Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features

Matthew A. Sherman; Rose Graf; Sara E. Sabbagh; Angeles S. Galindo-Feria; Iago Pinal-Fernandez; Katherine Pak; Takayuki Kishi; Willy A. Flegel; Ira N. Targoff; Frederick W. Miller; Ingrid E. Lundberg; Lisa G. Rider; Andrew L. Mammen; Daniel A. Albert; Bita Arabshahi; Imelda M. Balboni; Susan Ballinger; Lilliana Barillas-Arias; Mara L. Becker; C. April Bingham; John F. Bohnsack; Ruy Carrasco; Victoria W. Cartwright; Randy Q. Cron; Rodolfo Curiel; Jason A. Dare; Wendy De La Pena; Marietta M. Deguzman; B. Anne Eberhard; Barbara S. Edelheit; Terri H. Finkel; Stephen W. George; Harry L. Gewanter; Ellen A. Goldmuntz; Brandt P. Groh; Hillary H. Haftel; William P. Hannan; Michael Henrickson; Gloria C. Higgins; Patricia M. Hobday; Russell J. Hopp; Adam M. Huber; Lisa Imundo; C. J. Inman; Anna Jansen; James Jarvis; Olcay Y. Jones; Ankur Kamdar; Hanna Kim; Daniel J. Kingsbury; Carol B. Lindsley; Gulnara Mamyrova; Paul L. McCarthy; Stephen R. Mitchell; Frederick T. Murphy; Kabita Nanda; Terrance O'Hanlon; Elif A. Oral; Lauren M. Pachman; Maria D. Perez; Donald A. Person; C. Egla Rabinovich; Tova Ronis; Adam Schiffenbauer; Bracha Shaham; Sara H. Sinal; Jennifer Soep; Matthew L. Stoll; Sangeeta Sule; Stacey Tarvin; Scott A. Vogelgesang; Rita Volochayev; Jennifer C. Wargula; Patience H. White

doi:10.1093/rheumatology/keac428

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features

Matthew A. Sherman, Rose Graf, Sara E. Sabbagh, Angeles S. Galindo-Feria, Iago Pinal-Fernandez, Katherine Pak, Takayuki Kishi, Willy A. Flegel, Ira N. Targoff, Frederick W. Miller, Ingrid E. Lundberg, Lisa G. Rider, Andrew L. Mammen^*, Daniel A. Albert, Bita Arabshahi, Imelda M. Balboni, Susan Ballinger, Lilliana Barillas-Arias, Mara L. Becker, C. April BinghamJohn F. Bohnsack, Ruy Carrasco, Victoria W. Cartwright, Randy Q. Cron, Rodolfo Curiel, Jason A. Dare, Wendy De La Pena, Marietta M. Deguzman, B. Anne Eberhard, Barbara S. Edelheit, Terri H. Finkel, Stephen W. George, Harry L. Gewanter, Ellen A. Goldmuntz, Brandt P. Groh, Hillary H. Haftel, William P. Hannan, Michael Henrickson, Gloria C. Higgins, Patricia M. Hobday, Russell J. Hopp, Adam M. Huber, Lisa Imundo, C. J. Inman, Anna Jansen, James Jarvis, Olcay Y. Jones, Ankur Kamdar, Hanna Kim, Daniel J. Kingsbury, Carol B. Lindsley, Gulnara Mamyrova, Paul L. McCarthy, Stephen R. Mitchell, Frederick T. Murphy, Kabita Nanda, Terrance O'Hanlon, Elif A. Oral, Lauren M. Pachman, Maria D. Perez, Donald A. Person, C. Egla Rabinovich, Tova Ronis, Adam Schiffenbauer, Bracha Shaham, Sara H. Sinal, Jennifer Soep, Matthew L. Stoll, Sangeeta Sule, Stacey Tarvin, Scott A. Vogelgesang, Rita Volochayev, Jennifer C. Wargula, Patience H. White

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods: Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results: Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion: Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.

Original language	English (US)
Pages (from-to)	SI226-SI234
Journal	Rheumatology (United Kingdom)
Volume	62
Issue number	SI2
DOIs	https://doi.org/10.1093/rheumatology/keac428
State	Published - Feb 1 2023

Funding

This research was supported by the Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIA AR041203), National Institute of Environmental Health Sciences (ZIA ES101074, ZIA ES101081) and the Clinical Center (ZIC CL002128) of the National Institutes of Health. S.E.S. and T.K. were partially supported by the Cure JM Foundation. I.E.L. is supported by the Swedish Research Council (Vetenskapsradet; 2020-01378), King Gustaf V 80-year Foundation (Stiftelsen Konung Gustaf V; s 80-arsfond), Swedish Rheumatism Association (Reumatikerforbundet) and Stockholm Region Council (ALF project). G.M. has received grants/research support from the Cure JM Foundation

Keywords

FHL1 autoantibodies
juvenile idiopathic inflammatory myopathies
myositis
myositis-associated autoantibodies

ASJC Scopus subject areas

Rheumatology
Pharmacology (medical)

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10.1093/rheumatology/keac428

Cite this

Sherman, M. A., Graf, R., Sabbagh, S. E., Galindo-Feria, A. S., Pinal-Fernandez, I., Pak, K., Kishi, T., Flegel, W. A., Targoff, I. N., Miller, F. W., Lundberg, I. E., Rider, L. G., Mammen, A. L., Albert, D. A., Arabshahi, B., Balboni, I. M., Ballinger, S., Barillas-Arias, L., Becker, M. L., ... White, P. H. (2023). Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features. Rheumatology (United Kingdom), 62(SI2), SI226-SI234. https://doi.org/10.1093/rheumatology/keac428

@article{edb8dc31a26b4dbc921194dafd35e17e,

title = "Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features",

abstract = "Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods: Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results: Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion: Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.",

keywords = "FHL1 autoantibodies, juvenile idiopathic inflammatory myopathies, myositis, myositis-associated autoantibodies",

author = "Sherman, {Matthew A.} and Rose Graf and Sabbagh, {Sara E.} and Galindo-Feria, {Angeles S.} and Iago Pinal-Fernandez and Katherine Pak and Takayuki Kishi and Flegel, {Willy A.} and Targoff, {Ira N.} and Miller, {Frederick W.} and Lundberg, {Ingrid E.} and Rider, {Lisa G.} and Mammen, {Andrew L.} and Albert, {Daniel A.} and Bita Arabshahi and Balboni, {Imelda M.} and Susan Ballinger and Lilliana Barillas-Arias and Becker, {Mara L.} and Bingham, {C. April} and Bohnsack, {John F.} and Ruy Carrasco and Cartwright, {Victoria W.} and Cron, {Randy Q.} and Rodolfo Curiel and Dare, {Jason A.} and {De La Pena}, Wendy and Deguzman, {Marietta M.} and Eberhard, {B. Anne} and Edelheit, {Barbara S.} and Finkel, {Terri H.} and George, {Stephen W.} and Gewanter, {Harry L.} and Goldmuntz, {Ellen A.} and Groh, {Brandt P.} and Haftel, {Hillary H.} and Hannan, {William P.} and Michael Henrickson and Higgins, {Gloria C.} and Hobday, {Patricia M.} and Hopp, {Russell J.} and Huber, {Adam M.} and Lisa Imundo and Inman, {C. J.} and Anna Jansen and James Jarvis and Jones, {Olcay Y.} and Ankur Kamdar and Hanna Kim and Kingsbury, {Daniel J.} and Lindsley, {Carol B.} and Gulnara Mamyrova and McCarthy, {Paul L.} and Mitchell, {Stephen R.} and Murphy, {Frederick T.} and Kabita Nanda and Terrance O'Hanlon and Oral, {Elif A.} and Pachman, {Lauren M.} and Perez, {Maria D.} and Person, {Donald A.} and Rabinovich, {C. Egla} and Tova Ronis and Adam Schiffenbauer and Bracha Shaham and Sinal, {Sara H.} and Jennifer Soep and Stoll, {Matthew L.} and Sangeeta Sule and Stacey Tarvin and Vogelgesang, {Scott A.} and Rita Volochayev and Wargula, {Jennifer C.} and White, {Patience H.}",

note = "Publisher Copyright: {\textcopyright} 2022 Published by Oxford University Press on behalf of the British Society for Rheumatology.",

year = "2023",

month = feb,

day = "1",

doi = "10.1093/rheumatology/keac428",

language = "English (US)",

volume = "62",

pages = "SI226--SI234",

journal = "Rheumatology (United Kingdom)",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "SI2",

}

Sherman, MA, Graf, R, Sabbagh, SE, Galindo-Feria, AS, Pinal-Fernandez, I, Pak, K, Kishi, T, Flegel, WA, Targoff, IN, Miller, FW, Lundberg, IE, Rider, LG, Mammen, AL, Albert, DA, Arabshahi, B, Balboni, IM, Ballinger, S, Barillas-Arias, L, Becker, ML, Bingham, CA, Bohnsack, JF, Carrasco, R, Cartwright, VW, Cron, RQ, Curiel, R, Dare, JA, De La Pena, W, Deguzman, MM, Eberhard, BA, Edelheit, BS, Finkel, TH, George, SW, Gewanter, HL, Goldmuntz, EA, Groh, BP, Haftel, HH, Hannan, WP, Henrickson, M, Higgins, GC, Hobday, PM, Hopp, RJ, Huber, AM, Imundo, L, Inman, CJ, Jansen, A, Jarvis, J, Jones, OY, Kamdar, A, Kim, H, Kingsbury, DJ, Lindsley, CB, Mamyrova, G, McCarthy, PL, Mitchell, SR, Murphy, FT, Nanda, K, O'Hanlon, T, Oral, EA, Pachman, LM, Perez, MD, Person, DA, Rabinovich, CE, Ronis, T, Schiffenbauer, A, Shaham, B, Sinal, SH, Soep, J, Stoll, ML, Sule, S, Tarvin, S, Vogelgesang, SA, Volochayev, R, Wargula, JC & White, PH 2023, 'Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features', Rheumatology (United Kingdom), vol. 62, no. SI2, pp. SI226-SI234. https://doi.org/10.1093/rheumatology/keac428

TY - JOUR

T1 - Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features

AU - Sherman, Matthew A.

AU - Graf, Rose

AU - Sabbagh, Sara E.

AU - Galindo-Feria, Angeles S.

AU - Pinal-Fernandez, Iago

AU - Pak, Katherine

AU - Kishi, Takayuki

AU - Flegel, Willy A.

AU - Targoff, Ira N.

AU - Miller, Frederick W.

AU - Lundberg, Ingrid E.

AU - Rider, Lisa G.

AU - Mammen, Andrew L.

AU - Albert, Daniel A.

AU - Arabshahi, Bita

AU - Balboni, Imelda M.

AU - Ballinger, Susan

AU - Barillas-Arias, Lilliana

AU - Becker, Mara L.

AU - Bingham, C. April

AU - Bohnsack, John F.

AU - Carrasco, Ruy

AU - Cartwright, Victoria W.

AU - Cron, Randy Q.

AU - Curiel, Rodolfo

AU - Dare, Jason A.

AU - De La Pena, Wendy

AU - Deguzman, Marietta M.

AU - Eberhard, B. Anne

AU - Edelheit, Barbara S.

AU - Finkel, Terri H.

AU - George, Stephen W.

AU - Gewanter, Harry L.

AU - Goldmuntz, Ellen A.

AU - Groh, Brandt P.

AU - Haftel, Hillary H.

AU - Hannan, William P.

AU - Henrickson, Michael

AU - Higgins, Gloria C.

AU - Hobday, Patricia M.

AU - Hopp, Russell J.

AU - Huber, Adam M.

AU - Imundo, Lisa

AU - Inman, C. J.

AU - Jansen, Anna

AU - Jarvis, James

AU - Jones, Olcay Y.

AU - Kamdar, Ankur

AU - Kim, Hanna

AU - Kingsbury, Daniel J.

AU - Lindsley, Carol B.

AU - Mamyrova, Gulnara

AU - McCarthy, Paul L.

AU - Mitchell, Stephen R.

AU - Murphy, Frederick T.

AU - Nanda, Kabita

AU - O'Hanlon, Terrance

AU - Oral, Elif A.

AU - Pachman, Lauren M.

AU - Perez, Maria D.

AU - Person, Donald A.

AU - Rabinovich, C. Egla

AU - Ronis, Tova

AU - Schiffenbauer, Adam

AU - Shaham, Bracha

AU - Sinal, Sara H.

AU - Soep, Jennifer

AU - Stoll, Matthew L.

AU - Sule, Sangeeta

AU - Tarvin, Stacey

AU - Vogelgesang, Scott A.

AU - Volochayev, Rita

AU - Wargula, Jennifer C.

AU - White, Patience H.

PY - 2023/2/1

Y1 - 2023/2/1

N2 - Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods: Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results: Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion: Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.

AB - Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Methods: Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Results: Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Conclusion: Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.

KW - FHL1 autoantibodies

KW - juvenile idiopathic inflammatory myopathies

KW - myositis

KW - myositis-associated autoantibodies

UR - http://www.scopus.com/inward/record.url?scp=85160024916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85160024916&partnerID=8YFLogxK

U2 - 10.1093/rheumatology/keac428

DO - 10.1093/rheumatology/keac428

M3 - Article

C2 - 35961028

AN - SCOPUS:85160024916

SN - 1462-0324

VL - 62

SP - SI226-SI234

JO - Rheumatology (United Kingdom)

JF - Rheumatology (United Kingdom)

IS - SI2

ER -

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features

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