Proteomic profile of circulating immune complexes in chronic Chagas disease

Abstract

Summary 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.

Immune complexes in chronic Chagas disease patients are formed by exovesicles from Trypanosoma cruzi carrying the conserved MASP N-terminal region

“…identified 39 T. cruzi antigens in circulating ICs including surface antigens such as trans -sialidases, gp63 and MASPs in samples from patients with Chagas disease. Similarly to the findings of our study, the same authors also showed the association of two hypothetical proteins with ICs from patients suffering mega colon30, revealing an association between ICs composition and chronic Chagas disease manifestations.…”

“…6). Recently, Ohyama et al 30. identified 39 T. cruzi antigens in circulating ICs including surface antigens such as trans -sialidases, gp63 and MASPs in samples from patients with Chagas disease.…”

“…29. One recently published proteome of circulating ICs in chronic Chagas disease patients has shed light onto the composition of these ICs which appear to be formed by proteins belonging to T. cruzi surface families involved in processes of adhesion or invasion of host cells among others30.…”

Role of Proteomics in the Study of Trypanosoma cruzi Biology

“…Therefore, the identification of foreign constituents or autoantigens within ICs might provide new insights into the immunopathology of infectious diseases. Ohyama and coworkers [68] studied the immune complexome of plasma samples obtained from T. cruzi-infected patients. Then, 20 seropositive plasma samples, including cardiac and/or megacolon chronic patients (n = 11) and asymptomatic patients (n = 9), were analyzed together with 10 seronegative healthy people to investigate the antigens linked to circulating ICs.…”

Proteomic approach to profiling immune complex antigens in cerebrospinal fluid samples from patients with central nervous system autoimmune diseases

“…In order to comprehensively identify and profile constituent antigens in ICs, we developed a proteomic strategy, designated immune complexome analysis, in which ICs are separated from whole serum and then subjected to direct tryptic digestion and nano-liquid chromatography-tandem mass spectrometry [22]. We have successfully used this method to identify disease-specific IC antigens in the sera of patients with autoimmune diseases [22][23][24][25], infectious diseases [26,27] and cancer [28]. Therefore, profiling of IC-associated antigens in CSF by immune complexome analysis might provide insights into pathophysiology of CNS autoimmune diseases and other neurological diseases, and such analyses could form the basis for novel diagnostic and treatment strategies for these diseases.…”