Background:

Influenza infection in transplant patients can be severe but factors predictive of outcome in this setting are unclear. The aim of the study was to determine whether cytokines and specifically the TH₁ vs TH₂ profiles predict clinical outcomes.

Methods:

Solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with acute influenza infection were prospectively enrolled in a multicenter study. Serum specimens were taken at disease onset and one month later. IFNγ as hallmark of TH₁ response, IL4 and IL13 as hallmarks of TH₂ response, and IL2, IL10, IL17a, IL21, IL22, were measured in duplicate using ELISA.

Results:

279 patients with influenza infection (225 SOT and 54 HSCT) had serum collected at diagnosis, of which 231 had follow-up serum. Mean age was 52.4 ± 15.7 years and 59.5% were male. Pneumonia was present in 62 (22.2%), and 28 (10.0%) required ICU admission, 21 (7.5%) required mechanical ventilation; 1-month mortality was 9 (3.2%). At diagnosis, IFNγ was detectable in all patients (median 0.80 pg/mL; IQR 0.62-1.38). IL13 was detectable in all patients (median 4.7 pg/mL; IQR 1.2-32.9). IL4 was detectable in 75/279 (26.9%) patients at a median 0.01 ng/mL (IQR 0.01-0.03). The presence of detectable IL4 at diagnosis was associated with lower incidence of pneumonia (p=0.033). Median IL13 levels increased between disease onset and day 30 in patients without pneumonia, but decreased in patients with pneumonia (p=0.029). Patients admitted to ICU and those requiring mechanical ventilation had a significantly higher baseline IFNγ/IL13 ratio (p=0.009 and 0.022, respectively) suggestive of a proinflammatory and TH₁ skewed response.

The immunoregulatory cytokine, IL10 was detectable in 254 (91.0%); the presence of IL10 at diagnosis was associated with pneumonia (p=0.034); Other cytokines (IL2, IL17, IL21) were detectable in all patients at influenza diagnosis whereas IL22 was present in only 20.8%. None of these were significantly related to clinical outcomes.

Conclusion:

In transplant patients with influenza infection, a pro-inflammatory cytokine profile and a skewing of the immune response towards a TH₁ rather than a TH₂ profile was associated with more severe outcomes. The change in IL10 levels over time is likely a response to severe infection.

CITATION INFORMATION: L'Huillier A., Ferreira V., Hirzel C., Cordero E., Limaye A., Reid G., Englund J., Blumberg E., Humar A., Kumar D. Serum Cytokines as Markers of Influenza Infection Outcomes after Transplantation Am J Transplant. 2017;17 (suppl 3).

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