CD4 + CD25 + CD127 high cells as a negative predictor of multiple organ failure in acute pancreatitis

Abstract

Background: It has been suggested that severity of the immune response induced by immune cells is associated with morbidity and mortality from acute pancreatitis. The authors investigated and evaluated the relationship between distinct peripheral lymphocyte subsets at admission and clinical outcome prior to hospital discharge so as to find a predictor to the prognosis of acute pancreatitis in lymphocyte profile.

Methods: Lymphocyte subsets in admission peripheral venous blood were tested through flow cytometry on 48 patients with acute pancreatitis. Clinical data was recorded as well. The primary observational outcomes were multiple organ failure (MOF) and infection.

Results: There was a significant difference in natural killer cells between two subgroups sorted by the presence or absence of infection (25.5 ± 4.47 [95% CI 14.4, 36.6] vs 14.8 ± 7.62 [95% CI 12.5,1 7.1] p = 0.021). Patients who developed MOF had lower CD4 + CD25 + CD127^high (4.49 ± 1.5 (MOF) [95% CI 3.83, 5.16] vs 6.57 ± 2.65 (non-MOF) [95% CI 5.5, 7.64] p = 0.002) and higher CD127low/high cell counts (1.35 ± 0.66 [95% CI 1.06, 1.65] vs 0.97 ± 0.44 [95% CI 0.79, 1.15] p = 0.02). MOF patients were significantly older (55 ± 14.58 [95% CI 48.49,61.42] vs 46 ± 15.59 [95% CI 39.39,51.99] p = 0.04), and had higher Acute Physiology and Chronic Health Evaluation IIscores (7 ± 3.66 [95% CI 5.5,7.64] vs 4 ± 2.89 [95% CI 2.45,4.78] p = 0.001) and C reactive protein (100.53 ± 94.38 [95% CI 58.69,142.48] vs 50.8 ± 59.2 [95% CI 26.88,74.71] p = 0.04). In a multivariate regression model, only CD4 + CD25 + CD127^high cell was a significant predictor of non-MOF. For the detection of non-MOF, CD4 + CD25 + CD127^high cell generated a receiver operating characteristic (ROC) curve with an area under the curve of 0.74.

Conclusion: CD4 + CD25 + CD127^high cell at early phase of acute pancreatitis yields good specificity in detecting non-MOF at a suggested cutoff value 6.41%. Patients with fewer natural killer cells may be at risk in developing secondary infection.

Keywords: Acute pancreatitis; CD4 + CD25 + CD127high cell; Multiple organ failure; Natural killer cells; Prognosis; Regulatory T cell.

Fig. 1

A 28-year-old man with acute necrotizing pancreatitis complicated by infected pancreatic necrosis requiring multiple percutaneous catheter drainage (red arrow in A and B). There is a large heterogeneous area of necrosis in the pancreatic and peri-pancreatic area with impacted gas bubbles (yellow ring in B)

Fig. 2

Gating strategy of peripheral lymphocyte population (a) Gating strategy for CD4+ T cell subdivided into CD4 + CD25 + CD127^low and CD4 + CD25 + CD127^high subpopulation. B indicate lymphocyte divided from leukocyte based on forward scatter and side scatter, K indicate CD4+ T cells, G2 indicate CD4 + CD25 + CD127^high cells and G4 CD4 + CD25 + CD127^low cells. b Gating strategy for lymphocyte subdivided into T Helper cells, cytotoxic T cells and NK cells subpopulation. H indicate CD3+ T cells, F2 indicate CD3 + CD4+ T cells and J2 CD3 + CD8+ T cells, E1 indicate CD3-CD16 + CD56+ cells which were divided from CD3- T cells. c Gating strategy for B cells. C indicate lymphocyte divided from leukocyte according to CD45 and side scatter. D2 indicate CD19 + CD20 + CD45+ cells

Fig. 3

mean NK cells percentage of lymphocytes at admission in infection group vs non- infection

Fig. 4

ROC curve of CD4 + CD25 + CD127^high cell in predicting non-MOF developing in the progress of acute pancreatitis

Fig. 5

ROC curve of APACHEIIversus CRP in predicting MOF developing in the progress of acute pancreatitis