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

Zachary A Miller, Virginia E Sturm, Gamze Balci Camsari, Anna Karydas, Jennifer S Yokoyama, Lea T Grinberg, Adam L Boxer, Howard J Rosen, Katherine P Rankin, Maria Luisa Gorno-Tempini, Giovanni Coppola, Daniel H Geschwind, Rosa Rademakers, William W Seeley, Neill R Graff-Radford, Bruce L Miller, Zachary A Miller, Virginia E Sturm, Gamze Balci Camsari, Anna Karydas, Jennifer S Yokoyama, Lea T Grinberg, Adam L Boxer, Howard J Rosen, Katherine P Rankin, Maria Luisa Gorno-Tempini, Giovanni Coppola, Daniel H Geschwind, Rosa Rademakers, William W Seeley, Neill R Graff-Radford, Bruce L Miller

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.

Figures

Figure. Autoimmune prevalence in C9 and FTD/MND
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.

References

    1. Miller ZA, Rankin KP, Graff-Radford NR, et al. . TDP-43 frontotemporal lobar degeneration and autoimmune disease. J Neurol Neurosurg Psychiatry 2013;84:956–962.
    1. Mackenzie IRA, Neumann M, Baborie A, et al. . A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011;122:111–113.
    1. Snowden J, Neary D, Mann D. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 2007;114:31–38.
    1. Ng AS, Rademakers R, Miller BL. Frontotemporal dementia: a bridge between dementia and neuromuscular disease. Ann NY Acad Sci 2015;1338:71–93.
    1. Ling S, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 2013;79:416–438.
    1. Appel SH, Stockton-Appel V, Stewart SS, Kerman RH. Amyotrophic lateral sclerosis: associated clinical disorders and immunological evaluations. Arch Neurol 1986;43:234–238.
    1. Appel SH, Smith RG, Engelhardt JI, Stefani E. Evidence for autoimmunity in amyotrophic lateral sclerosis. J Neurol Sci 1993;118:169–174.
    1. Turner MR, Goldacre R, Ramagopalan S, Talbot K, Goldacre MJ. Autoimmune disease preceding amyotrophic lateral sclerosis: an epidemiologic study. Neurology 2013;81:1222–1225.
    1. Neary D, Snowden JS, Gustafson L, et al. . Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.
    1. Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 1994;124(suppl):96–107.
    1. Litvan I, Agid Y, Calne D, et al. . Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996;47:1–9.
    1. Josephs KA, Petersen RC, Knopman DS, et al. . Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology 2006;66:41–48.
    1. Atanasio A, Decman V, White D, et al. . C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice. Sci Rep 2016;6:23204.
    1. O'Rourke J, Bogdanik L, Yáñez A, et al. . C9orf72 is required for proper macrophage and microglial function in mice. Science 2016;351:1324–1329.
    1. Burberry A, Suzuki N, Wang JY, et al. . Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci Transl Med 2016;8:347ra93.
    1. Sudria-Lopez E, Koppers M, de Wit M, et al. . Full ablation of C9orf72 in mice causes immune system-related pathology and neoplastic events but no motor neuron defects. Acta Neuropathol 2016;132:145–147.
    1. Poloni M, Facchetti D, Mai R, et al. . Circulating levels of tumour necrosis factor-[alpha] and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci Lett 2000;287:211–214.
    1. Kuhle J, Lindberg R, Regeniter A, et al. . Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol 2009;16:771–774.
    1. McGeer P, McGeer E. Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 2002;26:459–470.
    1. Butovsky O, Siddiqui S, Gabriely G, et al. . Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 2012;122:3063–3087.
    1. Liu C, Batliwalla F, Li W, et al. . Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. Mol Med 2008;14:575–581.
    1. Ferrari R, Hernandez DG, Nalls MA, et al. . Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 2014;13:686–699.
    1. Cirulli ET, Lasseigne BN, Petrovski S, et al. . Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 2015;347:1436–1441.
    1. Pottier C, Bieniek KF, Finch N, et al. . Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease. Acta Neuropathol 2015;130:77–92.
    1. Freischmidt A, Wieland T, Richter B, et al. . Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 2015;18:631–636.
    1. Bultema JJ, Ambrosio AL, Burek CL, Di Pietro SM. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. J Biol Chem 2012;287:19550–19563.
    1. Waterman EA, Gawkrodger DJ, Watson PF, Weetman AP, Kemp EH. Autoantigens in vitiligo identified by the serological selection of a phage-displayed melanocyte cDNA expression library. J Invest Dermatol 2010;130:230–240.
    1. Zhang D, Iyer LM, He F, Aravind L. Discovery of novel DENN proteins: implications for the evolution of eukaryotic intracellular membrane structures and human disease. Front Genet 2012;3:283.
    1. Mantegazza AR, Magalhaes JG, Amigorena S, Marks MS. Presentation of phagocytosed antigens by MHC class I and II. Traffic 2013;14:135–152.
    1. Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry 2011;72:126–133.
    1. Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002;58:1615–1621.
    1. Williams KL, Fifita JA, Vucic S, et al. . Pathophysiological insights into ALS with C9ORF72 expansions. J Neurol Neurosurg Psychiatry 2013;84:931–935.
    1. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology 2003;61:349–354.
    1. Ji J, Sundquist J, Sundquist K. Gender-specific incidence of autoimmune diseases from national registers. J Autoimmun 2016;69:102–106.
    1. Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 2008;173:600–609.
    1. Tang W, Lu Y, Tian QY, et al. . The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 2011;332:478–484.
    1. Helmick CG, Felson DT, Lawrence RC, et al. . Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part I. Arthritis Rheum 2008;58:15–25.
    1. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. . The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 2007;5:1424–1429.

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