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Sjögren’s Syndrome: Interface of Immunology and Neurology

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Neurorheumatology

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Abstract

Sjögren’s syndrome (SS) is characterized by dry eyes and dry mouth, due to focal lymphocytic infiltrates of the lacrimal and salivary glands. SS patients also have a spectrum of extraglandular manifestations including skin, joint, pulmonary, renal, cardiovascular, hematopoietic, neurological, and lymphoid proliferation. Indeed, the neurological manifestations are among the most challenging perplexities for the clinical rheumatologists and other specialists involved in their care. In addition, SS patients have a high incidence of fatigue, self-described cognitive impairment, and myalgias that baffle the rheumatologist because they do not correlate closely with either glandular or extraglandular manifestations. An understanding of the neuropathies in SS seems a good starting point in approaching the unmet needs of the SS patient. In particular, it is necessary to move beyond the narrowly defined “innate” and “adaptive” immune response (i.e., T-cell-directed B-cell production of autoantibodies) to the more general “danger hypothesis” that includes interactions of the immune system with the brain (hypothalamic and adrenal axis), midbrain amplification of neurokines and pain pathways, and prostaglandin pathways that play a role in vascular tone and blood pressure regulation.

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References

  1. Birnbaum J. Peripheral nervous system manifestations of Sjögren syndrome: clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies. Neurologist. 2010;16(5):287–97.

    Article  Google Scholar 

  2. Fox RI, Fox CM. Sjögren syndrome: why do clinical trials fail? Rheum Dis Clin N Am. 2016;42(3):519–30.

    Article  Google Scholar 

  3. Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol. 2001;13(1):114–9.

    Article  CAS  Google Scholar 

  4. Konttinen YT, Sorsa T, Hukkanen M, Segerberg M, Kuhlefelt-Sundström M, Malmström M, et al. Topology of innervation of labial salivary glands by protein gene product 9.5 and synaptophysin immunoreactive nerves in patients with Sjogren’s syndrome. J Rheumatol. 1992;19(1):30–7.

    CAS  PubMed  Google Scholar 

  5. Konttinen YT, Tensing EK, Laine M, Porola P, Tornwall J, Hukkanen M. Abnormal distribution of aquaporin-5 in salivary glands in the nod mouse model for Sjogren’s syndrome. J Rheumatol. 2005;32(6):1071–5.

    CAS  PubMed  Google Scholar 

  6. Konttinen YT, Halinen S, Hanemaaijer R, Sorsa T, Hietanen J, Ceponis A, et al. Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjogren’s syndrome. Matrix Biol. 1998;17(5):335–47.

    Article  CAS  Google Scholar 

  7. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. A unified theory of the role of the ocular surface in dry eye. Adv Exp Med Biol. 1998;438:643–51.

    Article  CAS  Google Scholar 

  8. Belmonte C, Gallar J. Cold thermoreceptors, unexpected players in tear production and ocular dryness sensations. Invest Ophthalmol Vis Sci. 2011;52(6):3888–92.

    Article  Google Scholar 

  9. Dartt DA. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Prog Retin Eye Res. 2009;28(3):155–77.

    Article  Google Scholar 

  10. Moulton EA, Becerra L, Rosenthal P, Borsook D. An approach to localizing corneal pain representation in human primary somatosensory cortex. PLoS One. 2012;7(9):e44643.

    Article  CAS  Google Scholar 

  11. Jonsson R, Gordon TP, Konttinen YT. Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjogren’s syndrome. Curr Rheumatol Rep. 2003;5(4):311–6.

    Article  Google Scholar 

  12. Tornwall J, Uusitalo H, Hukkanen M, Sorsa T, Konttinen YT. Distribution of vasoactive intestinal peptide (VIP) and its binding sites in labial salivary glands in Sjogren’s syndrome and in normal controls. Clin Exp Rheumatol. 1994;12(3):287–92.

    CAS  PubMed  Google Scholar 

  13. Cekic C, Linden J. Purinergic regulation of the immune system. Nat Rev Immunol. 2016;16(3):177–92.

    Article  CAS  Google Scholar 

  14. Kondo T, Inoue H, Usui T, Mimori T, Tomimoto H, Vernino S, et al. Autoimmune autonomic ganglionopathy with Sjögren’s syndrome: significance of ganglionic acetylcholine receptor antibody and therapeutic approach. Auton Neurosci. 2009;146(1):33–5.

    Article  CAS  Google Scholar 

  15. Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000;343(12):847–55.

    Article  CAS  Google Scholar 

  16. Andonopoulos A, Ballas C. Autonomic cardiovascular neuropathy in primary Sjogren’s syndrome. Rheumatol Int. 1995;15(3):127–9.

    Article  CAS  Google Scholar 

  17. Wright RA, Grant IA, Low PA. Autonomic neuropathy associated with sicca complex. J Auton Nerv Syst. 1999;75(1):70–6.

    Article  CAS  Google Scholar 

  18. Freeman R. Autonomic peripheral neuropathy. Lancet. 2005;365(9466):1259–70.

    Article  CAS  Google Scholar 

  19. Harboe ETA, Maroni S, Gøransson LG, Greve OJ, Beyer MK, Herigstad A, Kvaløy JT, Omdal R. Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study. Ann Rhem Dis. 2009;68(10):1541–6.

    Article  CAS  Google Scholar 

  20. Segal BM, Pogatchnik B, Holker E, Liu H, Sloan J, Rhodus N, et al. Primary Sjogren’s syndrome: cognitive symptoms, mood, and cognitive performance. Acta Neurol Scand [Research Support, NIH, Extramural Research Support, Non-US Gov’t]. 2012;125(4):272–8.

    CAS  Google Scholar 

  21. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology [Consensus Development Conference Practice Guideline Research Support, Non-US Gov’t]. 2015;85(2):177–89.

    Google Scholar 

  22. Carvalho DCTT, Freitas DS, Kleinpaul R, Talim NC, Lana-Peixoto MA. Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu. Arq Neuropsiquiatr. 2014;72(8):619–24.

    Article  Google Scholar 

  23. Blanc FLN, Jung B, Kleitz C, Di Bitonto L, Cretin B, Collongues N, Sordet C, Fleury M, Poindron V, Gottenberg JE, Anne O, Lipsker D, Martin T, Sibilia J, de Seze J. Cognitive dysfunction and dementia in primary Sjögren’s syndrome. ISRN Neurol. 2013;2013:501327.

    Article  Google Scholar 

  24. Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol [Research Support, Non-US Gov’t Review]. 2016;15(3):292–303.

    Google Scholar 

  25. Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med. 2000;343(5):338–44.

    Article  CAS  Google Scholar 

  26. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20(1):197–216.

    Article  CAS  Google Scholar 

  27. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12(1):991–1045.

    Article  CAS  Google Scholar 

  28. Blalock J. The immune system as the sixth sense. J Intern Med. 2005;257(2):126–38.

    Article  CAS  Google Scholar 

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Acknowledgments

Dr. Robert I. Fox and Dr. Julius Birnbaum would like to acknowledge Dr. Carla Martin Fox for her contribution toward this chapter.

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Authors and Affiliations

  1. Rheumatology Clinic, Department of Rheumatology, Scripps Memorial Hospital and Research Foundation, La Jolla, CA, USA

    Robert I. Fox

  2. Division of Rheumatology, Department of Medicine, The Jerome Greene Sjogren’s Center, Baltimore, MD, USA

    Julius Birnbaum

  3. Department of Neurology, Bayview Medical Center, Baltimore, MD, USA

    Julius Birnbaum

Authors
  1. Robert I. Fox
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  2. Julius Birnbaum
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Editor information

Editors and Affiliations

  1. Division of Neuroimmunology, University of Iowa, Iowa City, IA, USA

    Tracey A. Cho

  2. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Shamik Bhattacharyya

  3. Division of Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Simon Helfgott

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Fox, R.I., Birnbaum, J. (2019). Sjögren’s Syndrome: Interface of Immunology and Neurology. In: Cho, T., Bhattacharyya, S., Helfgott, S. (eds) Neurorheumatology. Springer, Cham. https://doi.org/10.1007/978-3-030-16928-2_6

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  • DOI: https://doi.org/10.1007/978-3-030-16928-2_6

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16927-5

  • Online ISBN: 978-3-030-16928-2

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