Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis

Bermejo-Martín, Jesús F.; Rodríguez-Fernández, Ana; Herrán-Monge, Rubén; Andaluz‐Ojeda, David; Muriel-Bombín, Arturo; Merino, Pedro; García-García, Marta M.; Citores, Rafael; Gandía, Francisco; Almansa, Raquel; Blanco, Jesús

doi:10.1111/joim.12265

Cited by 85 publications

(79 citation statements)

References 18 publications

(28 reference statements)

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“…While the presence of patients with previous immunosuppression did not alter the predictive ability of total IgG and IgG1, it modified that of IgG2, which was only able to predict ICU mortality in those patients with no previous immunosuppression. These findings reinforce the superiority of the combined immunoglobulin score over immunoglobulins individually considered to identify sepsis patients at risk of poor outcomes [4]. …”

Section: Discussionsupporting

confidence: 72%

“…In addition, patients with the highest IgG levels (fourth quartile) showed a statistically significant higher mortality in a risk-adjusted calculation compared to the reference quartile [3]. A previous report from our group supported that the answer could be in considering immunoglobulin isotypes not as isolated entities but in evaluating their prognostic ability in combination [4, 5]. …”

Section: Introductionmentioning

confidence: 97%

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The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure

Martín‐Loeches¹,

Muriel-Bombín

Ferrer

et al. 2017

Ann. Intensive Care

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BackgroundPre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity.MethodsThis was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan–Meier and multivariate logistic regression analysis.ResultsICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality.ConclusionsEndogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0268-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 97%

The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure

Martín‐Loeches¹,

Muriel-Bombín

Ferrer

et al. 2017

Ann. Intensive Care

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“…In previous study in our group, showed as serum levels of IgG2 (<301 mg/dL) at the time of CAP diagnosis was a mortality predictor for hospitalised patients with CAP and patients with IgG2 levels below this cut-off died sooner 25. Of studies that have investigated the relationship between immunoglobulins and sepsis, Bermejo-Martín et al 26 demonstrated that the combined presence of low levels of IgG1, IgM and IgA in plasma was associated with reduced survival for cases of severe sepsis or septic shock. These results suggest that we should continue the investigation of the target subgroup of patients with CAP, probably using immunoscores with different immunoglobulins to predict prognosis, whereas the use of IVIG as adjunctive treatment during the acute phase of the disease may improve outcome and reduce mortality.…”

Section: Discussionmentioning

confidence: 64%

Serum levels of immunoglobulins and severity of community-acquired pneumonia

et al. 2016

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InstructionThere is evidence of a relationship between severity of infection and inflammatory response of the immune system. The objective is to assess serum levels of immunoglobulins and to establish its relationship with severity of community-acquired pneumonia (CAP) and clinical outcome.MethodsThis was an observational and cross-sectional study in which 3 groups of patients diagnosed with CAP were compared: patients treated in the outpatient setting (n=54), patients requiring in-patient care (hospital ward) (n=173), and patients requiring admission to the intensive care unit (ICU) (n=191).ResultsSerum total IgG (and IgG subclasses IgG1, IgG2, IgG3, IgG4), IgA and IgM were measured at the first clinical visit. Normal cutpoints were defined as the lowest value obtained in controls (≤680, ≤323, ≤154, ≤10, ≤5, ≤30 and ≤50 mg/dL for total IgG, IgG1, IgG2, IgG3, IgG4, IgM and IgA, respectively). Serum immunoglobulin levels decreased in relation to severity of CAP. Low serum levels of total IgG, IgG1 and IgG2 showed a relationship with ICU admission. Low serum level of total IgG was independently associated with ICU admission (OR=2.45, 95% CI 1.4 to 4.2, p=0.002), adjusted by the CURB-65 severity score and comorbidities (chronic respiratory and heart diseases). Low levels of total IgG, IgG1 and IgG2 were significantly associated with 30-day mortality.ConclusionsPatients with severe CAP admitted to the ICU showed lower levels of immunoglobulins than non-ICU patients and this increased mortality.

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“…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.…”

Section: Igsmentioning

confidence: 99%

“…Using cut-offs of 300 mg/dL for IgG1, 35 mg/dL for IgM and 150 mg/dL for IgA, all patients were classified as below or above this cut-off. Then using logistic regression analysis, three immuno-scores were described to be associated with unfavorable outcome: (I) all three IgG1, IgM and IgA below the cutoffs with odds ratio 5.27 for death; (II) both IgG1 and IgM below the cutoffs with odds ratio 3.10 for death; and (III) both IgG1 and IgA below the cutoffs with odds ratio 4.10 for death (9). A total of 171 patients with community-acquired pneumonia (CAP) were enrolled in the second multicenter study.…”

Section: Igs and Sepsis Pathogenesismentioning

confidence: 99%