Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: A mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies

被引：54

作者：

Bayry, Jagadeesh ^{[1
,2
,3
]}

Fournier, Emilie M. ^{[3
,4
]}

Maddur, Mohan S. ^{[2
,3
]}

Vani, Janakiraman ^{[2
,3
]}

Wootla, Bharath ^{[2
,3
]}

Siberil, Sophie ^{[2
,3
]}

Dimitrov, Jordan D. ^{[2
,3
]}

Lacroix-Desmazes, Sebastien ^{[2
,3
]}

Berdah, Mikael ^{[5
]}

Crabol, Yoann ^{[6
]}

Oksenhendler, Eric ^{[7
]}

Levy, Yves ^{[5
,8
,9
]}

Mouthon, Luc ^{[6
,10
]}

Sautes-Fridman, Catherine ^{[3
,4
]}

Hermine, Olivier ^{[11
,12
]}

Kaveri, Srini V. ^{[2
,3
]}

机构：

[1] Ctr Rech Cordeliers, INSERM, U872, UMRS 872, F-75006 Paris, France

[2] Univ Paris 06, Ctr Rech Cordeliers, Unite Mixte Rech Sante 872, Equipe 16, F-75006 Paris, France

[3] Univ Paris 05, Unite Mixte Rech Sante 872, F-75006 Paris, France

[4] Ctr Rech Cordeliers, Unite Mixte Rech Sante 872, Equipe 13, F-75006 Paris, France

[5] AP HP, Grp Henri Mondor Albert Chenevier, Immunol Clin, F-94010 Creteil, France

[6] Univ Paris 05, AP HP, Ctr Reference Malad Syst Autoimmunes Rares, F-75006 Paris, France

[7] Hop St Louis, AP HP, Dept Clin Immunol, F-75010 Paris, France

[8] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France

[9] Fac Med, F-94010 Creteil, France

[10] Inst Cochin, INSERM, U1016, Paris, France

[11] Univ Paris 05, CNRS, UMR 8147, Fac Med Necker, F-75270 Paris, France

[12] Hop Necker Enfants Malad, AP HP, Serv Hematol, F-75015 Paris, France

来源：

JOURNAL OF AUTOIMMUNITY | 2011年 / 36卷 / 01期

关键词：

IN-VIVO MODULATION; DENDRITIC CELLS; T-CELLS; AUTOIMMUNE-DISEASES; INFECTIOUS-DISEASES; IMMUNE-DEFICIENCY; LYMPHOCYTES; THERAPY; MUTATIONS; TACI;

D O I：

10.1016/j.jaut.2010.09.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial effects of IVIg in primary immunodeficiencies are not completely understood. Therefore we investigated the effect of 'replacement dose' of IVIg by probing its action on B cells from CVID patients. We demonstrate that IVIg at low doses induces proliferation and immunoglobulin synthesis from B cells of CVID patients. Interestingly. B cell stimulation by IVIg is not associated with induction of B cell effector cytokine IFN-gamma and of transcription factor T-bet. Together, our results indicate that in some CVID patients, IVIg rectifies the defective signaling of B cells normally provided by T cells and delivers T-independent signaling for B cells to proliferate. IVIg 'replacement therapy' in primary immunodeficiencies is therefore not a merepassive transfer of antibodies to prevent exclusively the recurrent infections; rather it has an active role in regulating autoimmune and inflammatory responses through modulating B cell functions and thus imposing dynamic equilibrium of the immune system. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：9 / 15

页数：7

共 65 条

[31] The genetics and epigenetics of autoimmune diseases [J].