EUHM Resident Report: What should you look for when you see a large globulin gap?

In this study, a higher gamma gap (per 1 g/dl) was significantly associated with a higher risk of death from any cause (HR 1.36; 95% CI: 1.10, 1.67; P = 0.005) (Table 3). There was also a significant trend across quartiles of gamma gap (P = 0.04). Similarly, a spline of the association demonstrated a nearly linearly shaped curve with risk being significantly higher above the median value (Fig 2). We examined the association between the gamma gap and specific causes of death. The gamma gap was significantly associated with death from pulmonary causes (per 1 g/dl higher gamma gap, HR 2.22; 95% CI: 1.19, 4.17; P = 0.01), but not cardiovascular disease or cancer. Spline models of the gamma gap showed no association with mortality from cardiovascular disease, a non-significant, positive trend for mortality from cancer, and a significant positive association with mortality from pulmonary disease.

Table 3
Association between gamma gap and all-cause mortality, cardiovascular disease mortality, cancer mortality, pulmonary mortality, and other causes of mortality (Hazard Ratios, 95% CI).

The Gamma Gap and All-Cause Mortality. (2015). PloS One., 10(12), PloS one. , 2015, Vol.10(12).

The “gamma gap” or globulins, i.e. the difference between total serum proteins and albumin measured from a comprehensive metabolic panel, is a frequently used clinical screening tool to assess for latent infection, malignancy, or autoimmune inflammatory diseases. This is based on the observation that albumin accounts for the majority of total serum protein, while with viral infections, plasma cell malignancies, or autoimmune conditions there is an excess of immunoglobulins, raising the total amount of serum protein independent of albumin

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