Autoimmune Disorders of the Nervous System

Riwanti Estiasari
Neurology Department
Faculty of Medicine Universitas Indonesia
Cipto Mangunkusumo Hospital Jakarta
 Target of autoimmune nervous system disease

Secondary to systemic
autoimmune disease
Peripheral Nervous System

Central Nervous System

MOG

MOG
Intracelluar NMDAr AQP4 Myelin
disease
antigen Channel

Gangliosides VGCC ACh-r VGKC

Praneoplastic NMDAr NMOSD Multiple

syndrome encephalitis Sclerosis
Guillain Barre Lambert Myasthenia Neuro-
Syndrome Eaton Gravis myotonia
Neuromyelitis Optica Spectrum Disorders

• Inflammatory CNS syndrome

• Associated with IgG AQP4 Antibody
• Clinically manifestated: optic neuritis,
myelitis and brainstem syndrome
• Typically LETM lesion in spinal cord
• Prevalence ~0.5–4/100,000
• M:F ratio = 1:9

Dean M. Wingerchuk. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology Jul 2015, 85 (2) 177-189;
Pereira, Wildéa & Reiche, Edna & Kallaur, Ana & Ramón, Kaimén. (2015). Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review. Journal of the Neurological Sciences..
 NMOSD and systemic autoimmune disease

• A high proportion of cases of both NMO and NMO associated with

rheumatologic diseases had aquaporin-4 autoantibodies and the
frequency did not differ between these two groups
• The MRI appearance may vary in NMO or systemic disease with optic
neuritis of myelitis
• Most common autoimmune
disease associated with NMO:
• Thyroid diseas
• Myasthenia Gravis
• Celiac disease
• Autoimmune disease that
commonly not associated with
destructive CNS pathology

Dean M Wingerchuk1 and Brian G Weinshenker. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Multiple Sclerosis Journal 18(1) 5–10. 2012
 Mechanism underlying co-association NMO with systemic autoimmune disease

• Common genetic and/or environmental factors that predispose to autoimmunity.

• Systemic autoimmune diseases could facilitate some aspect of the pathogenesis of NMO which is
not entirely understood. Systemic inflammatory factors such as autoantibodies or other
inflammatory mechanisms may contribute to disruption of the blood–brain barrier.

• Some systemic autoimmune diseases may contribute to a common

immunopathological mechanism such as vasculopathy

• The formation of AQP4 autoantibodies is an epiphenomenon, possibly without

direct pathogenic significance, that occurs as a result of secondary autoimmune
sensitization to autoantigens.

Dean M Wingerchuk1 and Brian G Weinshenker. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Multiple Sclerosis Journal 18(1) 5–10. 2012
 AQP4 Ab in Systemic Lupus Erythematosus

• CNS disease in SLE patients : spectrum

of neurologic and psychiatric features
• Pathogenic mechanisms of NPSLE are
include vascular abnormalities,
autoantibodies, and local production of
inflammatory mediators.
• Levels of soluble glial fibrillary acidic
protein (an astrocytic marker) are
markedly elevated in the CSF of NPSLE
patients
• Suggesting that immune activation may
be a general effect of astrocyte damage.

Nasrin Asgari. Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: A predominantly population-based study. Multiple Sclerosis Journal. 2018;24(3):331-339
 AQP4 Ab in Systemic Lupus Erythematosus

MOG IgG 0%

AQP4 Ab 6,70%
• AQP4-IgG autoimmune syndrome
anti-Ro 6,70%
may rarely co-exist with SLE,
anti-rib 16,70%
• Other NMOSD-typical syndromes
anti-dsDNA 60% such as myelitis.
ANA 60%

LA 37%

ACAs 53%

anti-β2GPI 70%

APA 83%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

Nasrin Asgari. Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: A predominantly population-based study. Multiple Sclerosis Journal. 2018;24(3):331-339
 • SjS is a very common
Sjogren Syndrome and NMOSD autoimmune disease with an
estimated prevalence of
approximately 0.5% to 1.0%
of the general population
• Often have co-existing
autoimmune diseases (e.g.,
rheumatoid arthritis, SLE,
Hashimoto thyroiditis,
scleroderma) or hematologic
diseases (e.g., malignant
lymphoma).
• An elevated frequency of
coexisting SjS among the
patients with AQP4-IgG-
positive NMOSD

• The prevalence of SjS is higher among AQP4-IgG-positive than AQP4-IgG-negative patients, with the potential
prevalence of 10–20% at the diagnosis of AQP4-IgG-positive NMOSD.
• Comorbid SjS is more prevalent in females
• Has a higher relapse frequency among AQP4-IgG-positive patients.

Akaishi, T., Takahashi, T., Fujihara, K. et al. Impact of comorbid Sjögren syndrome in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders. J Neurol 268, 1938–1944 (2021).
 Multiple Sclerosis and Other Autoimmune disease

• Positive ANA titer in patients with MS is not rare but did not significantly differ from the
control group.
• Most ANA-positive patients were only positive at the low-range titer.

Alnajashi, H., Alshamrani, F. Prevalence of antinuclear antibody in patients with multiple sclerosis: a case-control study. Egypt J Neurol Psychiatry Neurosurg 57, 27 (2021)
 Multiple Sclerosis and Other Autoimmune disease

• 18.8 % of the MS cohort showed elevated serum autoantibody levels

• only 10.2 % of all MS patients were diagnosed with a further autoimmune disease
• MS patients with disease duration of more than 10 years showed no significant increase of
positive autoantibodies as compared to patients with a more recent disease onset
• MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease
course

Dal-Bianco, A, Wenhoda, F, Rommer, PS, et al. Do elevated autoantibodies in patients with multiple sclerosis matter? Acta Neurol Scand. 2019; 139: 238– 246.
Conclusion

• Autoimmune of nervous system can be found in CNS or PNS

• It can be concomittan with other autoimmune disease
• Autoantibodies in systemic autoimmune disease might contribute in disruption of BBB
• AQP4 Ab rarely found in SLE
• Prevalence of SS is higher in IgG AQP4 positive NMOSD patients
• Autoantibodies level in increased in MS patients but without demographic and clinical
relevance
Thank You