1050

Abstract

Introduction: Low levels of IgG have been associated with poor outcome in sepsis; however, previous studies focused only on small cohorts of patients. Also, few data are available on the evolution of immunoglobulin levels over time. The aim of this study was to evaluate the incidence of hypogammaglobulinemia and their prognostic value in a large cohort of septic patients. Methods: This is a nested case-control study of the multicenter, randomized ALBIOS trial that enrolled patients with severe sepsis or septic shock in 100 ICUs in Italy. We selected 150 septic shock patients (75 survivors and 75 non-survivors on ICU discharge) matched for age, sex, center and treatment assignment. We excluded patients with immunosuppressive therapy or with cancer. EDTA-plasma samples were collected at days 1, 2 and 7 after enrolment to assay IgG, IgA and IgM in a central laboratory using nephelometry testing. Low concentrations of gammaglobulins were defined as less than 650 mg/dL for IgG, less than 70 mg/dL for IgA, and less than 40 mg/dL for IgM. Results: Eighty-three patients (55%) had low IgG concentrations, 12 had low IgA concentrations (8%), and 43 had low IgM concentrations (29%). Median IgG, IgA and IgM concentrations significantly increased over time (p<0.001), and 61 (41%), 1 (1%) and 17 (11%) still had low-IgG, low-IgA and low-IgM on day 7, respectively. Hypo-IgG and hypo-IgA on admission were less frequent in non-survivors than survivors (34/75 vs. 49/75, p=0.01 and 2/75 vs. 10/75, p=0.01, respectively) Mortality was significantly lower in patients with low-IgG (34/83 vs. 41/67, p=0.02) and low IgA (2/12 vs. 73/138, p=0.02) on admission when compared to those with normal Ig levels. IgG and IgA levels were significantly higher in non-survivors than survivors over time, especially on day 1 and 2 since admission (p<0.05). Interestingly, ICU mortality was significantly higher in those patients in the highest quartile of distribution for IgG levels (ranges: 779-2063 mg/dl) on admission (p=0.01). No association of outcome with IgM was found. Conclusions: In this cohort of septic patients with at least one-week survival, low levels of IgG were common on ICU admission but tended to resolve over time. Mortality was higher in those patients with the highest levels of IgG. No impact of IgM levels was found on outcome.