Raised levels of immunoglobulin G, A and M are associated with an increased risk of total and cause-specific mortality: the Vietnam Experience Study

BACKGROUND: Immunoglobulins (Ig) are essential for combating infectious disease. However, high levels are associated with a range of diseases and/or poor health behaviours, such as autoimmune diseases, chronic infection, HIV and excessive alcohol consumption. In the present analyses, we extend this body of work by examining whether higher levels of serum Ig G, A and M are associated with increased mortality risk.

METHODS: Participants were 4255 Vietnam-era, former US army personnel (the Vietnam Experience Study). From military service files, telephone interviews in 1983 and a medical examination in 1986, sociodemographic, and health data were collected. Contemporary morning fasted blood samples were taken from which IgG, IgA and IgM concentrations were determined. Mortality surveillance over 15 years gave rise to deaths ascribed to all-causes, cardiovascular disease mortality, all cancers combined mortality, external cause and 'other' causes (predominantly comprising deaths due to infectious disease). Cox proportional hazard models were utilised to compute HRs per SD increase in Ig which were first adjusted for age and then additionally adjusting for a range of candidate confounders.

RESULTS: In multiply adjusted analyses, in general, the higher the immunoglobulin concentration, the greater the risk of death. Thus, IgA (HR=2.0 95% CI 1.47 to 2.73), IgM (HR=1.5 95% CI 1.11 to 1.91) and IgG (HR=5.8 95% CI 3.38 to 9.95) were positively related to all-cause mortality. Corresponding results for 'other' causes of mortality were 4.7 (2.64 to 8.19), 3.5 (2.29 to 5.45) and 33.4 (15.13 to 73.64).

CONCLUSIONS: In the present study, high levels of Ig are associated with an elevated risk of death from total and 'other' causes, mainly infectious disease. High levels of Ig, particularly IgG, may signal subclinical disease.