We adapted an immunoblotting technique for the immunochemical characterization of cryoglobulins. We first compared the results from 157 samples with results obtained by immunofixation and immunoelectrophoresis and then with clinical observations in 125 cases. Full identification was possible in 98% of the cases by immunoblotting, in 54% by immunofixation, and in 28% by immunoelectrophoresis. Novel microheterogeneity aspects were observed by immunoblotting and immunofixation in 13% and 6% of the cases studied, respectively. Our results confirm the frequency of autoimmune and infectious diseases associated with mixed cryoglobulinemias, whereas a lymphoproliferative syndrome was observed only in cases of cryoglobulinemia with a monoclonal constituent or a microheterogeneity aspect, which was not always revealed by immunofixation or immunoelectrophoresis. The pathophysiological importance and classification of microheterogeneity aspects is not clear. These observations justify using a sensitive and specific method for identifying cryoglobulins, even when present at low concentrations, and call for long-term studies of these patients.

Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death. There are several classical neurological paraneoplastic phenotypes including subacute cerebellar degeneration, limbic encephalitis, encephalomyelitis, and dorsal sensory neuropathy. The patient’s clinical presentations may be suggestive to the treating clinician as to the specific underlying paraneoplastic antibody. Specific antibodies often correlate with the specific underlying tumor type, and malignancy screening is essential in all patients with paraneoplastic neurological disease. Prompt initiation of immunotherapy is essential in the treatment of patients with paraneoplastic neurological disease, often more effective in cell surface antibodies in comparison to intracellular antibodies, as is removal of the underlying tumor.

Autoantibodies, including pathogenic NMDAR antibody, have been demonstrated in the cerebrospinal fluid (CSF) of patients following HSVE. This occurs usually several weeks following initial HSV infection. There is growing evidence of a relationship between HSVE and the subsequent development of NMDAR encephalitis. Possible mechanisms include molecular mimicry or an immune response to direct neuronal damage. Future studies should address if the use of immunotherapy can prevent the development of autoimmunity following HSVE.

The major pelvic ganglia (MPG) contain both parasympathetic and sympathetic postganglionic neurons and provide much of the autonomic innervation to urogenital organs and components of the lower bowel. Whereas many parasympathetic neurons were found to express vasoactive intestinal polypeptide (VIP), no MPG neurons exhibited immunoreactivity for pituitary adenylate cyclase activating polypeptide (PACAP). However, in 3-day cultured MPGs, numerous PACAP-IR cells and nerve fibers were present and transcript levels for PACAP increase As the MPG contains both sympathetic and parasympathetic postganglionic neurons, d significantly. In 3-day cultured MPGs, PACAP immunoreactivity was seen in cells that were also immunoreactive for VIP or neuronal nitric oxide synthase (nNOS), but not tyrosine hydroxylase (TH), indicating that PACAP expression occurred preferentially in MPG parasympathetic postganglionic neurons. Transcript levels for the VPAC2, but not VPAC1 or PAC1 receptor, also increased significantly following 3 days in culture. Transcript levels of activating transcription factor 3 (ATF-3), a marker of cellular injury, were increased 64-fold in 3-day explants and ATF-3-IR nuclei were evident in both TH-IR and nNOS-IR neurons as well as in non-neuronal cells. In sum, these results demonstrate that although only the parasympathetic neurons in explant cultured MPGs increase expression of PACAP, both sympathetic and parasympathetic postganglionic neurons in the cultured MPG whole mount increase expression of ATF-3.