Elevation of soluble major histocompatibility complex class I related chain A protein in malignant and infectious diseases in Chinese patients

Abstract

Background: Elevation of soluble major histocompatibility complex class I chain-related gene A (sMICA) products in serum has been linked to tissue/organ transplantation, autoimmune diseases and some malignant disorders. Cells infected by microbiological pathogens may release sMICA, whereas less is known whether and to what extent serum sMICA levels may change in infectious diseases.

Methods: The present study determined serum sMICA levels by enzyme-linked immunosorbent assay (ELISA) in a southern China population, including patients (n = 1041) suffering from several types of malignant and infectious diseases and healthy controls (n = 141).

Results: Relative to controls, serum sMICA elevation was significant in patients of hepatic cancer, and was approaching statistical significance in patients with lung, gastric and nasopharyngeal cancers. sMICA elevation was also associated with some bacterial (Enterobacteriaceae, Mycobacterium tuberculosis, non-fermenting Gram-negative bacteria and Gram-positive cocci), viral (hepatitis B and C) and the Microspironema pallidum infections.

Conclusion: Serum sMICA levels may be informative for the diagnosis of some malignant and infectious diseases. The results also indicate that microbiological infections should be considered as a potential confounding clinical condition causing serum sMICA elevation while using this test to evaluate the status of other disorders, such as cancers, host-graft response and autoimmune diseases.

Figure 1

Example of the standard curve for serum soluble Major histocompatibility Complex class I related chain A (sMICA) generated by Sandwich ELISA in a typical assay. Concentrations of the recombinant MICA*008 are plotted against the readings of optic absorbance. A liner relationship exists between the values of optic absorbance and concentrations of the MICA*008. The values are averaged from duplicated loadings at each concentration.

Figure 2

Dot graph showing the distribution and means (blue bars) of serum sMICA concentration (pg/ml) among cancer patients (red) relative to healthy control (green) groups. The liver cancer group shows the highest mean, with the levels of sMICA remarkably elevated among some individuals. Each dot represents an individual case, referring to Table 2 for case numbers in each group and statistics.

Figure 3

Receiver operating characteristic (ROC) curves illustrating the diagnostic impact of serum sMICA levels in different malignant tumors, as determined by the values of area under the ROC curve (AUC). The data indicate that test has the highest diagnostic value (AUC = 0.834) among patients of hepatic cancer relative to other malignant tumors.

Figure 4

Dot graph plots the distribution and means (blue bars) of serum sMICA concentration (pg/ml) among patients suffering various microbial infections (red), relative to healthy controls (green). Each dot represents an individual case. Please refer to Table 4 for sample sizes and statistical analysis information.

Figure 5

Receiver operating characteristic (ROC) curves illustrating the diagnostic impact of serum sMICA levels in different infectious diseases, with the values of area under the ROC curve (AUC) labeled for each type of infections. The data indicate that test has an intermediate diagnostic impact (AUC > 0.7) among patients with infections by hepatitis B (A) and C (B) viruses; Microspironema pallidum (C), bacillus tuberculosis (D) and Gram-negative bacterium (F). In contrast, the diagnostic value is low in the patient group with infections including herpes simplex virus, Coxsackie virus, Epstein-Barr virus, cytomegalovirus, hepatitis A virus and hepatitis E virus (E).