Physical Characterization and Innate Immunogenicity of Aggregated Intravenous Immunoglobulin (IGIV) in an In Vitro Cell-Based Model.

PURPOSE: To investigate in vitro the innate immune response to accelerated stress-induced aggregates of intravenous immunoglobulin (IGIV) using a well-defined human cell-line model, and to correlate the innate response to physical properties of the aggregates. METHODS: IGIV aggregates were prepared by applying various accelerated stress methods, and particle size, count and structure were characterized. Immune cell activation as tracked by inflammatory cytokines released in response to aggregates was evaluated in vitro using peripheral blood mononuclear cells (PBMC), primary monocytes and immortalized human monocyte-like cell lines. RESULTS: IGIV aggregates produced by mechanical stress induced higher cytokine release by PBMC and primary monocytes than aggregates formed by other stresses. Results with the monocytic cell line THP-1 paralleled trends in PBMC and primary monocytes. Effects were dose-dependent, enhanced by complement opsonization, and partially inhibited by blocking toll-like receptors (TLR2 and TLR4) and to a lesser extent by blocking Fc gamma receptors (FcγRs). CONCLUSIONS: Stress-induced IGIV aggregates stimulate a dose-dependent cytokine response in human monocytes and THP-1 cells, mediated in part by TLRs, FcγRs and complement opsonization. THP-1 cells resemble primary monocytes in many respects with regard to tracking the innate response to IgG aggregates. Accordingly, the measurement of inflammatory cytokines released by THP-1 cells provides a readily accessible assay system to screen for the potential innate immunogenicity of IgG aggregates. The results also highlight the role of aggregate structure in interacting with the different receptors mediating innate immunity.

Chromium induced contact dermatitis and indices for diagnosis.

Chromium exposure plays an important role in development of contact dermatitis. The prevalence of contact dermatitis among tannery workers and cement-exposed workers is high. This study was designed to determine the prevalence of contact dermatitis among some Egyptian workers exposed to chromium and to investigate the role of patch test and IgE immunoassay in diagnosis of contact dermatitis. Eighty-three male workers who were exposed to chromium were selected after application of certain exclusion criteria to be the target population of this study. Forty male workers away from exposure to chromium were taken to be the controls. All the exposed and non exposed workers were investigated through an interview questionnaire, clinical examination, patch test and determination of blood and urine chromium levels, absolute eosinophilic count and total IgE level. The results showed that there was no significant difference between exposed workers with clinically diagnosed contact dermatitis and the clinically free exposed workers regarding age and work duration. 7.7% of exposed workers with positive patch test suffered from contact dermatitis while 31.6% of exposed workers with negative patch test suffered from contact dermatitis. There was no statistically significant difference between clinically diagnosed contact dermatitis workers and clinically free workers regarding blood and urine chromium levels. IgE level and absolute eosinophilic count were statistically higher among exposed workers with contact dermatitis than among clinically free exposed workers. According to the results of this study, it is concluded that the diagnosis of skin hypersensitivity to chromium should depend upon the history of chromium exposure, clinical examination and a battery of investigations including IgE level, eosinophilic count and patch test.