WordNet

a disturbance in the synthesis of immunoglobulins; proteins having antibody activity increase greatly in the blood

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/03 21:56:53」(JST)

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Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin.

It is a type of immunoproliferative disorder.

Types[edit]

Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglobulin in the blood serum.^[1] The name of the disorder refers to the position of the excess of proteins after serum protein electrophoresis (found in the gammaglobulin region).

Most hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), because this is the default immunoglobulin type prior to class switching. Some types of hypergammaglobulinemia are actually caused by a deficiency in the other major types of immunoglobulins, which are IgA, IgE and IgG.

There are 5 types of hypergammaglobulinemias associated with hyper IgM.^[2]

MeSH considers hyper IgM syndrome to be a form of dysgammaglobulinemia, not a form of hypergammaglobulinemia .

Type 1[edit]

X-linked immunodeficiency with hyper–immunoglobulin M, which is also called type 1 hyper IgM, is a rare form of primary immunodeficiency disease caused by a mutation in the Tumor Necrosis Factor Super Family member 5 (TNFSF5) gene, which codes for CD40 ligand. This gene is located on the long arm of the X chromosome at position 26, denoted Xq26.^[3] Normally, CD40 ligand is expressed on activated T cells, and is necessary to induce immunoglobulin class switching from IgM to the other immunoglobulin types. It does this by binding to its ligand, CD40, which is found expressed on the surface of B cells.^[4] The mutation in the TNFSF5 gene causes there to be no recognition of CD40 by CD40 ligand, and thus the T cells do not induce Ig class switching in B cells, so there are markedly reduced levels of IgG, IgA, and IgE, but have normal or elevated levels of IgM. CD40 ligand is also required in the functional maturation of T lymphocytes and macrophages, so patients with this disorder have a variable defect in T-lymphocyte and macrophage effector function, as well as hyper IgM.^[4]

Type 2[edit]

Immunodeficiency with hyper IgM type 2 is caused by a mutation in the Activation-Induced Cytidine Deaminase (AICDA) gene, which is located on the short arm of chromosome 12. The protein that is encoded by this gene is called Activation-Induced Cytidine Deaminase (AICDA) and functions as a DNA-editing deaminase that induces somatic hypermutation, class switch recombination, and immunoglobulin gene conversion in B cells.^[5] When a person is homozygous for the mutation in the AICDA gene, the protein fails to function, and thus somatic hypermutation, class switch recombination, and immunoglobulin gene conversion cannot occur, which creates an excess of IgM.^[2]

Type 3[edit]

Immunodeficiency with hyper IgM type 3 is caused by a mutation in the gene that codes for CD40. As mentioned above, CD40 is expressed on the surface of B cells, and its binding to CD40 ligand on activated T cells induces Ig class switching.^[4] When the mutation is present, there is no signal for B cells to undergo class switching, so there is an excess of IgM and little to no other immunoglobulin types produced.^[2]

Type 4[edit]

Immunodeficiency with hyper IgM type 4 is poorly characterized. All that is known is that there is an excess of IgM in the blood, with normal levels of the other immunoglobulins. The exact cause is yet to be determined.^[2]

Type 5[edit]

Immunodeficiency with hyper IgM type 5 is caused by a mutation in the Uracil-DNA glycosylase (UNG) gene, which, like AICDA, is located on chromosome 12. This codes for Uracil DNA Glycosylase, which is responsible for excising previous uracil bases that are due to cytosine deamination, or previous uracil misincorporation from double-stranded previous DNA substrates. This enzyme is also responsible for helping with gene conversion during somatic recombination in B cells. The mutation in the gene causes an enzyme that does not function properly, thus gene conversion does not proceed and class switching cannot occur.^[2]

References[edit]

^ Health Communication Network. Immunoproliferative disorders- Topic Tree. http://www.use.hcn.com.au/subject.%60Immunoproliferative%20Disorders%60/home.html. Accessed March 2007.
^ ^a ^b ^c ^d ^e Online 'Mendelian Inheritance in Man' (OMIM) Immunodeficiency with hyper IgM -308230
^ Park LC X-linked Immunodeficiency with hyper IgM at eMedicine
^ ^a ^b ^c Lichtman, Andrew H.; Abbas, Abul K. (2003). Cellular and molecular immunology (5th ed.). Philadelphia: Saunders. ISBN 0-7216-0008-5.
^ Noguchi E, Shibasaki M, Inudou M, et al. (2001). "Association between a new polymorphism in the activation-induced cytidine deaminase gene and atopic asthma and the regulation of total serum IgE levels". J. Allergy Clin. Immunol. 108 (3): 382–6. doi:10.1067/mai.2001.117456. PMID 11544457.

UpToDate Contents

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English Journal

Spatial Alterations between CD4+ T Follicular Helper, B, and CD8+ T Cells during Simian Immunodeficiency Virus Infection: T/B Cell Homeostasis, Activation, and Potential Mechanism for Viral Escape.

Hong JJ, Amancha PK, Rogers K, Ansari AA, Villinger F.SourceDivision of Pathology, Yerkes National Primate Research Center, Atlanta, GA 30329.
Journal of immunology (Baltimore, Md. : 1950).J Immunol.2012 Mar 2. [Epub ahead of print]
HIV/SIV infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. Moreover, lymph nodes have been highlighted as a predilection site for SIV escape in vivo. Followin
PMID 22387550

Requirement of myeloid cell-specific Fas expression for prevention of systemic autoimmunity in mice.

Cuda CM, Agrawal H, Misharin AV, Haines GK 3rd, Hutcheson J, Weber E, Schoenfeldt JA, Mohan C, Pope RM, Perlman H.SourceNorthwestern University Feinberg School of Medicine, Chicago, Illinois.
Arthritis and rheumatism.Arthritis Rheum.2012 Mar;64(3):808-20. doi: 10.1002/art.34317.
OBJECTIVE: The death receptor Fas is a critical mediator of the extrinsic apoptotic pathway, and its role in mediating lymphoproliferation has been extensively examined. The present study was undertaken to investigate the impact of myeloid cell-specific loss of Fas.METHODS: Mice with Fas flanked by
PMID 22143975

Japanese Journal

Splenectomy prolongs the effects of corticosteroids in mouse models of autoimmune hepatitis.

Maruoka Ryutaro,Aoki Nobuhiro,Kido Masahiro,Iwamoto Satoru,Nishiura Hisayo,Ikeda Aki,Chiba Tsutomu,Watanabe Norihiko
Gastroenterology 145(1), 209-220.e9, 2013-07-00
… Neonatal C57BL/6 PD-1^{–/–} mice that underwent thymectomy developed chronic hepatitis with fibrosis and hypergammaglobulinemia and produced antinuclear antibodies; …
NAID 120005315980

Castleman's Disease Accompanied by Hypolipidemic Cerebral Hemorrhage and Nephrosclerosis

Imafuku Aya,Suwabe Tatsuya,Hasegawa Eiko,Mise Koki,Sumida Keiichi,Hiramatsu Rikako,Yamanouchi Masayuki,Hayami Noriko,Hoshino Junichi,Sawa Naoki,Oohashi Kenichi,Fujii Takashi,Okubo Minoru,Takaichi Kenmei,Oga Tatsuhide,Ubara Yoshifumi
Internal Medicine 52(14), 1611-1616, 2013
… A 56-year-old Japanese man developed a cerebral hemorrhage and was diagnosed with plasma cell-type multicentric Castleman's disease (MCD) based on the findings of an inguinal lymph node biopsy in addition to clinical findings, including hypergammaglobulinemia, anemia and elevation of the levels of CRP and serum IL-6. … Following the initiation of treatment with anti-interleukin-6 receptor antibodies, the hypergammaglobulinemia, anemia, CRP level and serum lipid profile improved. …
NAID 130003365708

Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 4-year analysis in Japanese.

Terao Chikashi,Ohmura Koichiro,Yamamoto Keiichi,Yukawa Naoichiro,Kawabata Daisuke,Nojima Takaki,Fujii Takao,Mimori Tsuneyo
Modern rheumatology 22(3), 426-430, 2012-06-01
… Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. …
NAID 10030782345

Related Pictures

★リンクテーブル★

リンク元	「免疫グロブリン」「高γグロブリン血症」「gammopathy」「hyperimmunoglobulinemia」
拡張検索	「Waldenstrom hypergammaglobulinemia」「monoclonal hypergammaglobulinemia」「polyclonal hypergammaglobulinemia」「Waldenstrom's hypergammaglobulinemia purpura」

「免疫グロブリン」

Hypergammaglobulinemia
	Classification and external resources
ICD-10	D89.0, D89.2
ICD-9	289.89
MeSH	D006942

　　[★]

英: immunoglobulin, Ig
同: 抗体
商: HBグロブリン、ヴェノグロブリン、ガンマーグロブリン、ガンマガード、ガンマグロブリン、グロブリン、グロベニン-I、サイモグロブリン、サングロポール、ゼットブリン、テタノセーラ、テタノブリン、テタノブリンIH、はぶ抗毒素、ヒスタグロビン、ベニロン-I、ヘパトセーラ、ヘブスブリン、ヘブスブリンIH、ポリグロビン、まむし抗毒素、抗Dグロブリン、抗D人免疫グロブリン、抗HBs人免疫グロブリン、破傷風グロブリン
関: 免疫、T細胞受容体、リンパ球抗原受容体; IgM、IgD、IgG、IgA、IgE

構造

H鎖とL鎖からなり、Igドメインをそれぞれ4つ(IgMとIgEは5つ)、2つもつ。

胎児の免疫グロブリン

胎児は母胎より免疫グロブリンをもらうが、生後六ヶ月で消失する (標準予防策実践マニュアル南江堂第2刷 p.12)
自分で抗体を作る能力は3-6歳で完成する (標準予防策実践マニュアル南江堂第2刷 p.12)

免疫グロブリンの特性 (IMM.161)

抗体	IgG₁	IgG₂	IgG₃	IgG₄	IgM	IgA₁	IgA₂	IgD	IgE
重鎖	γ₁	γ₂	γ₃	γ₄	μ	α₁	α₂	δ	ε
分子量	146	146	165	146	970	160	160	184	188
補体活性化(古典的経路)	++	+	+++	-	++++	-	-	-	-
補体活性化(代替経路)	-	-	-	-	-	+	-	-	-
胎盤通過	+++	+	++	±	-	-	-	-	-
食細胞FcRへの結合	+	-	+	±	-	+	+	-	+
肥満細胞・好塩基球への結合	-	-	-	-	-	-	-	-	+++
staphylococcal Protein Aとの反応性	+	+	±	+	-	-	-	-	-

免疫グロブリンの遺伝子再構成 (IMM.144)

多様性の獲得機構

多数のV遺伝子
VJとJDV遺伝子の組み換え
組み換え時の不正確性(塩基欠損、付加、N塩基)(CDR3)
体細胞突然変異(CDR1,CDR2)
H鎖とL鎖の組み合わせ

シグナル伝達

基準値

小児基準値研究班(編)：日本人小児の臨床検査基準値。日本公衆衛生協会、1997

SPE.704

	IgG		IgA		IgM
	♂	♀	♂	♀	♂	♀
1ヶ月	400 ～ 1030		ー～ 24		21 ～ 96
6ヶ月	290 ～ 950		8 ～ 50		46 ～ 176
1歳	460 ～ 1220	470 ～ 1210	16 ～ 128	14 ～ 98	57 ～ 260	81 ～ 314
3歳	530 ～ 1340	540 ～ 1340	25 ～ 174	22 ～ 150	63 ～ 279	86 ～ 332
6歳	630 ～ 1490	650 ～ 1530	45 ～ 258	38 ～ 238	72 ～ 305	92 ～ 353
12歳	750 ～ 1660	790 ～ 1740	71 ～ 352	63 ～ 373	72 ～ 306	100 ～ 380
成人	680 ～ 1620		84 ～ 438		380 ～ 1620