our study had such symptoms, but it should be noted that distemper may be subclinical in as many as 75% of affected animals [I]. Dr Karis also raises questions concerning exposure to pets at various ages and the duration of the “latent period” before MS becomes manifest. W e did not analyze for exposure to pets in each five-year period of life, but directed our studies to the five and ten years prior to onset of symptoms. In this study, significantly greater exposure to small indoor dogs was found in the five-year but not the ten-year interval prior to onset of symptoms, whereas in our previous study, both intervals were significant for house pet exposure. If the animal-MS relationship bears the test of time, it may be that the “latent period” before onset of symptoms in some patients will be found to be shorter than is generally appreciated.

Refemzces 1. Appel MJG, Gillespie JH: Canine Distemper Virus. Vienna, Springer-Verlag, 1972, p 75 2. Cook SD, Dowling PC: A possible association between house pets and multiple sclerosis. Lancet 1:980-982, 1977 3. Cook SD, Natelson BH, Levin BE, et al: Further evidence of a possible association between house dogs and multiple sclerosis. Ann Neurol 3:141-143, 1978 4. Kurland L, Brian D: Multiple sclerosis and canine pets (editorial). Ann Neurol 3:97-100, 1978 5 . Schoenberg BS: Neuroepidemiology, incidents, incidence, and coincidence. Arch Neurol 34:261-265, 1977

production and effector cell proliferation can be dissociated, in that MIF production can occur under conditions in which dividing cells have been either poisoned or previously eliminated. Finally, Rocklin et a1 [7] have reported that while sensitized T- and B-cells both respond to streptokinase-streptodornase varidase (SKSD), purified protein derivative (PPD), and Candzdu antigen with MIF production, B-cells fail to proliferate. Thus while Williams et a1 [8] have data which confirm that MIF production can be dissociated from lymphocyte transformation, their data do not support the contention that our own observations cannot be confirmed. Our claim has received additional support from a rigorous double-blind study commissioned by the Hereditary Disease Foundation and administered by the Human Neurospecimen Bank of America (Wadsworth Veterans Administration Hospital, Los Angeles, CA) and D r Ron Konopka of the Division of Biology, California Institute of Technology [2].

References

Immunological Studies in Huntington’s Disease

1. Barkley DS, Hardiwidjaja S, Menkes JH: Huntington’s disease: delayed hypersensitivity in v i m to human central nervous system antigens. Science 195:314-316, 1977 2. Barkley DS, Hardiwidjaja SI, Tourtellotte WW, et al: Cellular immune responses in Huntington’s disease. Specificity of brain antigenicity detected with Huntington’s disease lymphocytes. Neurology (Minneap) 28:32-35, 1978 3. Bloom BR, Gaffney J, Jiminez L: Dissociation of M.I.F. production and cell proliferation. J Immunol 109:1395-1 398, 1972 4. Chaparas SD, Thor DE, Godfrey HP, et al: Tuberculin-active carbohydrate that induces inhibition of macrophage migration but not lymphocyte transformation. Science 170:637-639,

David S. Barkley, PhD, and Steven I. Hardiwidjaja, M D

1970 5 . Philp, JR, Johnson JE 111, Spencer JC: Amplification of mi-

Williams et a1 [ 8 ]in a letter to Annals of Neurology reported an inability to distinguish Huntington’s disease (HD) from control brain tissue through the transformation of HD lymphocytes. They concluded that “although lymphocyte transformation was used instead of migration inhibition technique, our results d o not confirm the previous claims of Barkley et al” [l]. We have also studied lymphocyte transformation and confirm that it is, in our hands, unable to distinguish HD from control brain tissue (unpublished results). However, we do not believe that such results cast doubt on the validity of findings obtained with the migration inhibition factor (MIF) assay. The cellular immune response is a complex of events with a variety of in vitro correlates, few of which are universally present in specific instances. For example, Chaparas et a1 [4] have demonstrated that a carbohydrate fraction of tuberculin is skin reactive in tuberculin-sensitive guinea pigs and causes MIF production in an in vitro system but does not induce lymphocyte transformation. Bloom et a1 [ 3 ] ,Rocklin [6], and Philp et a1 [ 5 ] have shown that MIF

gratory inhibition factor production during the first 48 hours of exposure to antigen. Infect Immunol 8:781-786, 1973 6. Rocklin RE: Production of migration inhibitory factor by nondividing lymphocytes. J Immunol 110:674-678, 1973 7. Rocklin RE, MacDermott RP, Chess L, et al: Studies o n mediator production by highly purified human T and B lymphocytes. J Exp Med 140:1303-1316, 1974 8 Williams RC, Jr, Lewis M, Montano J, et al: Immunological studies related to brain antigens in Huntington’s disease. Ann Neurol 3:185-186, 1978

From the Departments of Pathology and Neurology, University of California Center for the Health Sciences, Los Angeles, CA 90024.

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