Concomitant occurence of multiple autoantibodies against human cytochromes P450

Int Immunopharmacol. 2021 Nov:100:108087. doi: 10.1016/j.intimp.2021.108087. Epub 2021 Aug 28.

Abstract

Cytochromes P450 (CYPs) are a large superfamily of heme-containing enzymes that are essential for the metabolism of a variety of endogenous and xenobiotic compounds. The role and the possible diagnostic or prognostic value of the occurrence of anti-CYP autoantibodies (aAbs) in cancer patients are essentially unclear. Recently we reported the monitoring of aAbs against CYP4Z1 and CYP19A1 in breast cancer patients and healthy controls. In the present study, we extended this investigation by screening the sera of 47 lung cancer patients (17 female and 30 male; age range 49-84) and 119 healthy controls (60 female and 59 male; age range 21-72) for the presence of aAbs directed against CYP2D6, CYP4Z1, or CYP17A1, respectively. Determination of anti-CYP aAb levels was done using our previously established ELISA method. Most sera gave low signals while a small fraction showed stronger responses; however, there were no statistically significant differences between the different test groups. Also, there was no significant difference in aAb signals between the various subtypes of lung cancer. Unexpectedly, sera from two female lung cancer patients (age 67 (adenocarcinoma) and 70 (small cell carcinoma)) and from four healthy controls (one female and three male; age range 34-48) showed significantly elevated signals for more than one of the three CYPs tested. These findings corroborate earlier reports that anti-CYP aAbs occur with low frequency in the general population and, moreover, suggest that the simultaneous presence of multiple aAbs targeting different CYPs should be taken into consideration when evaluating anti-CYP aAbs as biomarkers.

Keywords: Autoantibodies; Biomarker; Cytochrome P450; Lung cancer.

MeSH terms

  • Adenocarcinoma of Lung / blood
  • Adenocarcinoma of Lung / enzymology
  • Adenocarcinoma of Lung / immunology*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Cytochrome P-450 CYP2D6 / immunology
  • Cytochrome P-450 Enzyme System / immunology*
  • Cytochrome P450 Family 4 / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Small Cell Lung Carcinoma / blood
  • Small Cell Lung Carcinoma / enzymology
  • Small Cell Lung Carcinoma / immunology*
  • Small Cell Lung Carcinoma / pathology
  • Steroid 17-alpha-Hydroxylase / immunology
  • Up-Regulation
  • Young Adult

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • Cytochrome P-450 Enzyme System
  • CYP4Z1 protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P450 Family 4
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase