Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children

Elizabeth A. Spencer, Sonia M. Davis, David R. Mack, Brendan M. Boyle, Anne M. Griffiths, Neal S. Leleiko, Cary G. Sauer, David J. Keljo, James F. Markowitz, Susan S. Baker, Joel Rosh, Robert N. Baldassano, Maria Oliva-Hemker, Marian D. Pfefferkorn, Anthony R. Otley, Melvin B. Heyman, Joshua D. Noe, Ashish S. Patel, Paul A. Rufo, Keith Benkov & 16 others Jonathan Evans, Stephen Guthery, Michael Kappelman, Dedrick Moulton, Jennifer Strople, Boris Sudel, Prateek Wali, David Ziring, Vin Tangpricha, M. Alison Marquis, Thomas D. Walters, Margaret H. Collins, Subra Kugathasan, Lee A. Denson, Jeffrey S. Hyams, Marla C. Dubinsky

Research output: Contribution to journalArticle

Abstract

Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Original languageEnglish (US)
Pages (from-to)1335-1343
Number of pages9
JournalInflammatory bowel diseases
Volume24
Issue number6
DOIs
StatePublished - May 18 2018

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Ulcerative Colitis
Serology
Phenotype
Microbial Interactions
Leukocyte L1 Antigen Complex
Antineutrophil Cytoplasmic Antibodies
Colitis
Vitamin D
Age Groups
Demography
Pediatrics
Antigens
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Spencer, E. A., Davis, S. M., Mack, D. R., Boyle, B. M., Griffiths, A. M., Leleiko, N. S., ... Dubinsky, M. C. (2018). Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children. Inflammatory bowel diseases, 24(6), 1335-1343. https://doi.org/10.1093/ibd/izy009
Spencer, Elizabeth A. ; Davis, Sonia M. ; Mack, David R. ; Boyle, Brendan M. ; Griffiths, Anne M. ; Leleiko, Neal S. ; Sauer, Cary G. ; Keljo, David J. ; Markowitz, James F. ; Baker, Susan S. ; Rosh, Joel ; Baldassano, Robert N. ; Oliva-Hemker, Maria ; Pfefferkorn, Marian D. ; Otley, Anthony R. ; Heyman, Melvin B. ; Noe, Joshua D. ; Patel, Ashish S. ; Rufo, Paul A. ; Benkov, Keith ; Evans, Jonathan ; Guthery, Stephen ; Kappelman, Michael ; Moulton, Dedrick ; Strople, Jennifer ; Sudel, Boris ; Wali, Prateek ; Ziring, David ; Tangpricha, Vin ; Marquis, M. Alison ; Walters, Thomas D. ; Collins, Margaret H. ; Kugathasan, Subra ; Denson, Lee A. ; Hyams, Jeffrey S. ; Dubinsky, Marla C. / Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children. In: Inflammatory bowel diseases. 2018 ; Vol. 24, No. 6. pp. 1335-1343.
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abstract = "Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62{\%} less than 12 years old and 66{\%} 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19{\%}, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19{\%} and more common in younger children with 32{\%} less than 12 years old as compared with 14{\%} 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16{\%} versus 7{\%} (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.",
author = "Spencer, {Elizabeth A.} and Davis, {Sonia M.} and Mack, {David R.} and Boyle, {Brendan M.} and Griffiths, {Anne M.} and Leleiko, {Neal S.} and Sauer, {Cary G.} and Keljo, {David J.} and Markowitz, {James F.} and Baker, {Susan S.} and Joel Rosh and Baldassano, {Robert N.} and Maria Oliva-Hemker and Pfefferkorn, {Marian D.} and Otley, {Anthony R.} and Heyman, {Melvin B.} and Noe, {Joshua D.} and Patel, {Ashish S.} and Rufo, {Paul A.} and Keith Benkov and Jonathan Evans and Stephen Guthery and Michael Kappelman and Dedrick Moulton and Jennifer Strople and Boris Sudel and Prateek Wali and David Ziring and Vin Tangpricha and Marquis, {M. Alison} and Walters, {Thomas D.} and Collins, {Margaret H.} and Subra Kugathasan and Denson, {Lee A.} and Hyams, {Jeffrey S.} and Dubinsky, {Marla C.}",
year = "2018",
month = "5",
day = "18",
doi = "10.1093/ibd/izy009",
language = "English (US)",
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Spencer, EA, Davis, SM, Mack, DR, Boyle, BM, Griffiths, AM, Leleiko, NS, Sauer, CG, Keljo, DJ, Markowitz, JF, Baker, SS, Rosh, J, Baldassano, RN, Oliva-Hemker, M, Pfefferkorn, MD, Otley, AR, Heyman, MB, Noe, JD, Patel, AS, Rufo, PA, Benkov, K, Evans, J, Guthery, S, Kappelman, M, Moulton, D, Strople, J, Sudel, B, Wali, P, Ziring, D, Tangpricha, V, Marquis, MA, Walters, TD, Collins, MH, Kugathasan, S, Denson, LA, Hyams, JS & Dubinsky, MC 2018, 'Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children', Inflammatory bowel diseases, vol. 24, no. 6, pp. 1335-1343. https://doi.org/10.1093/ibd/izy009

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children. / Spencer, Elizabeth A.; Davis, Sonia M.; Mack, David R.; Boyle, Brendan M.; Griffiths, Anne M.; Leleiko, Neal S.; Sauer, Cary G.; Keljo, David J.; Markowitz, James F.; Baker, Susan S.; Rosh, Joel; Baldassano, Robert N.; Oliva-Hemker, Maria; Pfefferkorn, Marian D.; Otley, Anthony R.; Heyman, Melvin B.; Noe, Joshua D.; Patel, Ashish S.; Rufo, Paul A.; Benkov, Keith; Evans, Jonathan; Guthery, Stephen; Kappelman, Michael; Moulton, Dedrick; Strople, Jennifer; Sudel, Boris; Wali, Prateek; Ziring, David; Tangpricha, Vin; Marquis, M. Alison; Walters, Thomas D.; Collins, Margaret H.; Kugathasan, Subra; Denson, Lee A.; Hyams, Jeffrey S.; Dubinsky, Marla C.

In: Inflammatory bowel diseases, Vol. 24, No. 6, 18.05.2018, p. 1335-1343.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children

AU - Spencer, Elizabeth A.

AU - Davis, Sonia M.

AU - Mack, David R.

AU - Boyle, Brendan M.

AU - Griffiths, Anne M.

AU - Leleiko, Neal S.

AU - Sauer, Cary G.

AU - Keljo, David J.

AU - Markowitz, James F.

AU - Baker, Susan S.

AU - Rosh, Joel

AU - Baldassano, Robert N.

AU - Oliva-Hemker, Maria

AU - Pfefferkorn, Marian D.

AU - Otley, Anthony R.

AU - Heyman, Melvin B.

AU - Noe, Joshua D.

AU - Patel, Ashish S.

AU - Rufo, Paul A.

AU - Benkov, Keith

AU - Evans, Jonathan

AU - Guthery, Stephen

AU - Kappelman, Michael

AU - Moulton, Dedrick

AU - Strople, Jennifer

AU - Sudel, Boris

AU - Wali, Prateek

AU - Ziring, David

AU - Tangpricha, Vin

AU - Marquis, M. Alison

AU - Walters, Thomas D.

AU - Collins, Margaret H.

AU - Kugathasan, Subra

AU - Denson, Lee A.

AU - Hyams, Jeffrey S.

AU - Dubinsky, Marla C.

PY - 2018/5/18

Y1 - 2018/5/18

N2 - Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

AB - Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

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U2 - 10.1093/ibd/izy009

DO - 10.1093/ibd/izy009

M3 - Article

VL - 24

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JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

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Spencer EA, Davis SM, Mack DR, Boyle BM, Griffiths AM, Leleiko NS et al. Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children. Inflammatory bowel diseases. 2018 May 18;24(6):1335-1343. https://doi.org/10.1093/ibd/izy009