Immunoglobulin G Subclass Responses to Recombinant Em18 in the Follow-Up of Patients with Alveolar Echinococcosis in Different Clinical Stages

Abstract

In this study, we compared the sequential responses of immunoglobulin G (IgG) subclasses to the diagnostic antigen Em18 in sera from patients with alveolar echinococcosis. A total of 225 sera from 36 patients at different clinical stages according to the WHO-PNM staging system were tested. The antibody responses were measured for cohorts with resected and unresected parasitic lesions by enzyme-linked immunosorbent assays (ELISA). Total IgG and, to a lesser extent, IgG4 antibody levels against Em18 correlated with all PNM stages before treatment, whereas levels of IgG2 were low and IgG3 was undetectable. Antibody kinetics, however, depended on the treatment rather than on the PNM stage. For some patients, after curative surgery, IgG1 antibodies dropped below the cutoff earlier than other antibodies, followed by total IgG and IgG4 within 18 months. For some patients with recurrences after surgery, IgG1 and IgG4 reappeared, whereas patients with unresectable lesions but stable disease showed steady declines in the levels of all antibodies, and IgG1 became undetectable in some patients. Additional testing of IgE responses to Em18 showed constantly low levels at all stages and in all cohorts.Alveolar echinococcosis (AE) is caused by the vesicular larval stage of the fox tapeworm Echinococcus multilocularis. The helminth causes dangerous infections characterized by infiltrative growth of the larvae in the livers of natural intermediate hosts such as rodents, and rarely in humans. Metastasis formation may also occur. AE is staged according to the World Health Organization (WHO)-PNM (P, parasitic mass in the liver; N, involvement of neighboring organs; M, metastasis) system (10). Radical resection of parasitic lesions is the preferred treatment (1), but most patients are inoperable at the time of diagnosis (5, 13). In a recent serological study, immunoglobulin G (IgG) antibodies directed against Em18, Em10, and Em2plus antigen compositions showed a close relationship between the clinical status and the treatment of patients with AE (16). In direct comparison, antibodies against Em18 demonstrated the greatest dynamic changeability in all patients, cohorts, and PNM stages, irrespective of the individual treatment. Moreover, Em18 indices had shown the best correlation with the PNM stages prior to treatment. These results prompted us to further investigate the IgG subclass and additionally the IgE response against this diagnostic antigen in patients with either resected or unresectable parasitic lesions. MATERIALS AND METHODSPatients. All patients described in this study were seen at the University Hospital and Medical Center Ulm, Ulm, Germany. A total of 36 patients (225 sera) with a history of hepatic AE and a follow-up period of 1.5 to 6.5 years were included in the study. The patients (age range, 17 to 86 years; mean age, 51.2 years; sex ratio [male to female], 0.57:1) were assigned to different clinical WHO-PNM stages of the disease. All patients had acquired AE in Germany and received benzimidazole therapy. Thirteen p...

Immunochromatographic Test with Recombinant Em18 Antigen for the Follow-Up Study of Alveolar Echinococcosis

“…In cases with curative resections, continuous and dramatic decreases in antibody levels after resection of an alveolar hydatid cyst were observed. These results are consistent with those of previous studies using Em18 and other native E. multilocularis metacestode antigens (1,7,9,12,16,17,18). In cases with unresectable and stable diseases, the kinetics of antibody levels varied in individual patients.…”

“…In a case with a calcified lesion (patient 1), a slow decrease in antibody levels was observed, and the last serum sample became negative by the ELISA but was ICT positive. Because antibody levels in patients are very closely related to the progression of AE (1,7,9,12,16,17,18), the efficacy of chemotherapy using benzimidazole against parasites might influence the variability of antibody responses.…”

“…In contrast, serologic analysis is considered to be useful for monitoring disease activity (4,8,10). Studies by an enzymelinked immunosorbent assay (ELISA) with recombinant E. multilocularis 18-kDa antigen (rEm18) (14) and serum samples from patients in different clinical stages of AE according to the World Health Organization (WHO)-PNM (P, parasitic mass in the liver; N, involvement of neighboring organs; M, metastasis) system (11) have revealed that specific immunoglobulin G (IgG) antibody levels in a patient's serum shows a close relationship between the clinical status and the individual treatment (7,9,17,18). However, the ELISA is time-consuming and requires special materials and equipment, which renders this test unsuitable for direct clinical applications.…”

Recent Advances in the Immunology and Serological Diagnosis of Echinococcosis

“…In order to compare the sequential responses of IgG subclasses to Em18 in sera from patients with AE, a total of 225 sera from 36 patients at different clinical stages according to the WHO-PNM staging system (Pawlowski et al, 2001) were tested. The levels of serum IgG and IgG4 against Em18 correlated with the PNM stages compared with sera from patients receiving no treatment (Tappe et al, 2010).…”

Comparisons of Serum Total IgE, IgG, and IgG1 Levels in Patients with and without Echinococcosis-Induced Anaphylactic Shock

“…4 To clarify the pathogenesis of echinococcosis-induced anaphylactic shock, we analyzed the serum levels of total IgE, IgG, and IgG1 both during and after anaphylactic shock and compared these to echinococcosis patients without shock after cyst rupture.…”