To further demonstrate an immune component in the disease process, additional replication and more mechanistic studies are needed, they note.
“In general, these types of studies are useful for generating hypotheses for future studies, yet they need validation in cell and animal models of [Parkinson’s disease] and other neurodegenerative disorders,” they say.
“To my reading, all the ‘immune’ associations [with Parkinson’s disease] remain tenuous, whether genetic, epidemiologic [or)] biologic,” neurogeneticist Dr. Matthew Farrer, of the University of British Columbia in Vancouver, tells Reuters Health by email.
Dr. Farrer, who was not involved in the current study, cautioned that the confirmatory data set was generated with a genomics tool “originally built about immune content, so it is not without bias in terms of genome-wide discovery.”
He also notes that the component of the study that investigated changes in expression and methylation levels of immune function-related genes in the brain was limited to the frontal cortex or cerebellum.
“I am not sure if this makes much biologic sense … it’s basal ganglia and brainstem nuclei that are preferentially affected/lost in [Parkinson’s disease],” explains Dr. Farrer, whose research focuses on genetic and functional analysis of neurologic and neurodegenerative disorders, particularly Parkinson’s disease.
In addition, none of the “mixed bag” of immune disorders that were studied “are that prevalent in Parkinson’s disease—indeed, the opposite,” Dr. Farrer says. For example, multiple sclerosis is extremely rare in pedigrees with familial parkinsonism, he notes.
“Nor am I aware if parkinsonism is more common in any of these immune conditions,” he said. “Thus, the clinical associations/validity and justification to look at common molecular mechanisms is perhaps not so compelling.”
The study had no commercial funding, and the authors reported no conflicts of interest.
References
- Witoelar A, Jansen IE, Wang Y, et al. Genome-wide pleiotropy between parkinson disease and autoimmune diseases. JAMA Neurol. 2017 Jun 5. doi: 10.1001/jamaneurol.2017.0469. [Epub ahead of print]
- McFarland NR, McFarland KN, Golde TE. Parkinson disease and autoimmune disorders—what can we learn from genome-wide pleiotropy? JAMA Neurol. 2017 Jun 5. doi: 10.1001/jamaneurol.2017.0843. [Epub ahead of print]