Neuronal expression of class II major histocompatibility complex (HLA-DR) in 2 cases of Pick disease
R. D. Hollister, M. Xia, M. J. McNamara and B. T. Hyman
Neurology Service, Massachusetts General Hospital, Boston, USA.
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 con-currently.
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 alpha 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 in inflammatory
process.
