The IgG1/G2 subclass shift – a sensitive, tissue non-specific marker for malignancy. Diagnostic performance with squamous cell carcinoma of the head and neck

Abstract

Summary A significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG has been previously reported as a highly sensitive marker for detecting early stages of carcinomas of various localizations. Here we investigated the question as to whether this phenomenon is also observed in sera of patients with squamous cell carcinoma of the head-neck region (SCC-HN), and to evaluate its diagnostic performance in the post-operative monitoring. Using quantitative affinity chromatography, serum concentrations of IgG1, IgG2 and total IgG were determined in 81 patients with different stages of primary and untreated SCC-HN, in 51 SCC-HN patients in post-therapeutical follow up, and in 33 patients with organ matched benign diseases. The data were compared with a total of 174 healthy controls. It was found that (i) 105 SCC-HN patients exhibited a mean value of 56.0 ± 0.7% IgG1, which likewise differed from healthy controls (63.2 ± 0.5) and benign diseases (61.5 ± 1.0) with P < 0.0005, (ii) sensitivities and specificities for discriminating primary malignancies from healthy controls were 70 and 74% respectively, and from benign diseases 65 and 76%, (iii) highest sensitivities and specificities were observed with posttherapeutic cases suffering from tumour recurrence (88% and 75%) or patients with distant metastases (87% and 86%), (iv) apparently tumour-free post-therapeutic patients showed a mean %IgG1 not different from the normal value. The decrease in %IgG1 accompanied by increased %IgG2 is an efficient, sensitive and early marker of SCC-HN, which appears particularly useful for the post-therapeutic monitoring.

IgG2 response and low IgG titre specific to Helicobacter pylori CagA as serological markers for gastric cancer

“…Possible explanations for this shift are that CagA could preferentially evoke T-helper 1 (Th1) responses, as has been observed in peptic ulcer patients (D'Elios et al, 1997), or that the IgG2 antibody response increases with age (Lottenbach et al, 1999). Alternatively, the shift might be related to the carcinogenesis process C. F. de la Cruz-Herrera and others itself, as patients with cancer usually show a characteristic and significant alteration in the pattern of serum IgG subclasses, with an increase in IgG2 and a reduction in IgG1 (Schauenstein et al, 1997;Anderhuber et al, 1999). Analogous results have been observed in rodent models (Haddada et al, 1984;Weblacher et al, 1993).…”

“…To date, there are only two reports on the IgG subclass response to CagA in children and young adults with benign diseases; CagA is predominantly recognized by IgG1, followed by IgG3 and then IgG2, and it fails to stimulate an IgG4 response (Dzierzanowska-Fangrat et al, 2003;Du et al, 2006). As in many infections, the IgG subclass response to infecting pathogens has been associated with the severity of clinical symptoms, and because patients with malignant diseases exhibit a significant alteration in the composition of serum IgG subclasses (Hussain et al, 1995;Lagacé et al, 1995;Schauenstein et al, 1997;Anderhuber et al, 1999), the present work aimed to evaluate the total IgG antibody response and that of the subclasses IgG1 and IgG2 against H. pylori antigens in patients with GC, intestinal metaplasia (IM) or NAG.…”

The tumor-associated shift in immunoglobulin G1/G2 is expressed at the messenger RNA level of peripheral blood B lymphocytes in patients with gynecologic malignancies

“…1 This phenomenon has been observed in patients with carcinomas of the mammary gland, 2,3 the female reproductive tract, 4 and the colorectal region, 5 and very recently with squamous cell carcinomas of the head and neck region. 6 Organmatched benign diseases and other nonmalignant diseases investigated so far have not shown comparable changes in the IgG subclass pattern. With certain tumor locations, this IgG subclass shift was found to exhibit diagnostic sensitivities and specificities that were comparable or, especially at early tumor stages, by far superior to conventional serologic tumor markers.…”

“…6 The aim of the current study was to investigate the mechanism(s) responsible for the tumor-associated shift in IgG subclass serum levels. In particular, the question was addressed as to whether this phenomenon was detectable at the level of the IgG-producing B lymphocytes.…”

Selective reduction of anti‐Helicobacter pylori IgG subclass antibody in gastric carcinoma

“…It has also been suggested that the malignant process itself could interfere with the biosynthesis of IgG subclasses at the B-lymphocyte level. 22 An IgG1/G2 subclass shift has been reported in subjects with squamous cell carcinoma of the head and neck, breast cancer, colorectal cancer and with carcinomas of various locations of the female reproductive tract. [22][23][24] This effect of malignant tumors may be mediated by modulation of the secretion of certain cytokines and/or their soluble receptors.…”