Inflammation and Immune Suppression following Protein Losing Enteropathy after Fontan Surgery Detected by Cytomics

Abstract

Protein losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after total cavopulmonary connection (TCPC - Fontan circulation) surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study aimed to gain insight into immune phenotype alterations following post- TCPC PLE. Patients and Methods: Patients were studied over a period of up to 5 years after surgery. During routine follow-up, blood samples of TCPC patients without (n = 21) and with manifest PLE (n = 12) and of age-matched healthy children (control, n = 22) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Results: Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, C-reactive protein, serum IL-8 and complement activation). In contrast, the lymphocyte count (NK cells, αβ T cell receptor-positive (TCR+) CD4+ cells, αβ TCR+ CD8+ cells) decreased (60-80%, p < 0.001). The residual T cells had elevated CD25 (IL-2R) and CD69 expression. In PLE patients unique cell populations with CD3+ αβ/γδ TCR- and αβ TCR+ CD4- CD8- double negative phenotype were present in increased frequencies. Conclusions: Our studies show for the first time a dramatically altered leukocyte phenotype, the appearance of double negative cells and the alteration of serum compounds after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases such as systemic lupus erythematosus and celiac disease. We conclude that autoimmune processes may play a role in the etiology and pathophysiology of PLE.

Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone

“…To make our patients group as homogenous (and therefore comparable) as possible, we decided to enroll only patients who underwent correction of ASD or VSD. Surgery for more complex congenital heart disease is associated with substantially longer CPB and cross-clamp times carrying prolonged effect of surgical trauma and CPB on the immune system or is known to be associated with latent immunological abnormalities, e.g., Glenn-Fontan surgery (22)(23)(24).…”

“…Phenotyping of leukocytes was done as detailed elsewhere by the whole blood technique (24,27). About 40 ll EDTA blood was mixed with a cocktail of directly fluorescence dye-conjugated monoclonal antibodies.…”

Age-Related Lymphocyte Subset Changes in the Peripheral Blood of Healthy Children – a Meta-Study

“…Furthermore, there are several indications that are presently not so important for routine diagnostics [31]. Clinical decision making relies on measurable aberrations of the patient's values from the 'normal' [32][33][34]. In children correct decision making heavily depends on the availability of these normal ranges for the respective age groups.…”

Cytomics and nanobioengineering

“…This clinical cell analyses led to the concept of predictive medicine by cytomics which became one important key application for FCM and SBC facilitating individualized therapy (8,9,17).…”

“…It does not only include the methods for high-content analysis of a great number of individual cells in a cellular system but also the concept of analysis of these data. The potential of cytomics is on one hand in single cell analysis in combination with a number of technologies (slide based cytometry (SBC), 9,10), toponomics (11,12), spectral imaging (13), proteomics (14)] and applications [drug discovery (15,16), predictive medicine (7,17), clinical diagnosis, translational medicine, human cytome project (18,19), cardiovascular disease, autoimmune disease (20), oncology (21,22), and microbiology (23)]. On the other hand, it is the (mathematical) top-down approach to systems biology.…”