathol.2014 January/February;33(1):29-37.
• Ventriculitis or periventriculitis as a predominant pattern of tissue involvement in cerebral toxoplasmosis was always a rare event, even at the height of the acquired immunodeficiency syndrome (AIDS) era. Ventriculitis on premortem neuroimaging or at autopsy in AIDS patients chiefly led to differen
• PMID 23993307

Japanese Journal

• 慢性特発性寒冷凝集素症に合併した上腸間膜動脈閉塞症の1例

• 廣野 玄,窪田 智之,舶越 和博,渡辺 卓也,長谷川 勝彦,曽我 憲二,柴崎 浩一
• 日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 108(5), 791-798, 2011-05-05
• 64歳男性．以前より寒冷凝集素症と診断され，冬季になると四肢末梢のチアノーゼやレイノー症状を自覚していた．これらの症状に加え，上腹部痛を繰り返すようになり来院．CTおよび腹部血管造影にて上腸間膜動脈閉塞症と診断され，寒冷凝集素症もその一因と考えられた．寒冷凝集素症は溶血性貧血の他，血球凝集による動脈閉塞症をきたすことがあり，腹痛を訴える場合には上腸間膜動脈閉塞症も念頭に置く必要があると考えられた．
• NAID 10030297387

• 寒冷凝集素症と赤芽球系造血の著明な減少を呈したhairy cell leukemia

• 湯田 淳一朗,本間 りこ,大本 英次郎
• 血液内科 62(4), 530-534, 2011-04
• NAID 40019064517

Related Links

• Cold agglutinin disease - Wikipedia, the free encyclopedia

Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells. It is a form of autoimmune hemolytic anemia, specifically one in ...

• Cold Agglutinin Disease - Medscape Reference

25 Jan 2013 ... Cold agglutinin disease is a form of autoimmune hemolytic anemia caused by cold-reacting autoantibodies. Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) ...

Related Pictures

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★リンクテーブル★

リンク元	「溶血性貧血」「寒冷凝集素症」
関連記事	「disease」「cold」「COLD」「agglutinin」

「溶血性貧血」

　　[★]

英

hemolytic anemia

同

溶血性黄疸 hemolytic jaundice

関

貧血

溶血の種類	機序	脾腫	ヘモグロビン尿 ヘモジデリン尿	疾患
血管外溶血	Mφで貪食される	＋	－	球状赤血球症 HS 自己免疫性溶血性貧血 AIHA (温式) ↑冷式より多い
血管内溶血	血管内で溶血	－	＋	自己免疫性溶血性貧血 AIHA (冷式) 発作性夜間ヘモグロビン尿症 PNH G6PD欠損症 赤血球破砕症候群 不適合輸血

概念

• 赤血球寿命が種々の原因により短縮することに伴う貧血の総称。

病因

• 赤血球が何らかの原因により破壊され、骨髄の代償能力を超えて赤血球が減少することにより貧血を呈する。　→　溶血が存在するが貧血ではない状態がある。
• 溶血の原因

• 先天性疾患

• 遺伝性球状赤血球症(70%)
• 遺伝性楕円赤血球症
• ヘモグロビン異常症、酵素欠乏症

• 後天性疾患

• 自己抗体による溶血

• 自己免疫性溶血性貧血(温式抗体、冷式抗体)、発作性夜間ヘモグロビン尿症、赤血球破砕症候群

HIM.653

赤血球内の素因

• 1. ヘモグロビンの異常
• 2. 膜-細胞骨格複合体の異常

• 遺伝性球状赤血球症(溶血性貧血のなかで一般的なもの。赤血球の細胞膜蛋白・細胞骨格の異常により球状となり脾臓で捕捉され溶血する)、hereditary elliptocytosis HE
• stomatocytosis

• 3. 代謝経路

• 解糖系の異常：pyruvate kinase deficiency
• 還元系の異常：glucose 6-phosphate dehydrogenase deficiency
• 核酸異化異常：pyrimidine 5'-nucleotidase deficiency

赤血球外の素因

• 先天性

• 家族性溶血尿毒症 familial hemolytic uremic syndrome

• 後天性

• 赤血球の機械的損傷
• 毒物・薬物
• 感染
• 自己免疫性溶血性貧血 AIHA

• 発作性寒冷血色素尿症 paroxysmal cold hemoglobinuria PCH
• 寒冷凝集素症 cold agglutinin disease CAD

• 発作性夜間血色素尿症 PNH

症状

• 貧血、無胆汁色素尿性または溶血性黄疸、脾腫

参考

• [charged]Extrinsic nonimmune hemolytic anemia due to mechanical damage: Fragmentation hemolysis and hypersplenism - uptodate

http://www.uptodate.com/contents/extrinsic-nonimmune-hemolytic-anemia-due-to-mechanical-damage-fragmentation-hemolysis-and-hypersplenism?source=search_result&selectedTitle=2%7E150

「寒冷凝集素症」

　　[★]

英

cold agglutinin disease CAD

同

寒冷赤血球凝集素症 cold-hemagglutinin disease CHAD、寒冷凝集素病

関

寒冷凝集素、自己免疫性溶血性貧血

[show details]

寒冷凝集素症 : 約 4,800 件
寒冷凝集素病 : 67 件

• 自己免疫性溶血性貧血の原因の約20%を占める病態

病因

• 寒冷凝集素の出現

• 急性型：先行感染症(マイコプラズマ肺炎、伝染性単核球症)

国試

• 102D046

「disease」

　　[★]

• n.

疾患：illnessより厳密な概念。「ある臓器に明確な障害が確認され、それによって症状が出ているとはっきり説明できる場合」 (PSY.9)

特定の原因、病態生理、症状、経過、予後、病理組織所見が全てそろった場合 (PSY.9)

• something that is very wrong with people's attitudes, way of life or with society.

関

ail、ailment、disease entity、disorder、ill、illness、malady、sick、sickness

• 注意

disease ≠ illness ≠ disorder

　 　 　

「cold」

　　[★]

• adj.

• 寒い、冷たい、寒気がする。冷やした、冷えた(opp.hot)。加熱せずに処理する
• 冷たくなった、死んでいる
• 冷静な。冷淡な。よそよそしい。(やっと抑えている)激しい(怒り)。不感症の。気を滅入らせる、寒々とした
• 興ざましの、つまらない。気乗りのしない。(味が)弱い
• 客観的な(事実)

　 　 　 　 　 　 　 　 　 　 　 　 　 　 　 　

「COLD」

　　[★]

同

chronic obstructive lung disease, 慢性閉塞性肺疾患

「agglutinin」

　　[★]

• n.

• 凝集素、アグルチニン