Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

Lorena Martín-Aguilar; Cinta Lleixà; Elba Pascual-Goñi; Marta Caballero-Ávila; Laura Martínez-Martínez; Jordi Díaz-Manera; Ricard Rojas-García; Elena Cortés-Vicente; Janina Turon-Sans; Noemi de Luna; Xavier Suárez-Calvet; Eduard Gallardo; Yusuf Rajabally; Sangeeta Scotton; Bart C. Jacobs; Adája Baars; Andrea Cortese; Elisa Vegezzi; Romana Höftberger; Fritz Zimprich; Cornelia Roesler; Eduardo Nobile-Orazio; Giuseppe Liberatore; Fu Liong Hiew; Alicia Martínez-Piñeiro; Alejandra Carvajal; Raquel Piñar-Morales; Mercedes Usón-Martín; Olalla Albertí; Maria Ángeles López-Pérez; Fabian Márquez; Julio Pardo-Fernández; Laura Muñoz-Delgado; Macarena Cabrera-Serrano; Nicolau Ortiz; Manuel Bartolomé; Özgür Duman; Vera Bril; Darwin Segura-Chávez; Kalliopi Pitarokoili; Claudia Steen; Isabel Illa; Luis Querol

doi:10.1212/NXI.0000000000001098

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

Lorena Martín-Aguilar, Cinta Lleixà, Elba Pascual-Goñi, Marta Caballero-Ávila, Laura Martínez-Martínez, Jordi Díaz-Manera, Ricard Rojas-García, Elena Cortés-Vicente, Janina Turon-Sans, Noemi de Luna, Xavier Suárez-Calvet, Eduard Gallardo, Yusuf Rajabally, Sangeeta Scotton, Bart C. Jacobs, Adája Baars, Andrea Cortese, Elisa Vegezzi, Romana Höftberger, Fritz ZimprichCornelia Roesler, Eduardo Nobile-Orazio, Giuseppe Liberatore, Fu Liong Hiew, Alicia Martínez-Piñeiro, Alejandra Carvajal, Raquel Piñar-Morales, Mercedes Usón-Martín, Olalla Albertí, Maria Ángeles López-Pérez, Fabian Márquez, Julio Pardo-Fernández, Laura Muñoz-Delgado, Macarena Cabrera-Serrano, Nicolau Ortiz, Manuel Bartolomé, Özgür Duman, Vera Bril, Darwin Segura-Chávez, Kalliopi Pitarokoili, Claudia Steen, Isabel Illa, Luis Querol

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Abstract

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Original language	English
Article number	e1098
Journal	Neurology(R) neuroimmunology & neuroinflammation
Volume	9
Issue number	1
DOIs	https://doi.org/10.1212/NXI.0000000000001098
Publication status	Published - 2 Jan 2022

Bibliographical note

Funding Information:
This work is supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain and FEDER under grant FIS19/0140 and personal grant INT20/00080, personal grant GBS-CIDP Foundation to CL, personal grant Rio Hortega CM19/00042 to LMA and the ER20P3AC7624 project of the ACCI call of the CIBERER network, Madrid, Spain. XSC was supported by a Sara Borrell postdoctoral fellowship project CD18/00195, funded by Instituto de Salud Carlos III and cofunded by European Union (ERDF/ESF, A way to make Europe/Investing in your future). A.C. thanks the Medical Research Council (MR/T001712/1), the Fondazione CARIPLO (2019-1836), the Italian Ministry of Health-Ricerca Corrente, the Inherited Neuropathy Consortium (INC) and Fondazione Regionale per la Ricerca Biomedica for grant suport

Funding Information:
The Article Processing Charge was funded by authors.

Publisher Copyright:
© American Academy of Neurology.

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Martín-Aguilar, L., Lleixà, C., Pascual-Goñi, E., Caballero-Ávila, M., Martínez-Martínez, L., Díaz-Manera, J., Rojas-García, R., Cortés-Vicente, E., Turon-Sans, J., de Luna, N., Suárez-Calvet, X., Gallardo, E., Rajabally, Y., Scotton, S., Jacobs, B. C., Baars, A., Cortese, A., Vegezzi, E., Höftberger, R., ... Querol, L. (2022). Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy. Neurology(R) neuroimmunology & neuroinflammation, 9(1), Article e1098. https://doi.org/10.1212/NXI.0000000000001098

@article{2375819ab11541ad99e3ff4772708336,

title = "Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy",

abstract = "BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.",

author = "Lorena Mart{\'i}n-Aguilar and Cinta Lleix{\`a} and Elba Pascual-Go{\~n}i and Marta Caballero-{\'A}vila and Laura Mart{\'i}nez-Mart{\'i}nez and Jordi D{\'i}az-Manera and Ricard Rojas-Garc{\'i}a and Elena Cort{\'e}s-Vicente and Janina Turon-Sans and {de Luna}, Noemi and Xavier Su{\'a}rez-Calvet and Eduard Gallardo and Yusuf Rajabally and Sangeeta Scotton and Jacobs, {Bart C.} and Ad{\'a}ja Baars and Andrea Cortese and Elisa Vegezzi and Romana H{\"o}ftberger and Fritz Zimprich and Cornelia Roesler and Eduardo Nobile-Orazio and Giuseppe Liberatore and Hiew, {Fu Liong} and Alicia Mart{\'i}nez-Pi{\~n}eiro and Alejandra Carvajal and Raquel Pi{\~n}ar-Morales and Mercedes Us{\'o}n-Mart{\'i}n and Olalla Albert{\'i} and L{\'o}pez-P{\'e}rez, {Maria {\'A}ngeles} and Fabian M{\'a}rquez and Julio Pardo-Fern{\'a}ndez and Laura Mu{\~n}oz-Delgado and Macarena Cabrera-Serrano and Nicolau Ortiz and Manuel Bartolom{\'e} and {\"O}zg{\"u}r Duman and Vera Bril and Darwin Segura-Ch{\'a}vez and Kalliopi Pitarokoili and Claudia Steen and Isabel Illa and Luis Querol",

note = "Funding Information: This work is supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain and FEDER under grant FIS19/0140 and personal grant INT20/00080, personal grant GBS-CIDP Foundation to CL, personal grant Rio Hortega CM19/00042 to LMA and the ER20P3AC7624 project of the ACCI call of the CIBERER network, Madrid, Spain. XSC was supported by a Sara Borrell postdoctoral fellowship project CD18/00195, funded by Instituto de Salud Carlos III and cofunded by European Union (ERDF/ESF, A way to make Europe/Investing in your future). A.C. thanks the Medical Research Council (MR/T001712/1), the Fondazione CARIPLO (2019-1836), the Italian Ministry of Health-Ricerca Corrente, the Inherited Neuropathy Consortium (INC) and Fondazione Regionale per la Ricerca Biomedica for grant suport Funding Information: The Article Processing Charge was funded by authors. Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2022",

month = jan,

day = "2",

doi = "10.1212/NXI.0000000000001098",

language = "English",

volume = "9",

journal = "Neurology(R) neuroimmunology & neuroinflammation",

issn = "2332-7812",

publisher = "Lippincott Williams & Wilkins",

number = "1",

}

Martín-Aguilar, L, Lleixà, C, Pascual-Goñi, E, Caballero-Ávila, M, Martínez-Martínez, L, Díaz-Manera, J, Rojas-García, R, Cortés-Vicente, E, Turon-Sans, J, de Luna, N, Suárez-Calvet, X, Gallardo, E, Rajabally, Y, Scotton, S, Jacobs, BC , Baars, A, Cortese, A, Vegezzi, E, Höftberger, R, Zimprich, F, Roesler, C, Nobile-Orazio, E, Liberatore, G, Hiew, FL, Martínez-Piñeiro, A, Carvajal, A, Piñar-Morales, R, Usón-Martín, M, Albertí, O, López-Pérez, MÁ, Márquez, F, Pardo-Fernández, J, Muñoz-Delgado, L, Cabrera-Serrano, M, Ortiz, N, Bartolomé, M, Duman, Ö, Bril, V, Segura-Chávez, D, Pitarokoili, K, Steen, C, Illa, I & Querol, L 2022, 'Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy', Neurology(R) neuroimmunology & neuroinflammation, vol. 9, no. 1, e1098. https://doi.org/10.1212/NXI.0000000000001098

TY - JOUR

T1 - Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

AU - Martín-Aguilar, Lorena

AU - Lleixà, Cinta

AU - Pascual-Goñi, Elba

AU - Caballero-Ávila, Marta

AU - Martínez-Martínez, Laura

AU - Díaz-Manera, Jordi

AU - Rojas-García, Ricard

AU - Cortés-Vicente, Elena

AU - Turon-Sans, Janina

AU - de Luna, Noemi

AU - Suárez-Calvet, Xavier

AU - Gallardo, Eduard

AU - Rajabally, Yusuf

AU - Scotton, Sangeeta

AU - Jacobs, Bart C.

AU - Baars, Adája

AU - Cortese, Andrea

AU - Vegezzi, Elisa

AU - Höftberger, Romana

AU - Zimprich, Fritz

AU - Roesler, Cornelia

AU - Nobile-Orazio, Eduardo

AU - Liberatore, Giuseppe

AU - Hiew, Fu Liong

AU - Martínez-Piñeiro, Alicia

AU - Carvajal, Alejandra

AU - Piñar-Morales, Raquel

AU - Usón-Martín, Mercedes

AU - Albertí, Olalla

AU - López-Pérez, Maria Ángeles

AU - Márquez, Fabian

AU - Pardo-Fernández, Julio

AU - Muñoz-Delgado, Laura

AU - Cabrera-Serrano, Macarena

AU - Ortiz, Nicolau

AU - Bartolomé, Manuel

AU - Duman, Özgür

AU - Bril, Vera

AU - Segura-Chávez, Darwin

AU - Pitarokoili, Kalliopi

AU - Steen, Claudia

AU - Illa, Isabel

AU - Querol, Luis

N1 - Funding Information: This work is supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain and FEDER under grant FIS19/0140 and personal grant INT20/00080, personal grant GBS-CIDP Foundation to CL, personal grant Rio Hortega CM19/00042 to LMA and the ER20P3AC7624 project of the ACCI call of the CIBERER network, Madrid, Spain. XSC was supported by a Sara Borrell postdoctoral fellowship project CD18/00195, funded by Instituto de Salud Carlos III and cofunded by European Union (ERDF/ESF, A way to make Europe/Investing in your future). A.C. thanks the Medical Research Council (MR/T001712/1), the Fondazione CARIPLO (2019-1836), the Italian Ministry of Health-Ricerca Corrente, the Inherited Neuropathy Consortium (INC) and Fondazione Regionale per la Ricerca Biomedica for grant suport Funding Information: The Article Processing Charge was funded by authors. Publisher Copyright: © American Academy of Neurology.

PY - 2022/1/2

Y1 - 2022/1/2

N2 - BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

AB - BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

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U2 - 10.1212/NXI.0000000000001098

DO - 10.1212/NXI.0000000000001098

M3 - Article

C2 - 34728497

AN - SCOPUS:85126170268

SN - 2332-7812

VL - 9

JO - Neurology(R) neuroimmunology & neuroinflammation

JF - Neurology(R) neuroimmunology & neuroinflammation

IS - 1

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Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

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