Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6)
IntroductionAutosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1118369/full |
| _version_ | 1797901827640918016 |
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| author | Friederike Ufer Susanne M. Ziegler Marcus Altfeld Manuel A. Friese |
| author_facet | Friederike Ufer Susanne M. Ziegler Marcus Altfeld Manuel A. Friese |
| author_sort | Friederike Ufer |
| collection | DOAJ |
| description | IntroductionAutosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib.MethodsWe collected clinical data of an extended family with RVCLS (TREX1 pVAL235Glyfs*6). Within this family we identified a 45-year-old woman as index patient that we treated experimentally for 5 years and prospectively collected clinical, laboratory and imaging data.ResultsWe report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated CXCL10 mRNA in peripheral blood monocular cells (PBMCs) and a reduction of antinuclear autoantibodies.DiscussionWe provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of CXCL10 transcripts in PBMCs as useful biomarker of disease activity. |
| first_indexed | 2024-04-10T09:08:06Z |
| format | Article |
| id | doaj.art-d09d1580c69d441a9f0008c09c94b4b5 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-10T09:08:06Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-d09d1580c69d441a9f0008c09c94b4b52023-02-21T05:32:04ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-02-011410.3389/fneur.2023.11183691118369Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6)Friederike Ufer0Susanne M. Ziegler1Marcus Altfeld2Manuel A. Friese3Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Virus Immunology, Leibniz Institute for Virology, Hamburg, GermanyDepartment of Virus Immunology, Leibniz Institute for Virology, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyIntroductionAutosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib.MethodsWe collected clinical data of an extended family with RVCLS (TREX1 pVAL235Glyfs*6). Within this family we identified a 45-year-old woman as index patient that we treated experimentally for 5 years and prospectively collected clinical, laboratory and imaging data.ResultsWe report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated CXCL10 mRNA in peripheral blood monocular cells (PBMCs) and a reduction of antinuclear autoantibodies.DiscussionWe provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of CXCL10 transcripts in PBMCs as useful biomarker of disease activity.https://www.frontiersin.org/articles/10.3389/fneur.2023.1118369/fullTREX1brain vascular disorderhereditary autoinflammatory diseasesCXCL10immunosuppressionJAK inhibition |
| spellingShingle | Friederike Ufer Susanne M. Ziegler Marcus Altfeld Manuel A. Friese Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) Frontiers in Neurology TREX1 brain vascular disorder hereditary autoinflammatory diseases CXCL10 immunosuppression JAK inhibition |
| title | Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) |
| title_full | Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) |
| title_fullStr | Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) |
| title_full_unstemmed | Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) |
| title_short | Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6) |
| title_sort | case report jak inhibition as promising treatment option of fatal rvcls due to trex1 mutation pval235glyfs 6 |
| topic | TREX1 brain vascular disorder hereditary autoinflammatory diseases CXCL10 immunosuppression JAK inhibition |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1118369/full |
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