Common Variable Immunodeficiency at the End of a Prospering Decade: Towards Novel Gene Defects and Beyond

Hermann Eibel; Ulrich Salzer; Klaus Warnatz

Disclosures

Curr Opin Allergy Clin Immunol. 2010;10(6):526-533. 

In This Article

TLR Signaling Defects in Common Variable Immunodeficiency

For different subgroups of CVID patients it has previously been demonstrated that TLR9 signaling in B cells and plasmacytoid dentritic cells (PDCs) is impaired leading to lower expression of costimulatory molecules and reduced production of proinflammatory cytokines.[45] Now, it has been found that TLR7/8 function is even more impaired in CVID patients than TLR9 function.[46••] Neither CD27 nor CD27+ B cells proliferated in response to Loxoribine. In addition, upregulation of AID and CD27 was ineffective resulting in defective class switch recombination and Ig secretion. Since the addition of exogeneous IFN-α to CVID B cells partially restored the proliferative and class switch recombination responses to Loxoribine and since the production of proinflammatory cytokines by CVID PBMC in response to various TLR ligands were found to be normal[46••] a general defect in TLR signaling, however, seems unlikely.[46••] An additional study[47] confirmed the findings of impaired TLR9 activation in CVID and demonstrated that the stimulation with microbial extracts from Streptococcus pneumoniae and Haemophilus influenzae did result in impaired activation and proliferation.[47] Thus, there is now convincing evidence that dysfunction of several TLRs may be involved in the pathophysiology of CVID. However, genetic defects in or associations with TLR pathways, which could support a causative role of these abnormalities, have not yet been identified in CVID.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....