Clinical significance of serum IgG4 concentrations

Abstract

IgG4 is the least abundant and least known subclass of immunoglobulin-G. It has been related with a protective role in IgE-mediated reactions and with the recently described IgG4-related disease, which is characterized by fibroinflammatory pseudotumours and high serum IgG4 concentrations. The aim of this thesis is to evaluate the clinical significance of serum IgG4 concentrations. Firstly, we perform a literature review of IgG4-related disease. Secondly, we investigate the distribution of serum IgG4 concentrations in a general adult population and its relation with the remaining immunoglobulins, particularly IgE and IgD. Thirdly, we investigate both specific and total serum IgG4 concentrations in patients heavily exposed to a given allergen (beekeepers). Finally, we evaluate the clinical implications of serum IgG4 determinations in a large sample of hospital patients. The main conclusions of our work are: - Serum IgG4 concentrations in the general adult population show wide variation. A small proportion of individuals (around 1%) exhibit serum IgG4 concentrations higher than 135 mg/dL, the usual threshold for IgG4-related disease criteria. - Serum IgG4 concentrations in adults are higher in males than in females and decrease with ageing. - Serum IgG4 concentrations in adults are not significantly influenced by alcohol consumption, smoking or common metabolic abnormalities (obesity and the related metabolic syndrome). - Serum IgG4 concentrations tend to be higher in atopics (individuals with IgE-mediated sensitization to aeroallergens) than in non-atopics, particularly among atopics without respiratory symptoms. - Serum IgG4 concentrations in adults are significantly correlated with those of IgE and IgD. The correlation of IgG4 with IgE is particularly evident in non-atopics, whereas the correlation of IgG4 with IgD is particularly evident in atopics. - Individuals who are heavily exposed to a given allergen (beekeepers exposed to honeybee venom) show high serum concentrations of honeybee venom-specific IgG4 in relation to tolerance. This specific IgG4 represents a sizeable proportion of total serum IgG4. However, this heavy exposure does not significantly influence total serum IgG4. - In absence of either evidence or suspicion of IgG4-related disease, measurement of total serum IgG4 concentrations seems to be of limited value in standard clinical practice. Taken together, these results are consistent, from a mechanistic standpoint, with a tolerogenic effect of IgG4 in allergic disease. From a clinical standpoint, these results indicate that both gender and age should be taken into account when interpreting serum IgG4 concentrations in clinical settings.