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Proteomic profile of circulating immune complexes in chronic Chagas disease
K Ohyama1,2, N T Huy3, H Yoshimi1
1Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Insights
Immune complexome analysis identified Trypanosoma cruzi and human autoantigens in Chagas disease patients. Specific antigens distinguished between indeterminate and determinate forms, revealing differences in immune status.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Immune complexes (ICs) are key indicators of humoral immune responses.
- Identifying antigens in ICs can illuminate infectious disease pathology.
- Chagas disease, caused by Trypanosoma cruzi, presents complex clinical manifestations.
Purpose of the Study:
- To characterize antigens within circulating ICs in Chagas disease patients.
- To differentiate antigen profiles between indeterminate and determinate forms of chronic Chagas disease.
- To explore the utility of immune complexome analysis in understanding disease progression.
Main Methods:
- Immune complexome analysis was performed on plasma samples.
- Twenty seropositive Chagas disease patients (cardiac/megacolon determinate and indeterminate) were analyzed.
- Ten seronegative individuals served as controls.
Main Results:
- 39 T. cruzi antigens and 114 human autoantigens were identified in Chagas patients.
- Specific T. cruzi (GP63, glucose-6-isomerase) and human autoantigens were prevalent in over 50% of patients.
- T. cruzi trans-sialidase and human complement factor H-related protein 2 were more frequent in indeterminate cases.
Conclusions:
- Immune complexome analysis effectively identifies pathogen and host antigens in Chagas disease.
- Distinct antigen profiles correlate with different clinical forms of chronic Chagas disease.
- This approach offers insights into the varying immune status associated with disease progression.
Abstract:
Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease.
