March 1997

Neuronal Expression of Class II Major Histocompatibility Complex (HLA-DR) in 2 Cases of Pick Disease

Author Affiliations

From the Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

Arch Neurol. 1997;54(3):243-248. doi:10.1001/archneur.1997.00550150011008

Background:  Pick disease is a progressive form of dementia characterized by personality changes, speech disturbances, inattentiveness, and occasionally extrapyramidal phenomena. Although several variants have been recognized, the pathological profile of Pick disease includes focal frontotemporal atrophy, neuronal loss, astrocytosis, Pick bodies, and Pick cells. To date, little is known about the etiology of Pick disease.

Objective:  To evaluate the possibility of inflammatory processes occurring in Pick disease pathophysiology.

Design:  Immunohistochemistry for HLA-DR and related molecules was performed in brain tissue from individuals with Pick disease, Alzheimer disease, and diffuse Lewy body disease, as well as from neurologically normal controls.

Results:  We report the unusual expression of the class II major histocompatibility complex protein Ia (HLA-DR) on neurons in 2 cases of Pick disease. In addition, both cases exhibited a dramatic microglial response. Neuronal HLA-DR immunostaining was not observed in 12 other cases of Pick disease or cases of Alzheimer disease, cases of diffuse Lewy body disease, or in control cases run concurrently. In addition, the pattern of HLA-DR staining observed in Pick disease was confirmed with another monoclonal antibody to HLA-DR. Frequent in vitro inducers of HLA-DR expression and enhanced class I major histocompatibility expression, interferon gamma, and tumor necrosis factor α were not detected. CD4-positive T lymphocytes were also not present and class I major histocompatibility complex expression was not detected on neurons or glia from brain tissue with Pick disease.

Conclusions:  These results are the first to demonstrate class II major histocompatibility complex expression on neurons. Based on these preliminary results, we suggest that some cases of Pick disease may be complicated by or involve an inflammatory process.