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

Abstract

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.

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

“…A higher fusion index contributes to formation of granuloma (a lymphoproliferative complication) and is related to chronic inflammation (eg, inflammatory cytokines, particularly IFN-γ and TNF) and lymphocyte concentration. Of note, in vitro, the fusion rate of monocytes treated with immunoglobulin-based products can be increased, thus raising the debate of whether this standard treatment is involved in the risk of granulomatous disease, possibly by enhancing FcγRI expression [78].…”

Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults

“…Another cause that might underlie the development of CD in CVID patients is enhanced granulomas formation in CVID. An increased trend of monocytes forming giant cells has been demonstrated in CVID, which contributed to elevated granulocyte-macrophage colony-stimulating factor, IL−4, IFN-γ, and TNF-α [ 84 , 299 ]. Besides, Scott-Taylor et al reported a greater trend of CVID monocytes fusing in immunoglobulin-conditioned media, which suggest that standard immunoglobulin replacement therapy can contribute to granuloma formation [ 299 ].…”