Hyper Immunoglobulin M Immunodeficiency (Dysgammaglobulinemia)

Geha, Raif S.; Hyslop, Newton; Alami, Samih Y.; Farah, Fuad S.; Schneeberger, Eveline E.; Rosen, Fred S.

doi:10.1172/jci109473

Cited by 83 publications

(8 citation statements)

References 15 publications

(25 reference statements)

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“…Thus, the limited number of studies of in vitro T cell-proliferative responses to specific antigens have revealed either normal responses to tetanus toxoid or lectins or reduced responses to various antigens, which generally are corrected with booster immunization (11,44,45). In this regard, two of the three patients tested in our series demonstrate normal delayed-type skin test responses without booster immunization (one to tetanus, one to candida and mumps).…”

mentioning

confidence: 66%

Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome

Jain¹,

Atkinson²,

Lipsky³

et al. 1999

J. Clin. Invest.

105

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confidence: 66%

Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome

Jain¹,

Atkinson²,

Lipsky³

et al. 1999

J. Clin. Invest.

105

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“…Engagement of CD40 on B cells by CD40L or by monoclonal antibody [I 127851 (mAb) results in B cell activation, proliferation, aggregation, and immunoglobulin isotype switching [4,6,[9][10][11][12][13]. Soluble forms of CD40 (sCD40) inhibit T cell-dependent B cell activation and immunoglobulin isotype switching [14].We [15, 161 and others [17-201 have recently reported that a defect in the gene encoding CD40L is responsible for X-linked immunoglobulin deficiency with normal or elevated IgM (X-linked hyper IgM).These patients are unable to synthesize immunoglobulins other than IgM or IgD [21,221, suggesting that interaction between CD40 on B cells and its ligand on activated T cells is critical for immunoglobulin isotype switching. Expression of CD40L in T cells is tightly regulated [23].…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of the ligand for CD40 in newborn lymphocytes

1994

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Immune responses in newborn lymphocytes show a defect in isotype switching from IgM to IgG and IgA. Immunoglobulin isotype switching in B lymphocytes requires a contact-dependent signal from T lymphocytes which is delivered by the ligand for the B cell surface antigen CD40. We investigated the capacity of newborn lymphocytes to express the CD40 ligand and to undergo CD40 ligand-dependent immunoglobulin isotype switching. After stimulation by phorbol ester and ionomycin, newborn lymphocytes expressed markedly decreased amounts of CD40 ligand on their surface compared to normal adult lymphocytes. Northern blot analysis of mRNA derived from activated cord blood lymphocytes also revealed markedly decreased amounts of CD40 ligand mRNA. Decreased expression of CD40 ligand in newborn lymphocytes was associated with a severely decreased ability to undergo T cell-dependent immunoglobulin isotype switching. Newborn lymphocytes synthesized little or no detectable IgE in response to T cell-dependent stimulation by interleukin-4 but synthesized IgE in response to T cell-independent stimulation by CD40 monoclonal antibody and interleukin-4. These results indicate that decreased expression of CD40 ligand in newborn lymphocytes may be the underlying cause of deficient immunoglobulin isotype switching in newborns.

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“…Affected males are unduly susceptible to recurrent pyogenic infections, autoimmune diseases, and lymphoproliferative disease. The underlying defect in these patients appears to be an inability to switch from IgM/IgD secretion to the production of other immunoglobulin isotypes, IgG, IgA, or IgE (8,9). We demonstrate that B cells from three males with this syndrome synthesize IgE in response to CD40 mAb plus IL-4 and undergo deletional switch recombination.…”

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confidence: 80%