Anti-AQP4 disease

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Anti-AQP4 disease
Other names Neuromyelitis optica spectrum of diseases

Anti-AQP4 diseases, are a group of diseases characterized by auto-antibodies against aquaporin 4.

Contents

After the discovery of anti-AQP4 autoantibody in neuromyelitis optica, it was found that it was also present in some patients with other clinically defined diseases, including multiple sclerosis variants like optic-spinal MS. [1]

The collection of these condition has been named "anti-AQP4 disease" and "neuromyelitis optica spectrum disorders" (NMSD) and they are expected to respond to the same treatments as standard NMO. [2] [ failed verification ] Some authors propose to use the name "autoimmune aquaporin-4 channelopathy" for these diseases, [3] while others prefer a more generic term "AQP4-astrocytopathy" that includes also problems in AQP4 with a non-autoimmune origin. [4] [1] [5]

Clinical Spectrum

After finding the anti-AQP4 autoantibody in cases outside the standard Devic's disease course, the spectrum was expanded. The spectrum is now believed to consist of:

Devic's disease is currently considered a syndrome more than a disease, presenting an overlapping with the wide spectrum of multiple sclerosis in the form of Optic-Spinal MS. [10]

Causes

The reason for the presence of anti-AQP4 autoantibodies is currently unknown. Some researchers have pointed out that it could be paraneoplastic. [11] [ non-primary source needed ] It seems also clear that lupus can produce NMO-IgG autoantibodies sometimes, leading to some cases of lupus-derived NMO. [12] [ non-primary source needed ]

Diagnosis

Differential diagnosis

AQP4-Ab-negative NMO presents problems for diagnosis. The behavior of the oligoclonal bands respect MS[ clarification needed ] can help to establish a more accurate diagnosis. Oligoclonal bands in NMO are rare and they tend to disappear after the attacks, while in MS they are nearly always present and persistent. [13]

It is important to notice for differential diagnosis that, though uncommon, it is possible to have longitudinal lesions in MS. [14]

Other problem for diagnosis is that AQP4ab in MOGab levels can be too low to be detected. Some additional biomarkers have been proposed. [15] [16]

Treatment

Chemical structure of methylprednisolone, which is used to treat attacks Methylprednisolone.svg
Chemical structure of methylprednisolone, which is used to treat attacks

Currently, there is no cure for Devic's disease, but symptoms can be treated. Some patients recover, but many are left with impairment of vision and limbs, which can be severe.[ citation needed ]

Attacks

Attacks are treated with short courses of high dosage intravenous corticosteroids such as methylprednisolone IV.[ citation needed ]

Plasmapheresis can be an effective treatment [8] when attacks progress or do not respond to corticosteroid treatment. Clinical trials for these treatments contain very small numbers, and most are uncontrolled, though some report high success percentage. [17]

Secondary prevention

Until recently, no placebo-controlled trials had established the effectiveness of treatments for the prevention of attacks. Most clinicians agree that long term immunosuppression is required to reduce the frequency and severity of attacks. Commonly used immunosuppressant treatments include azathioprine (Imuran) plus prednisone, mycophenolate mofetil plus prednisone, [18] [ non-primary source needed ] mitoxantrone, intravenous immunoglobulin (IVIG), Rituximab, Soliris and cyclophosphamide. [8] [19]

The disease is known to be auto-antibodies mediated, and (antibody-producing) B-cell depletion has been tried [20] with monoclonal antibodies showing good results. [21] [ non-primary source needed ] Several other disease modifying therapies are being tried. In 2007, Devic's disease was reported to be responsive to glatiramer acetate [18] [ non-primary source needed ] and to low-dose corticosteroids. [22] Use of Mycophenolate mofetil is also currently under research. [23]

Hematopoietic stem cell transplantation (HSCT) is sometimes used in severe cases of NMO. Early data suggested that then-practiced forms of HSCT were very effective only in the short term. [24] However, later study data had most patients thriving, with no relapses within 5 years. [25]

Related Research Articles

<span class="mw-page-title-main">Acute disseminated encephalomyelitis</span> Autoimmune disease

Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.

<span class="mw-page-title-main">Optic neuritis</span> Medical condition

Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.

<span class="mw-page-title-main">Transverse myelitis</span> Medical condition of the spinal cord

Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective transverse implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the terms partial transverse myelitis and partial myelitis are sometimes used to specify inflammation that affects only part of the width of the spinal cord. TM is characterized by weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Signs and symptoms vary according to the affected level of the spinal cord. The underlying cause of TM is unknown. The spinal cord inflammation seen in TM has been associated with various infections, immune system disorders, or damage to nerve fibers, by loss of myelin. As opposed to leukomyelitis which affects only the white matter, it affects the entire cross-section of the spinal cord. Decreased electrical conductivity in the nervous system can result.

<span class="mw-page-title-main">Multiple sclerosis</span> Disease that damages the myelin sheaths around nerves

Multiplesclerosis (MS) is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, visual loss, muscle weakness, and trouble with sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks or building up over time. In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances.

Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. In more than 80% of cases, NMO is caused by immunoglobulin G autoantibodies to aquaporin 4 (anti-AQP4), the most abundant water channel protein in the central nervous system. A subset of anti-AQP4-negative cases is associated with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG). Rarely, NMO may occur in the context of other autoimmune diseases or infectious diseases. In some cases, the etiology remains unknown.

<span class="mw-page-title-main">Myelin oligodendrocyte glycoprotein</span>

Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.

<span class="mw-page-title-main">Pathophysiology of multiple sclerosis</span>

Multiple sclerosis is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damage. The underlying cause is currently unknown. Current research in neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology, provide support for the notion that MS is not a single disease but rather a spectrum.

<span class="mw-page-title-main">Aquaporin-4</span> Protein-coding gene in the species Homo sapiens

Aquaporin-4, also known as AQP-4, is a water channel protein encoded by the AQP4 gene in humans. AQP-4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane. A limited number of aquaporins are found within the central nervous system (CNS): AQP1, 3, 4, 5, 8, 9, and 11, but more exclusive representation of AQP1, 4, and 9 are found in the brain and spinal cord. AQP4 shows the largest presence in the cerebellum and spinal cord grey matter. In the CNS, AQP4 is the most prevalent aquaporin channel, specifically located at the perimicrovessel astrocyte foot processes, glia limitans, and ependyma. In addition, this channel is commonly found facilitating water movement near cerebrospinal fluid and vasculature.

<span class="mw-page-title-main">Lesional demyelinations of the central nervous system</span>

Multiple sclerosis and other demyelinating diseases of the central nervous system (CNS) produce lesions and glial scars or scleroses. They present different shapes and histological findings according to the underlying condition that produces them.

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

<span class="mw-page-title-main">Balo concentric sclerosis</span> Medical condition

Baló's concentric sclerosis is a disease in which the white matter of the brain appears damaged in concentric layers, leaving the axis cylinder intact. It was described by József Mátyás Baló who initially named it "leuko-encephalitis periaxialis concentrica" from the previous definition, and it is currently considered one of the borderline forms of multiple sclerosis.

Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilder's disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.

Eugène Devic was a French neurologist who was a native of Lyon.

Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.

<span class="mw-page-title-main">Tumefactive multiple sclerosis</span> Medical condition

Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.

Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive and dependent. Patients typically present with pain associated with visual loss. CRION is a clinical diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. An accurate antibody test which became available commercially in 2017 has allowed most patients previously diagnosed with CRION to be re-identified as having MOG antibody disease, which is not a diagnosis of exclusion. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids or B-cell depleting therapy. Relapse that occurs after reducing or stopping steroids is a characteristic feature.

MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.

Inebilizumab, sold under the brand name Uplizna, is a medication for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults. Inebilizumab is a humanized mAb that binds to and depletes CD19+ B cells including plasmablasts and plasma cells.

Satralizumab, sold under the brand name Enspryng, is a humanized monoclonal antibody medication that is used for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease. The drug is being developed by Chugai Pharmaceutical, a subsidiary of Roche.

Anti-neurofascin demyelinating diseases refers to health conditions engendered by auto-antibodies against neurofascins, which can produce both central and peripheral demyelination. Some cases of combined central and peripheral demyelination (CCPD) could be produced by them.

References

  1. 1 2 Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (July 2015). "International consensus diagnostic criteria for neuromyelitis optica spectrum disorders". Neurology. 85 (2): 177–89. doi:10.1212/WNL.0000000000001729. PMC   4515040 . PMID   26092914.
  2. ↑ Fujihara K, Sato DK (October 2013). "AQP4 antibody serostatus: Is its luster being lost in the management and pathogenesis of NMO?". Neurology. 81 (14): 1186–8. doi:10.1212/WNL.0b013e3182a6cc23. PMID   23997154. S2CID   35351168.
  3. ↑ Pittock SJ, Lucchinetti CF (February 2016). "Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later". Annals of the New York Academy of Sciences. 1366 (1): 20–39. Bibcode:2016NYASA1366...20P. doi:10.1111/nyas.12794. PMC   4675706 . PMID   26096370.
  4. ↑ Masaki K (October 2015). "Early disruption of glial communication via connexin gap junction in multiple sclerosis, Baló's disease and neuromyelitis optica". Neuropathology. 35 (5): 469–80. doi: 10.1111/neup.12211 . PMID   26016402. S2CID   6371457.
  5. ↑ Masaki K, Suzuki SO, Matsushita T, Matsuoka T, Imamura S, Yamasaki R, Suzuki M, Suenaga T, Iwaki T, Kira J (2013). "Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica". PLOS ONE. 8 (8): e72919. Bibcode:2013PLoSO...872919M. doi: 10.1371/journal.pone.0072919 . PMC   3749992 . PMID   23991165.
  6. ↑ Li Y, Xie P, Lv F, Mu J, Li Q, Yang Q, Hu M, Tang H, Yi J (October 2008). "Brain magnetic resonance imaging abnormalities in neuromyelitis optica". Acta Neurologica Scandinavica. 118 (4): 218–25. doi:10.1111/j.1600-0404.2008.01012.x. PMID   18384459. S2CID   22270592.
  7. ↑ Isobe, Noriko; Yonekawa, Tomomi; Matsushita, Takuya; Masaki, Katsuhisa; Yoshimura, Satoshi; Fichna, Jakub; Chen, Shu; Furmaniak, Jadwiga; Smith, Bernard Rees; Kira, Jun-ichi (2013-05-01). "Clinical Relevance of Serum Aquaporin-4 Antibody Levels in Neuromyelitis Optica". Neurochemical Research. 38 (5): 997–1001. doi:10.1007/s11064-013-1009-0. ISSN   1573-6903. PMID   23456674. S2CID   18623455.
  8. 1 2 3 Wingerchuk, Dean (2006). "Neuromyelitis Optica (Devic's Syndrome)" (PDF). 2006 Rare Neuroimmunologic Disorders Symposium. Archived from the original (PDF) on 2006-09-25. Retrieved 2007-01-05.
  9. ↑ Harmel J, Ringelstein M, Ingwersen J, Mathys C, Goebels N, Hartung HP, Jarius S, Aktas O (December 2014). "Interferon-β-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab". BMC Neurology. 14: 247. doi:10.1186/s12883-014-0247-3. PMC   4301061 . PMID   25516429.
  10. ↑ Lassmann H, Brück W, Lucchinetti C (March 2001). "Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy". Trends in Molecular Medicine. 7 (3): 115–21. doi:10.1016/s1471-4914(00)01909-2. PMID   11286782.
  11. ↑ Iorio R, Rindi G, Erra C, Damato V, Ferilli M, Sabatelli M (May 2015). "Neuromyelitis optica spectrum disorder as a paraneoplastic manifestation of lung adenocarcinoma expressing aquaporin-4". Multiple Sclerosis. 21 (6): 791–4. doi:10.1177/1352458515572241. PMID   25716881. S2CID   22763815.
  12. ↑ Kovacs KT, Kalluri SR, Boza-Serrano A, Deierborg T, Csepany T, Simo M, Rokusz L, Miseta A, Alcaraz N, Czirjak L, Berki T, Molnar T, Hemmer B, Illes Z (August 2016). "Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study". Multiple Sclerosis. 22 (9): 1192–201. doi:10.1177/1352458515613165. PMID   26514978. S2CID   3808843.
  13. ↑ Bergamaschi R, Tonietti S, Franciotta D, Candeloro E, Tavazzi E, Piccolo G, Romani A, Cosi V (February 2004). "Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations". Multiple Sclerosis. 10 (1): 2–4. doi:10.1191/1352458504ms988oa. PMID   14760945. S2CID   11730134.
  14. ↑ Komatsu J, Sakai K, Nakada M, Iwasa K, Yamada M (August 2017). "Long spinal cord lesions in a patient with pathologically proven multiple sclerosis". Journal of Clinical Neuroscience. 42: 106–108. doi:10.1016/j.jocn.2017.03.022. PMID   28465080. S2CID   3443914.
  15. ↑ Arru G, Sechi E, Mariotto S, Farinazzo A, Mancinelli C, Alberti D, Ferrari S, Gajofatto A, Capra R, Monaco S, Deiana GA, Caggiu E, Mameli G, Sechi LA, Sechi GP (2017). "Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder". Multiple Sclerosis Journal – Experimental, Translational and Clinical. 3 (4): 2055217317742425. doi:10.1177/2055217317742425. PMC   5703109 . PMID   29204291.
  16. ↑ Jurynczyk M, Probert F, Yeo T, Tackley G, Claridge TD, Cavey A, Woodhall MR, Arora S, Winkler T, Schiffer E, Vincent A, DeLuca G, Sibson NR, Isabel Leite M, Waters P, Anthony DC, Palace J (December 2017). "Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease". Acta Neuropathologica Communications. 5 (1): 95. doi:10.1186/s40478-017-0495-8. PMC   5718082 . PMID   29208041.
  17. ↑ Morgan SM, Zantek ND, Carpenter AF (June 2014). "Therapeutic plasma exchange in neuromyelitis optica: a case series". Journal of Clinical Apheresis. 29 (3): 171–7. doi:10.1002/jca.21304. PMID   24136389. S2CID   24287933.
  18. 1 2 Gartzen K, Limmroth V, Putzki N (June 2007). "Relapsing neuromyelitis optica responsive to glatiramer acetate treatment". European Journal of Neurology. 14 (6): e12–3. doi:10.1111/j.1468-1331.2007.01807.x. PMID   17539924. S2CID   24668975.
  19. ↑ Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, Bakshi R (July 2006). "Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease)". Archives of Neurology. 63 (7): 957–63. doi:10.1001/archneur.63.7.957. PMID   16831964.
  20. ↑ Matiello M, Jacob A, Wingerchuk DM, Weinshenker BG (June 2007). "Neuromyelitis optica". Current Opinion in Neurology. 20 (3): 255–60. doi:10.1097/WCO.0b013e32814f1c6b. PMID   17495617. S2CID   21483082.
  21. ↑ Evangelopoulos ME, Andreadou E, Koutsis G, Koutoulidis V, Anagnostouli M, Katsika P, Evangelopoulos DS, Evdokimidis I, Kilidireas C (January 2017). "Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up". Journal of the Neurological Sciences. 372: 92–96. doi:10.1016/j.jns.2016.11.016. PMID   28017256. S2CID   206291987.
  22. ↑ Watanabe S, Misu T, Miyazawa I, Nakashima I, Shiga Y, Fujihara K, Itoyama Y (September 2007). "Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis". Multiple Sclerosis. 13 (8): 968–74. doi:10.1177/1352458507077189. PMID   17623727. S2CID   6308153.
  23. ↑ Montcuquet A, Collongues N, Papeix C, Zephir H, Audoin B, Laplaud D, Bourre B, Brochet B, Camdessanche JP, Labauge P, Moreau T, Brassat D, Stankoff B, de Seze J, Vukusic S, Marignier R (September 2017). "Effectiveness of mycophenolate mofetil as first-line therapy in AQP4-IgG, MOG-IgG, and seronegative neuromyelitis optica spectrum disorders". Multiple Sclerosis. 23 (10): 1377–1384. doi:10.1177/1352458516678474. PMID   27885065. S2CID   21685585.
  24. ↑ Burman J, Tolf A, Hägglund H, Askmark H (February 2018). "Autologous haematopoietic stem cell transplantation for neurological diseases". Journal of Neurology, Neurosurgery, and Psychiatry. 89 (2): 147–155. doi:10.1136/jnnp-2017-316271. PMC   5800332 . PMID   28866625.
  25. ↑ Burt, Richard K.; Balabanov, Roumen; Han, Xiaoqiang; Burns, Carol; Gastala, Joseph; Jovanovic, Borko; Helenowski, Irene; Jitprapaikulsan, Jiraporn; Fryer, James P.; Pittock, Sean J. (2019). "Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica". Neurology. 93 (18): e1732–e1741. doi:10.1212/WNL.0000000000008394. PMC   6946475 . PMID   31578302.
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