Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts: Completing the picture

Abstract

Objective: To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts.

Methods: In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ² and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts.

Results: Our combined C9 and FTD/MND cohort has a 12% prevalence of nonthyroid autoimmune disease. The prevalence of nonthyroid autoimmune disease in C9 and FTD/MND is similar to the rates in previously detailed progranulin and semantic variant primary progressive aphasia cohorts and elevated in comparison to previously collected normal control and typical Alzheimer disease cohorts, as well as a newly screened progressive supranuclear palsy cohort. Furthermore, the types of autoimmune disease in this combined C9 and FTD/MND cohort cluster within the same 3 categories previously described in progranulin and semantic variant primary progressive aphasia: inflammatory arthritides, cutaneous conditions, and gastrointestinal disorders.

Conclusions: The association between selective autoimmune disease and neurodegenerative disorders unified by the underlying pathology frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) extends to C9 and FTD/MND cohorts, providing further evidence that select autoimmune inflammation may be intrinsically linked to FTLD-TDP pathophysiology.

Figure. Autoimmune prevalence in C9 and FTD/MND

Retrospective chart review of autoimmune conditions in AD, C9, FTD/MND, NC, and PSP cohorts. Above, prevalence of autoimmune diseases across neurodegenerative cohorts (AD vs total C9 and FTD/MND vs NCs vs PSP), and below, between C9 and FTD/MND groups (FTD/MND without C9 vs C9 FTD/MND vs C9 FTD only). Nothing mentioned refers to individuals for whom there is no mention of any condition found within the screening collection instrument. When individuals possess both a thyroid disorder and another autoimmune disease, they are assigned to the nonthyroid autoimmune category, so as to avoid being counted twice. Thyroid only refers to those who only have thyroid spectrum disorders. AD = Alzheimer disease; C9 = C9ORF72 mutation carrier; FTD = frontotemporal dementia; MND = motor neuron disease; NC = normal control; PSP = progressive supranuclear palsy.