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Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab

We report the case of a patient with PIGT mutations who experienced recurrent aseptic meningitis 121 times over 16 years before developing paroxysmal nocturnal haemoglobinuria (PNH). Each episode was preceded by urticaria and arthralgia. After developing PNH, haemolysis occurred prior to meningitis....

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Detalles Bibliográficos
Autores principales: Kawamoto, Michi, Murakami, Yoshiko, Kinoshita, Taroh, Kohara, Nobuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169622/
https://www.ncbi.nlm.nih.gov/pubmed/30262533
http://dx.doi.org/10.1136/bcr-2018-225910
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author Kawamoto, Michi
Murakami, Yoshiko
Kinoshita, Taroh
Kohara, Nobuo
author_facet Kawamoto, Michi
Murakami, Yoshiko
Kinoshita, Taroh
Kohara, Nobuo
author_sort Kawamoto, Michi
collection PubMed
description We report the case of a patient with PIGT mutations who experienced recurrent aseptic meningitis 121 times over 16 years before developing paroxysmal nocturnal haemoglobinuria (PNH). Each episode was preceded by urticaria and arthralgia. After developing PNH, haemolysis occurred prior to meningitis. Flow cytometry revealed deficiency of the glycophosphatidylinositol (GPI)-anchored complement regulatory proteins, CD59 and CD55, and he was diagnosed with PNH. All the symptoms disappeared on administering eculizumab, an anti-C5 antibody. We did not detect mutation in PIGA, which is regarded as the cause of PNH. However, we detected a germ-line mutation and a somatic microdeletion in chromosome 20q including PIGT; PIGT is essential for transferring GPI anchor to the precursors of CD59 and CD55, which play important roles in complement regulation. Loss of these proteins leads to complement overactivation, causing inflammatory symptoms, including recurrent meningitis. PIGT mutations should be considered a novel pathogenesis of recurrent meningitis of unknown aetiology.
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spelling pubmed-61696222018-10-05 Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab Kawamoto, Michi Murakami, Yoshiko Kinoshita, Taroh Kohara, Nobuo BMJ Case Rep Findings That Shed New Light on the Possible Pathogenesis of a Disease or an Adverse Effect We report the case of a patient with PIGT mutations who experienced recurrent aseptic meningitis 121 times over 16 years before developing paroxysmal nocturnal haemoglobinuria (PNH). Each episode was preceded by urticaria and arthralgia. After developing PNH, haemolysis occurred prior to meningitis. Flow cytometry revealed deficiency of the glycophosphatidylinositol (GPI)-anchored complement regulatory proteins, CD59 and CD55, and he was diagnosed with PNH. All the symptoms disappeared on administering eculizumab, an anti-C5 antibody. We did not detect mutation in PIGA, which is regarded as the cause of PNH. However, we detected a germ-line mutation and a somatic microdeletion in chromosome 20q including PIGT; PIGT is essential for transferring GPI anchor to the precursors of CD59 and CD55, which play important roles in complement regulation. Loss of these proteins leads to complement overactivation, causing inflammatory symptoms, including recurrent meningitis. PIGT mutations should be considered a novel pathogenesis of recurrent meningitis of unknown aetiology. BMJ Publishing Group 2018-09-27 /pmc/articles/PMC6169622/ /pubmed/30262533 http://dx.doi.org/10.1136/bcr-2018-225910 Text en © BMJ Publishing Group Limited 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Findings That Shed New Light on the Possible Pathogenesis of a Disease or an Adverse Effect
Kawamoto, Michi
Murakami, Yoshiko
Kinoshita, Taroh
Kohara, Nobuo
Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title_full Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title_fullStr Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title_full_unstemmed Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title_short Recurrent aseptic meningitis with PIGT mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
title_sort recurrent aseptic meningitis with pigt mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab
topic Findings That Shed New Light on the Possible Pathogenesis of a Disease or an Adverse Effect
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169622/
https://www.ncbi.nlm.nih.gov/pubmed/30262533
http://dx.doi.org/10.1136/bcr-2018-225910
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