Jakob Hauge Mikkelsen

Various subspecies of the unicellular parasite Trypanosoma brucei cause sleeping sickness, a neglected tropical disease affecting millions of individuals and domestic animals. Immune evasion mechanisms play a pivotal role in parasite survival within the host and enable the parasite to establish a chronic infection. In particular, the rapid switching of variant surface glycoproteins covering a large proportion of the parasite’s surface enables the parasite to avoid clearance by the adaptive immune system of the host. In this article, we present the crystal structure and discover an immune-evasive function of the extracellular region of the T. brucei invariant surface gp75 (ISG75). Structural analysis determined that the ISG75 ectodomain is organized as a globular head domain and a long slender coiled-coil domain. Subsequent ligand screening and binding analysis determined that the head domain of ISG75 confers interaction with the Fc region of all subclasses of human IgG. Importantly, the ISG75–IgG interaction strongly inhibits both activation of the classical complement pathway and Ab-dependent cellular phagocytosis by competing with C1q and host cell FcγR CD32. Our data reveal a novel immune evasion mechanism of T. brucei, with ISG75 able to inactivate the activities of Abs recognizing the parasite surface proteins.

Anti‐muscarinic type 3 receptor autoantibodies (M3R) and anti‐SSA antibodies are both related to salivary secretion. The presence of M3R antibodies in Sjögren's syndrome is previously demonstrated; nevertheless, the relationship between the anti‐SSA antibodies and M3R fragment antibodies, namely the N terminal, first, second, and third extracellular loops, remains to be elucidated. In this study, we analyzed the antibodies against the M3R epitopes in healthy controls and anti‐SSA antibody‐positive connective tissue disease patients through ELISA method. Antibodies against the first, second, and third extracellular loop (M3R 211–230 ) were not increased in anti‐SSA positive patients compared to healthy controls. Indeed, antibodies against the N terminal (M3R 1–33 ) were found to be high in healthy controls. High levels of M3R 1–33 in healthy controls are a novel original finding; further research is needed for the clinical significance. There is no significant difference between SSA‐positive patients and healthy controls in terms of autoantibodies against the remainder of the linear M3R fragments.