Different pain phenotypes are associated with anti-Caspr2 autoantibodies
Authors: Greguletz Patrik , Plötz Maria , Baade-Büttner Carolin , Bien Christian G. , Eisenhut Katharina , Geis Christian , Handreka Robert , Klausewitz Jaqueline , Körtvelyessy Peter , Kovac Stjepana , Kraft Andrea , Lewerenz Jan , Malter Michael , Nagel Michael , von Podewils Felix , Prüß Harald , Rada Anna , Rau Johanna , Rauer Sebastian , Rößling Rosa , Seifert-Held Thomas , Siebenbrodt Kai , Sühs Kurt-Wolfram , Tauber Simone C. , Thaler Franziska , Wagner Judith , Wickel Jonathan , Leypoldt Frank , Rittner Heike L. , Sommer Claudia , Villmann Carmen , Doppler Kathrin ,   the GENERATE study group, Adelmann Michael , Appeltshauser Luise , Ayzenberg Ilya , van Baalen Andreas , Baatz Sebastian , Bähr Oliver , Balint Bettina , Bauer Sebastian , Baumgartner Annette , Becker Stefanie , Benesch Sonka , Berger Robert , Berger Birgit , Berghoff Martin , Berning Sascha , Bernsen Sarah , Berthele Achim , Bien Christian , Bien Corinna , Binder Andreas , Bittner Stefan , Bittner Daniel , Blaes Franz , Blaschek Astrid , Bohn Amelie , Castro-Gomez Sergio , Dargvainiene Justina , Deba Timo , Decker Julia Maren , Dik Andre , Dominik Juliane , Dreesmann Mona , Ebinger Friedrich , Edelhoff Lena , Ehrhardt Laura , Ehrlich Sven , Emmer Alexander , Endres Dominique , Entscheva Marina , Esser Daniela , Etgen Thorleif , Faiss Jürgen Hartmut , Falk Kim Kristin , Fazeli Walid , Finke Alexander , Finke Carsten , Fitzner Dirk , Flotats-Bastardas Marina , Fousse Mathias , Freilinger Tobias , Friedemann Paul , Friese Manuel , Gallus Marco , Gebhard Marcel , Gorsler Anna , Grau Armin , Grauer Oliver , Greshake Britta , Groß Catharina , Grüter Thomas , Haghikia Aiden , Hansen Niels , Harmel Jens , Harms Antonia , Alizo Yetzenia Dubraska Haro , Häusler Martin , Havla Joachim , Ha-Yeun Chung , Heide Wolfgang , Held Valentin , Hellwig Kerstin , Hillebrand Philip , Hoffmann Frank , Hofmann Christian , Oy Ulrich Hofstadt-van , Huppke Peter , Huttner Hagen , Ismail Fatme Seval , Jansen Martina , Jansen Mareike , Juranek Aleksandra , Karenfort Michael , Kaufmann Max , Kellinghaus Christoph , Kerin Constanze , Knake Susanne , Knierim Ellen , Körtvélyessy Peter , Krämer Markus , Kraus Verena , Krogias Christos , Kuhlenbäumer Gregor , Kümpfel Tanja , Lehrich Christoph , Linsa Andeas , Lünemann Jan , Madlener Marie , Margraf Niels , Martinez Quesada Carlos , Meister Monika , Melzer Nico , Melzer Kristin Stefanie , Menge Til , Meuth Sven , Meyer zu Hörste Gerd , Möller Fabian , Mono Marie-Luise , Mues Sigrid , Obrocki Jost , Penner Loana , Pfeffer Lena Kristina , Pfefferkorn Thomas , Pfeuffer Steffen , Philipsen Alexandra , Piepgras Johannes , von Poderwils Felix , Pompsch Mosche , Priller Josef , Pröbstel Anne-Katrin , Rapp Daniel , Ratuszny Dominica , Rau Johanna Maria Helena , Räuber Saskia Jania , Rehmann Robert , Reichen Ina , Reimann Gernot , Reinecke Raphael , Retzlaff Nele , Ringelstein Marius , Rohner Henrik , Rosenow Felix , Rostasy Kevin , Rüber Theodor , Rüegg Stephan , Saathoff Yannic , Schaumberg Jens , Schilling Ruth , Schimmel Mareike , Schmidt Jens , Schmütz Ina-Isabelle , Schneider Hauke , Schramm Patrick , Schreiber Stephan , Schreyer Gesa , Schröder Ina , Schuster Simon , Seidel Günter , Seifert Frank , Senel Makbule , Simova Olga , Spiegler Juliane , Stammel Oliver , Steinbrecher Andeas , Stolze Henning , Stoppe Muriel , Storm Karin van`s Gravesande , Strippel Christine , Sturm Dietrich , Stürner Klarissa Hanja , Syrbe Steffen , Tacik Pawel , Tauber Simone , Then Bergh Florian , Tietz Anja , Trebst Corinna , Trendelenburg George , Trollmann Regina , Tsaktanis Thanos , Tumani Hayrettin , Türedi Methap , Urbanek Christian , Vogel Niklas , Vogtmann Max , von Mering Matthias , Wagner Jan , Wandinger Klaus-Peter , Weissert Robert , Wildemann Brigitte , Witt Karsten , Wurdack Kartharina , Zieger Lara 
Published: February 2024

Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.