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

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).

Immune mediated neurologic dysfunction as a paraneoplastic syndrome in renal cell carcinoma.

OBJECTIVE: To describe a case of cerebellar ataxia associated with renal cell carcinoma. CASE REPORT: A 53-year-old Caucasian male with a history of Schizophrenia presented with generalized weakness, nausea, vomiting, severe weight loss, and progressively worsening gait difficulty associated with multiple falls. Physical examination revealed profound ataxia with inability to ambulate despite normal strength. The patient also appeared cachectic. A contrast-enhanced CT of the abdomen/pelvis showed a 10.4 x 8.3 cm(2) left renal mass. Histopathology of the tissue revealed morphology consistent with renal cell carcinoma. Paraneoplastic antibodies including anti-Hu, anti-Ma, anti-Ri, and anti-Yo were negative, however, biotinylated serum analysis was positive for hippocampal and cerebellar Purkinje cells. DISCUSSION: The pathogenesis of paraneoplastic neurological syndromes is believed to be associated with antibody and T-cell mediated response to antigens shared between the tumor and neural tissue. Though serum from this patient was negative for well-characterized antibodies, further testing revealed the presence of proteins binding to the hippocampal region of the midbrain and the cerebellum, and to components of the extracellular matrix of the tumor which may suggest partially characterized or as yet uncharacterized antibodies directed against renal cell tumor tissue and the nervous system. This possibility is supported by the observed symptom resolution upon tumor resection. The described case introduces a possible association between an antibody, which may be specific to paraneoplastic neurological syndromes, and renal cell carcinoma.