Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity
Objective: While multiple sclerosis (MS) is considered the cornerstone of autoimmune demyelinating CNS disorders, systemic autoimmune diseases (SADs) are important MS mimickers. We sought to explore whether distinct clinical, laboratory, and imaging characteristics along with quantitation of periphe...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.898049/full |
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| author | Dimitris K. Karathanasis Anna Rapti Adrianos Nezos Charalampos Skarlis Constantinos Kilidireas Clio P. Mavragani Clio P. Mavragani Clio P. Mavragani Maria Eleftheria Evangelopoulos |
| author_facet | Dimitris K. Karathanasis Anna Rapti Adrianos Nezos Charalampos Skarlis Constantinos Kilidireas Clio P. Mavragani Clio P. Mavragani Clio P. Mavragani Maria Eleftheria Evangelopoulos |
| author_sort | Dimitris K. Karathanasis |
| collection | DOAJ |
| description | Objective: While multiple sclerosis (MS) is considered the cornerstone of autoimmune demyelinating CNS disorders, systemic autoimmune diseases (SADs) are important MS mimickers. We sought to explore whether distinct clinical, laboratory, and imaging characteristics along with quantitation of peripheral blood type I interferon (IFN) activity could aid in differentiating between them.Methods: A total of 193 consecutive patients with imaging features suggesting the presence of CNS demyelinating disease with or without relevant clinical manifestations underwent full clinical, laboratory, and imaging evaluation, including testing for specific antibodies against 15 cellular antigens. Expression analysis of type I IFN-inducible genes (MX-1, IFIT-1, and IFI44) was performed by real-time PCR, and a type I IFN score, reflecting type I IFN peripheral activity, was calculated. After joint neurological/rheumatological evaluation and 1 year of follow-up, patients were classified into MS spectrum and CNS autoimmune disorders.Results: While 66.3% (n = 128) of the patients were diagnosed with MS spectrum disorders (predominantly relapsing–remitting MS), 24.9% (n = 48) were included in the CNS autoimmune group, and out of those, one-fourth met the criteria for SAD (6.7% of the cohort, n = 13); the rest (18.1% of the cohort, n = 35), despite showing evidence of systemic autoimmunity, did not fulfill SAD criteria and comprised the “demyelinating disease with autoimmune features” (DAF) subgroup. Compared to the MS spectrum, CNS autoimmune patients were older, more frequently females, with increased rates of hypertension/hyperlipidemia, family history of autoimmunity, cortical dysfunction, anti-nuclear antibody titers ≥1/320, anticardiolipin IgM positivity, and atypical for MS magnetic resonance imaging lesions. Conversely, lower rates of infratentorial and callosal MRI lesions, CSF T2 oligoclonal bands, and IgG-index positivity were observed in CNS autoimmune patients. Patients fulfilling SAD criteria, but not the DAF group, had significantly higher peripheral blood type I IFN scores at baseline compared to MS spectrum [median (IQR)]: 50.18 (152.50) vs. −0.64 (6.75), p-value: 0.0001.Conclusion: Our study suggests that underlying systemic autoimmunity is not uncommon in patients evaluated for possible CNS demyelination. Distinct clinical, imaging and laboratory characteristics can aid in early differentiation between MS and CNS-involving systemic autoimmunity allowing for optimal therapeutic strategies. Activated type I IFN pathway could represent a key mediator among MS-like-presenting SADs and therefore a potential therapeutic target. |
| first_indexed | 2024-04-11T22:43:51Z |
| format | Article |
| id | doaj.art-d6e02b4fde52450282765f3ed15c8a90 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T22:43:51Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-d6e02b4fde52450282765f3ed15c8a902022-12-22T03:58:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.898049898049Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activityDimitris K. Karathanasis0Anna Rapti1Adrianos Nezos2Charalampos Skarlis3Constantinos Kilidireas4Clio P. Mavragani5Clio P. Mavragani6Clio P. Mavragani7Maria Eleftheria Evangelopoulos8First Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceFourth Department of Internal Medicine, School of Medicine, University Hospital Attikon, National and Kapodistrian University of Athens, Haidari, GreeceJoint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, GreeceObjective: While multiple sclerosis (MS) is considered the cornerstone of autoimmune demyelinating CNS disorders, systemic autoimmune diseases (SADs) are important MS mimickers. We sought to explore whether distinct clinical, laboratory, and imaging characteristics along with quantitation of peripheral blood type I interferon (IFN) activity could aid in differentiating between them.Methods: A total of 193 consecutive patients with imaging features suggesting the presence of CNS demyelinating disease with or without relevant clinical manifestations underwent full clinical, laboratory, and imaging evaluation, including testing for specific antibodies against 15 cellular antigens. Expression analysis of type I IFN-inducible genes (MX-1, IFIT-1, and IFI44) was performed by real-time PCR, and a type I IFN score, reflecting type I IFN peripheral activity, was calculated. After joint neurological/rheumatological evaluation and 1 year of follow-up, patients were classified into MS spectrum and CNS autoimmune disorders.Results: While 66.3% (n = 128) of the patients were diagnosed with MS spectrum disorders (predominantly relapsing–remitting MS), 24.9% (n = 48) were included in the CNS autoimmune group, and out of those, one-fourth met the criteria for SAD (6.7% of the cohort, n = 13); the rest (18.1% of the cohort, n = 35), despite showing evidence of systemic autoimmunity, did not fulfill SAD criteria and comprised the “demyelinating disease with autoimmune features” (DAF) subgroup. Compared to the MS spectrum, CNS autoimmune patients were older, more frequently females, with increased rates of hypertension/hyperlipidemia, family history of autoimmunity, cortical dysfunction, anti-nuclear antibody titers ≥1/320, anticardiolipin IgM positivity, and atypical for MS magnetic resonance imaging lesions. Conversely, lower rates of infratentorial and callosal MRI lesions, CSF T2 oligoclonal bands, and IgG-index positivity were observed in CNS autoimmune patients. Patients fulfilling SAD criteria, but not the DAF group, had significantly higher peripheral blood type I IFN scores at baseline compared to MS spectrum [median (IQR)]: 50.18 (152.50) vs. −0.64 (6.75), p-value: 0.0001.Conclusion: Our study suggests that underlying systemic autoimmunity is not uncommon in patients evaluated for possible CNS demyelination. Distinct clinical, imaging and laboratory characteristics can aid in early differentiation between MS and CNS-involving systemic autoimmunity allowing for optimal therapeutic strategies. Activated type I IFN pathway could represent a key mediator among MS-like-presenting SADs and therefore a potential therapeutic target.https://www.frontiersin.org/articles/10.3389/fphar.2022.898049/fulltype I interferon scoremultiple sclerosissystemic autoimmune diseaseMS-likedemyelinationneuropsychiatric lupus |
| spellingShingle | Dimitris K. Karathanasis Anna Rapti Adrianos Nezos Charalampos Skarlis Constantinos Kilidireas Clio P. Mavragani Clio P. Mavragani Clio P. Mavragani Maria Eleftheria Evangelopoulos Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity Frontiers in Pharmacology type I interferon score multiple sclerosis systemic autoimmune disease MS-like demyelination neuropsychiatric lupus |
| title | Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity |
| title_full | Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity |
| title_fullStr | Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity |
| title_full_unstemmed | Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity |
| title_short | Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity |
| title_sort | differentiating central nervous system demyelinating disorders the role of clinical laboratory imaging characteristics and peripheral blood type i interferon activity |
| topic | type I interferon score multiple sclerosis systemic autoimmune disease MS-like demyelination neuropsychiatric lupus |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.898049/full |
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