Selective decrease of serum immunoglobulin G1 as a marker of malignant transformation in colorectal tissue

Abstract

METHODS.Using affinity chromatography, IgG1, IgG2, and total IgG were determined in 36 patients with colorectal carcinoma of different stages and compared 1 Department of Biochemistry, University of with 162 apparently healthy controls. Graz, Graz, Austria. RESULTS.It was found that: 1) the mean values for %IgG1 and %IgG2 of all carci-2 Department of Surgery, University of Graz, noma patients differed significantly from those of the controls; 2) no quantitative Graz, Austria.association was found with tumor stages, and four of five patients with incipient adenocarcinoma within a polyp exhibited the characteristic shift in IgG subclasses; 3 Department of Medical Chemistry, University 3) based on a calculated cutoff, the specificity and sensitivity of %IgG1 to discrimiof Graz, Graz, Austria.nate between controls and carcinoma patients was found to be 88% and 74%, 4 Department of General and Experimental Parespectively; and 4) a quantitative correlation between individual %IgG1 values thology, University of Graz, Graz, Austria.and the probability of correct assignment to carcinoma patients or controls was established.CONCLUSIONS. The significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG represents an indirect, tissue nonspecific, and early marker of malignant proliferation that distinguishes colorectal carcinoma patients from healthy controls with a specificity of 88% and sensitivity of 74%. T he profile of subclasses within total serum immunoglobulin (Ig)G in healthy persons is tightly regulated to 60 -70% IgG1, 20 -30% IgG2, 5 -8% IgG3, and 0.7 -4% IgG4, independently of absolute serum levels of total IgG ranging between 8 and 18 mg/ml. The authors have previously reported a characteristic shift in the composition of IgG subclasses in close association with malignant tumors of various tis- nign diseases did not show comparable findings, nor was such a dysproteinemia observed in other nonmalignant diseases. With cerReceived July 31, 1996; revision received December 3, 1996; accepted December 23, 1996. tain tumors this phenomenon exhibited diagnostic sensitivities and

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

“…Patients afflicted with benign diseases (benign tumours or inflammations) of the tissues so far investigated sometimes showed a similar trend (Kronberger et al, 1994;Schauenstein et al, 1996;Schauenstein et al, 1997), but consistently differed from cancer patients with the same level of significance as did healthy controls. Even though our experience at present does not indicate any significant association of the IgG1/G2 shift with other common diseases, further studies are under way to examine this parameter in selected immunopathological conditions.…”

“…The method was recently described (Schauenstein et al, 1997). In brief, 200 µl of serum was applied to a column (HiTrap, 1 ml, Pharmacia, Uppsala, Sweden) filled with Protein A Sepharose High Performance (Pharmacia, code-no.…”

“…In previous reports it was shown that patients with malignant diseases of various tissue origin exhibit a characteristic and highly significant alteration in the subclass composition of serum IgG, consisting in a reduction in %IgG1 and an increase in %IgG2. This phenomenon has been reported in patients suffering from carcinomas of the female breast (Kronberger et al, 1994), various locations of the female reproductive tract (Schauenstein et al, 1996), and of the colo-rectal region (Schauenstein et al, 1997), and it turned out to exhibit diagnostic sensitivities and specificities comparable to, or -particularly at early tumour stages -far higher than conventional serological tumour markers. Patients with benign tumorous or inflammatory diseases of the respective organs differed in their mean %IgG1 and %IgG2 values from cancer patients with the same high significance as did healthy controls.…”

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.…”