Schistosoma antigens: A future clinical magic bullet for autoimmune diseases?

Abstract

Autoimmune diseases are characterized by dysregulated immunity against self-antigens. Current treatment of autoimmune diseases largely relies on suppressing host immunity to prevent excessive inflammation. Other immunotherapy options, such as cytokine or cell-targeted therapies, have also been used. However, most patients do not benefit from these therapies as recurrence of the disease usually occurs. Therefore, more effort is needed to find alternative immune therapeutics. Schistosoma infection has been a significant public health problem in most developing countries. Schistosoma parasites produce eggs that continuously secrete soluble egg antigen (SEA), which is a known modulator of host immune responses by enhancing Th2 immunity and alleviating outcomes of Th1 and Th17 responses. Recently, SEA has shown promise in treating autoimmune disorders due to their substantial immune-regulatory effects. Despite this interest, how these antigens modulate human immunity demonstrates only limited pieces of evidence, and whether there is potential for Schistosoma antigens in other diseases in the future remains an unsolved question. This review discusses how SEA modulates human immune responses and its potential for development as a novel immunotherapeutic for autoimmune diseases. We also discuss the immune modulatory effects of other non-SEA schistosome antigens at different stages of the parasite's life cycle.

Keywords: Autoimmune diseases; Immunotherapy; Schistosome; Schistosomiasis; Soluble egg antigen.

Figure 1

Immune responses induced by SEA. SEA induces M2 differentiation of macrophages and prevents toll-like receptor-dependent activation of dendritic cells, which is correlated with reduced production of inflammatory cytokines. Dendritic cells also induce the differentiation of CD4⁺ T cells into the Th2 subset through a CD40-dependent mechanism. SEA can also activate Th2 CD4⁺ T cells and regulatory B cells. Regulatory B cells, once activated, secrete IgE and further stimulate basophil production of IL-4 and IL-13, which then induce Th2 CD4⁺ T cells. Th2 CD4⁺ T cells can release various Th2 cytokines such as IL-4, IL-5, IL-10, and IL-13, shifting the overall immunity into a Th2-dominant response.