Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study
IntroductionThe polyspecific intrathecal immune response (PSIIR), aka MRZ reaction (M = measles, R = rubella, Z = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1193015/full |
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| author | Felix Brauchle Daniel Rapp Makbule Senel André Huss Jens Dreyhaupt Veronika Klose Marie Süße Klarissa Hanja Stürner Frank Leypoldt Frank Leypoldt Hayrettin Tumani Jan Lewerenz |
| author_facet | Felix Brauchle Daniel Rapp Makbule Senel André Huss Jens Dreyhaupt Veronika Klose Marie Süße Klarissa Hanja Stürner Frank Leypoldt Frank Leypoldt Hayrettin Tumani Jan Lewerenz |
| author_sort | Felix Brauchle |
| collection | DOAJ |
| description | IntroductionThe polyspecific intrathecal immune response (PSIIR), aka MRZ reaction (M = measles, R = rubella, Z = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF) biomarker for multiple sclerosis (MS), a chronic autoimmune-inflammatory neurological disease (CAIND) of the central nervous system (CNS) usually starting in young adulthood, the full spectrum of CAINDs with a positive PSIIR remains ill defined.MethodsIn this retrospective, cross-sectional study, patients with CSF-positive oligoclonal bands (OCB) and - to enrich for non-MS diagnoses - aged ≥50 years were enrolled.ResultsOf 415 with PSIIR testing results (MRZ, HSV optional), 76 were PSIIR-positive. Of these, 25 (33%) did not meet the diagnostic criteria for MS spectrum diseases (MS-S) comprising clinically or radiologically isolated syndrome (CIS/RIS) or MS. PSIIR-positive non-MS-S phenotypes were heterogenous with CNS, peripheral nerve and motor neuron involvement and often defied unequivocal diagnostic classification. A rating by neuroimmunology experts suggested non-MS CAINDs in 16/25 (64%). Long-term follow-up available in 13 always showed a chronically progressive course. Four of five responded to immunotherapy. Compared to MS-S patients, non-MS CAIND patients showed less frequent CNS regions with demyelination (25% vs. 75%) and quantitative IgG IIS (31% vs. 81%). MRZ-specific IIS did not differ between both groups, while additional HSV-specific IIS was characteristic for non-MS CAIND patients.DiscussionIn conclusion, PSIIR positivity occurs frequently in non-MS-S patients ≥50 years. Although sometimes apparently coincidental, the PSIIR seems to represent a suitable biomarker for previously unnoticed chronic neurologic autoimmunities, which require further characterization. |
| first_indexed | 2024-03-13T05:26:36Z |
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| id | doaj.art-93c30f719cff48418790e13cea2f0159 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-13T05:26:36Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-93c30f719cff48418790e13cea2f01592023-06-15T05:57:58ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-06-011410.3389/fneur.2023.11930151193015Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional studyFelix Brauchle0Daniel Rapp1Makbule Senel2André Huss3Jens Dreyhaupt4Veronika Klose5Marie Süße6Klarissa Hanja Stürner7Frank Leypoldt8Frank Leypoldt9Hayrettin Tumani10Jan Lewerenz11Department of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyInstitute of Epidemiology and Medical Biometry, Ulm University, Ulm, GermanyGerman Center for Neurodegenerative Diseases (DNZE), Campus Ulm, Ulm, GermanyDepartment of Neurology, University Medicine Greifswald, Greifswald, GermanyDepartment of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyNeuroimmunology, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyIntroductionThe polyspecific intrathecal immune response (PSIIR), aka MRZ reaction (M = measles, R = rubella, Z = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF) biomarker for multiple sclerosis (MS), a chronic autoimmune-inflammatory neurological disease (CAIND) of the central nervous system (CNS) usually starting in young adulthood, the full spectrum of CAINDs with a positive PSIIR remains ill defined.MethodsIn this retrospective, cross-sectional study, patients with CSF-positive oligoclonal bands (OCB) and - to enrich for non-MS diagnoses - aged ≥50 years were enrolled.ResultsOf 415 with PSIIR testing results (MRZ, HSV optional), 76 were PSIIR-positive. Of these, 25 (33%) did not meet the diagnostic criteria for MS spectrum diseases (MS-S) comprising clinically or radiologically isolated syndrome (CIS/RIS) or MS. PSIIR-positive non-MS-S phenotypes were heterogenous with CNS, peripheral nerve and motor neuron involvement and often defied unequivocal diagnostic classification. A rating by neuroimmunology experts suggested non-MS CAINDs in 16/25 (64%). Long-term follow-up available in 13 always showed a chronically progressive course. Four of five responded to immunotherapy. Compared to MS-S patients, non-MS CAIND patients showed less frequent CNS regions with demyelination (25% vs. 75%) and quantitative IgG IIS (31% vs. 81%). MRZ-specific IIS did not differ between both groups, while additional HSV-specific IIS was characteristic for non-MS CAIND patients.DiscussionIn conclusion, PSIIR positivity occurs frequently in non-MS-S patients ≥50 years. Although sometimes apparently coincidental, the PSIIR seems to represent a suitable biomarker for previously unnoticed chronic neurologic autoimmunities, which require further characterization.https://www.frontiersin.org/articles/10.3389/fneur.2023.1193015/fullpolyspecific intrathecal immune responseMRZ reactionmultiple sclerosisneuroinflammationautoimmue disease |
| spellingShingle | Felix Brauchle Daniel Rapp Makbule Senel André Huss Jens Dreyhaupt Veronika Klose Marie Süße Klarissa Hanja Stürner Frank Leypoldt Frank Leypoldt Hayrettin Tumani Jan Lewerenz Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study Frontiers in Neurology polyspecific intrathecal immune response MRZ reaction multiple sclerosis neuroinflammation autoimmue disease |
| title | Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study |
| title_full | Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study |
| title_fullStr | Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study |
| title_full_unstemmed | Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study |
| title_short | Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases – a retrospective cross-sectional study |
| title_sort | clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non multiple sclerosis chronic autoimmune inflammatory neurological diseases a retrospective cross sectional study |
| topic | polyspecific intrathecal immune response MRZ reaction multiple sclerosis neuroinflammation autoimmue disease |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1193015/full |
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