Enhanced formation of giant cells in common variable immunodeficiency: Relation to granulomatous disease.

Peripheral monocytes from patients with common variable immunodeficiency (CVID) had on average a 2 fold greater tendency to form giant cells in medium without additional cytokines. Giant cell formation was faster and 3 to 5 fold higher in most CVID cells compared to normal. Addition of IL4, GMCSF, IFNγ, TNFa and both T cell and monocyte conditioned media promoted monocyte fusion of some CVID individuals over 5 fold the normal average level, with combinations of cytokines and monokines acting synergistically. The reduction of normal giant cell formation by anti-IFNγ antibody and a greater tendency of CVID cells to fuse in immunoglobulin conditioned media suggests that standard IVIg treatment contributes to granuloma formation. CVID and normal giant cells expressed similar levels of phenotypic molecules and had similar phagocytic activity. Monocytes from many CVID patients have an elevated tendency to fuse which may explain the high incidence of granulomatous complications in CVID

Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity

Background: The actin-interacting protein WD repeat–containing protein 1 (WDR1) promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have been identified recently in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. Objective: Given the pleiotropic expression of WDR1, here we investigated to what extent it might control the lymphoid arm of the immune system in human subjects. Methods: Histologic and detailed immunologic analyses were performed to elucidate the role of WDR1 in the development and function of B and T lymphocytes. Results: Here we identified novel homozygous and compound heterozygous WDR1 missense mutations in 6 patients belonging to 3 kindreds who presented with respiratory tract infections, skin ulceration, and stomatitis. In addition to defective adhesion and motility of neutrophils and monocytes, WDR1 deficiency was associated with aberrant T-cell activation and B-cell development. T lymphocytes appeared to develop normally in the patients, except for the follicular helper T-cell subset. However, peripheral T cells from the patients accumulated atypical actin structures at the immunologic synapse and displayed reduced calcium flux and mildly impaired proliferation on T-cell receptor stimulation. WDR1 deficiency was associated with even more severe abnormalities of the B-cell compartment, including peripheral B-cell lymphopenia, paucity of B-cell progenitors in the bone marrow, lack of switched memory B cells, reduced clonal diversity, abnormal B-cell spreading, and increased apoptosis on B-cell receptor/Toll-like receptor stimulation. Conclusion: Our study identifies a novel role for WDR1 in adaptive immunity, highlighting WDR1 as a central regulator of actin turnover during formation of the B-cell and T-cell immunologic synapses

7th Drug hypersensitivity meeting: part two

No abstract availabl

Vitamin D and the immune system: Medical education [Vitamin D ve i·mmün sistem]

Vitamin D plays important role in calcium homeostasis and bone metabolism. However, the researches performed during the past twenty years revealed that it also has a significant immunomodulatory effect. D vitamin deficiency has been shown to be related to increased tendency for development of several autoimmune diseases such as type 1 diabetes and inflammatory bowel diseases. D vitamin deficiency has also been associated with increased risk of development of infections such as tuberculosis and malignancy. In experimental models, it has been found to be successful in reducing the risk of graft rejection. D vitamin has been found to have salutary effects on renal allograft function. The findings of the researches indicate that vitamin D might have a role as an alternative and safer treatment modality in many autoimmune diaseases and transplantation practice. Copyright © 2008 by Türkiye Klinikleri