Neural system antigens are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia.

BACKGROUND: Endemic pemphigus foliaceus (EPF), is also known as "fogo selvagem" or "wild fire," reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). METHODS: We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens. RESULTS: We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p<0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy. CONCLUSIONS: Our findings may explain for the first time the "pose of pemphigus," representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the "burning sensation" encountered in EPF disease.

Antibody-mediated lysis of the bovine subcommissural organ maintained in culture.

The subcommissural organ (SCO) is a brain gland that secretes glycoproteins into the cerebrospinal fluid (CSF). It is an ancient and conserved secretory structure of the brain, developing very early in ontogeny. However, the function of the SCO is unknown. The secretory cells of the SCO are arranged into a single or double, irregularly shaped layer located at the interface of the CSF and nervous tissue. This has prevented its selective surgical destruction. The present investigation was designed to destroy the secretory cells of 30-day-old explants of bovine SCO by use of an immunological approach. A membrane preparation enriched with plasma membrane of the secretory cells of the bovine SCO was obtained. This preparation was further processed to separate the structural proteins. A similar procedure was applied to obtain a fraction of integral proteins of the plasma membrane of a nonsecretory ciliated ependyma. Antisera were prepared against both preparations of integral proteins. The antiserum against the fraction obtained from the SCO cells immunostained the plasma membrane of the bovine SCO cells and in immunoblot it reacted with several proteins of the membrane preparation from SCO cells. When added to the culture medium this antibody bound to the apical plasma membrane of the secretory ependyma of the bovine SCO kept in culture; it caused the lysis of these cells when used together with complement. None of these properties were displayed by the antiserum raised against the integral proteins of the plasma membrane of the ciliated ependyma. This antiserum, however, immunostained the bovine ciliated ependyma neighboring the SCO. These results indicate that immunological surgery of the SCO in living animals may be possible to achieve.

Immune complexes in the choroid plexus in liver cirrhosis.

A histopathologic and immunofluorescence study of the choroid plexus was performed in 12 cases of liver cirrhosis (cirrhosis group) and in 20 patients who died of diseases with no evidence of liver or brain involvement, and in which renal disease and alcoholism were also excluded (control group). IgA, IgG, IgM, C3, and C1q were investigated by direct immunofluorescence technique. Positive immunofluorescence in the choroid plexus was found in 83.33% of the cirrhosis group. IgA and IgG were the immunoglobulins more frequently found. C3 was also commonly found. Histologic examination of the choroid plexus showed changes in 66.67% of the cirrhosis group characterized, mainly, by subepithelial deposition of a homogeneous, acidophilic, and periodic acid-Schiff-positive substance, with thickening of the epithelial basement membrane. In the control group, the immunofluorescence in the choroid plexus was negative in all cases and only two cases (10%) presented histopathologic changes of the choroid plexus with a pattern similar to that of the cirrhosis group.

Histopathological and immunofluorescence study of the choroid plexus in hepatosplenic schistosomiasis mansoni.

A histopathological and immunofluorescence (IMF) study of the choroid plexus was performed in 8 cases of hepatosplenic schistosomiasis mansoni and in 20 cases which had resulted in death with no evidence of liver or brain involvement by schistosomiasis or other disease process, and in which renal disease and arterial hypertension were also excluded (control group). IgA, IgG, IgM, C3, and C1q were investigated. Positive IMF in the choroid plexus was found in 75% of the schistosomiasis group. IgA and IgG were the immunoglobulins (Ig) most frequently found. C3 was also commonplace. Histologic examination of the choroid plexus showed changes in 87.5% of the schistosomiasis group. The most frequently found change was characterized by focal, linear, occasionally nodular, subepithelial deposition of a homogeneous, acidophilic, and PAS positive substance, apparently in relation to the epithelial basement membrane, with thickening of this structure. In the control group, the IMF in the choroid plexus was negative in all cases, and only 2 cases (10%) presented histopathological changes of the choroid plexus with a pattern similar to that of the schistosomiasis group. The demonstration of the deposition of Ig and fractions of the complement system, and of histological changes in the choroid plexus in a liver disease which is known to exhibit circulating immune complexes and glomerulopathy with deposition of Ig and fractions of the complement system suggests an etiopathogenetic relationship between both findings.