Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels

Sonmoon Mohapatra, Paris Charilaou, Ayush Sharma, Dhruv Pratap Singh, Raghuwansh P. Sah, David Murray, Shounak Majumder, Mark D. Topazian, Suresh T. Chari

Research output: Contribution to journalArticle

Abstract

Objectives: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). Methods: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. Results: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively. Conclusion: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.

Original languageEnglish (US)
JournalPancreatology
DOIs
StateAccepted/In press - Jan 1 2019

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Eosinophilia
Immunoglobulin G
Serum
Area Under Curve
Electronic Health Records

Keywords

  • Autoimmune pancreatitis
  • IgG4-related disease
  • IgG4-related pancreatobiliary disease
  • Peripheral eosinophilia
  • Serum IgG4 level

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

Cite this

Mohapatra, S., Charilaou, P., Sharma, A., Singh, D. P., Sah, R. P., Murray, D., ... Chari, S. T. (Accepted/In press). Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels. Pancreatology. https://doi.org/10.1016/j.pan.2019.11.016

Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels. / Mohapatra, Sonmoon; Charilaou, Paris; Sharma, Ayush; Singh, Dhruv Pratap; Sah, Raghuwansh P.; Murray, David; Majumder, Shounak; Topazian, Mark D.; Chari, Suresh T.

In: Pancreatology, 01.01.2019.

Research output: Contribution to journalArticle

Mohapatra, Sonmoon ; Charilaou, Paris ; Sharma, Ayush ; Singh, Dhruv Pratap ; Sah, Raghuwansh P. ; Murray, David ; Majumder, Shounak ; Topazian, Mark D. ; Chari, Suresh T. / Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels. In: Pancreatology. 2019.
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title = "Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels",
abstract = "Objectives: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). Methods: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. Results: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5{\%}) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2{\%} vs. n = 23/258, 8.9{\%}; p < 0.001), ≥2X (n = 23/64, 35.9{\%} vs. n = 5/54,9.3{\%}; p = 0.001) and ≥3X (n = 18/42, 42.9{\%} vs. n = 0/9, 0{\%}; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2{\%} vs. 65.9{\%}) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95{\%} CI:2.51–9.54), 3.78 (95{\%} CI:2.27–6.28), 2.78 (95{\%} CI:1.55–4.97), and 1.03 (95{\%} CI:1.02–1.05), respectively. Conclusion: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30{\%}) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.",
keywords = "Autoimmune pancreatitis, IgG4-related disease, IgG4-related pancreatobiliary disease, Peripheral eosinophilia, Serum IgG4 level",
author = "Sonmoon Mohapatra and Paris Charilaou and Ayush Sharma and Singh, {Dhruv Pratap} and Sah, {Raghuwansh P.} and David Murray and Shounak Majumder and Topazian, {Mark D.} and Chari, {Suresh T.}",
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T1 - Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels

AU - Mohapatra, Sonmoon

AU - Charilaou, Paris

AU - Sharma, Ayush

AU - Singh, Dhruv Pratap

AU - Sah, Raghuwansh P.

AU - Murray, David

AU - Majumder, Shounak

AU - Topazian, Mark D.

AU - Chari, Suresh T.

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N2 - Objectives: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). Methods: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. Results: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively. Conclusion: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.

AB - Objectives: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). Methods: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. Results: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively. Conclusion: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.

KW - Autoimmune pancreatitis

KW - IgG4-related disease

KW - IgG4-related pancreatobiliary disease

KW - Peripheral eosinophilia

KW - Serum IgG4 level

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