Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis

Abstract

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).

Autoimmune basal ganglia encephalitis associated with anti-recoverin antibodies: A case report

“…Next, we discuss the relationship between anti-recoverin Abs and CNS involvement in autoimmune basal ganglia encephalitis. For instance, patients with ocular toxoplasmosis also have progressive retinal or CNS symptoms due to anti-recoverin Abs [ 7 ]. Furthermore, recoverin shares epitopes with CNS endogenous antigens; therefore, anti-recoverin Abs that reach the CNS via the blood-brain barrier could show cross-reactivity within the CNS [ 7 ].…”

“…For instance, patients with ocular toxoplasmosis also have progressive retinal or CNS symptoms due to anti-recoverin Abs [ 7 ]. Furthermore, recoverin shares epitopes with CNS endogenous antigens; therefore, anti-recoverin Abs that reach the CNS via the blood-brain barrier could show cross-reactivity within the CNS [ 7 ]. In the CNS, neuron-specific Ca 2+ -binding protein neuronal cells in the caudate-putamen mainly express hippocalcin [ 8 ], which shows 51% sequence similarity with recoverin [ 9 ].…”

“…Anti-recoverin Abs are often detected in the serum after infections such as toxoplasmosis, and one of the initial symptoms of our patient was a fever, which differentiated post-infectious immune-mediated basal ganglia encephalitis. One of the mechanisms of entry of anti-recoverin Abs into the CNS was a direct route of entry via the bloodstream, which was influenced by systemic inflammation [ 7 ]. However, the patient had no prior infection.…”