Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome

Abstract

IntroductionThe aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis.MethodsIn this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages. Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days. Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production.ResultsSerum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock. Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors. Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls.ConclusionsSpecific changes of circulating IgM occur when patients with severe sepsis progress into septic shock. The distribution of IgM is lower among non-survivors.

The role of genetics and antibodies in sepsis

“…Results showed downregulation of pathways associated with activation of both Tand B-lymphocytes (12). These gene profiles are in keeping with our above findings of anergy of lymphocytes of sepsis patients for the production of IgM (11).…”

“…For patients with septic shock, daily IgM measurements were done, starting from the first 24 hours from vasopressors for another 6 days. The body distribution of IgM reflected by the area under curve of IgM over the entire time of follow-up was significantly greater in survivors than in non-survivors both when censoring was done on day 28 or on the day of hospital discharge showing a great body deficit of IgM linked with unfavorable outcome (11). This deficit in the body distribution of IgM was also associated with failure of ex vivo stimulation of circulating lymphocytes by the universal lymphocyte agonist phytohemagglutin for the production of IgM.…”

“…Comparisons between groups based upon disease are done with non-parametric statistics (8)(9)(10)(11). This means that there is an individuality for IG production within each group.…”

Early therapy with IgM-enriched polyclonal immunoglobulin in patients with septic shock

“…Ig has many immunomodulatory effects including neutralising endotoxins, stimulating opsonic and bactericidal activity, reducing pro-inflammatory mediators and increasing anti-inflammatory mediators [6]. Moreover, patients with hypogammaglobulinemia have a high incidence of infections, and a high proportion of patients with severe sepsis and septic shock have low serum levels of Ig, which seems to be associated with a significantly higher mortality rate [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, it is not clear whether patients with sepsis and hypogammaglobulinemia would benefit from the administration of Ig at the currently recommended doses.…”

“…The mechanism of action for Ig therapy is likely multifaceted and could include direct antibacterial and anti-endotoxin activities; reducing the expression of inflammatory mediators or directly scavenging these molecules; and other complex immunomodulatory effects [6]. Clinically, the serum Ig concentrations are generally low in patients with septic shock, and the level and kinetics of serum Ig are related to patient outcome [7,8].…”