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Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort.
Am J Gastroenterol 2016; 111(5):733-43AJ

Abstract

OBJECTIVES

Elevated serum immunoglobulin G4 (IgG4) levels have been associated with autoimmune pancreatitis and IgG4-related disease (IgG4-RD) for over a decade. However, an elevated serum IgG4 is not specific for the disease. There have been inconsistent reports of its use in diagnosis, as a marker of disease relapse, and its relationship to organ involvement in retrospective cohorts. The aims of this study were to ascertain conditions that are associated with an elevated serum IgG4 and to investigate the role of IgG4 in diagnosis, relapse, and organ involvement in a prospective cohort of patients with IgG4-RD.

METHODS

We evaluated serum IgG4 measurements in the Oxford Immunology Laboratory over 6 years. Patients in whom serum IgG4 was requested to differentiate IgG4-RD from other diseases were recruited into a longitudinal follow-up study to determine final diagnosis. In a prospective cohort of IgG4-RD patients, organ involvement, response to therapy, and disease relapse were determined.

RESULTS

Two thousand and sixty-seven samples from 1,510 patients had serum IgG4 measured. Of these, IgG4 was elevated (≥1.4 g l(-1)) in 243 (16.1%) patients. The main indication (85.6%) was to distinguish between IgG4-RD and non-IgG4-RD conditions. Only 5.1% of patients who had serum IgG4 measured for this purpose had a final diagnosis of IgG4-RD. Of those with an elevated serum IgG4, 22.4% met IgG4-RD diagnostic criteria. Serum IgG4 was elevated in 48 (82.8%) of IgG4-RD patients. An IgG4 cutoff of 1.4 g l(-1) gave a sensitivity of 82.8% and specificity of 84.7% to diagnose IgG4-RD. Increasing this to 2.8 g l(-1) increased specificity to 96.2% and negative predictive value to 97.7%, with a lower sensitivity of 56.9% and positive predictive value of 44.5%. Serum IgG4 levels fell with corticosteroid therapy, but this was not disease-specific. A serum IgG4 of ≥2.8 g l(-1) at diagnosis was associated with multi-organ involvement and risk of relapse.

CONCLUSIONS

Serum IgG4 levels are elevated in multiple non-IgG4-RD inflammatory and malignant conditions, with less than one-quarter of those with an elevated IgG4 meeting IgG4-RD diagnostic criteria. A serum IgG4 of ≥2.8 g l(-1) is useful in distinguishing between IgG4-RD and non-IgG4-RD diagnoses, predicting multiple-organ involvement and risk of relapse in IgG4-RD.

Authors+Show Affiliations

Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Nuffield Department of Medicine, Oxford University, Oxford, UK.Clinical Immunology Department, Churchill Hospital, Oxford, UK.Clinical Immunology Department, Churchill Hospital, Oxford, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Nuffield Department of Medicine, Oxford University, Oxford, UK.Nuffield Department of Medicine, Oxford University, Oxford, UK.Histopathology Department, Southampton General Hospital, Southampton, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Gastroenterology, Horton Hospital, Banbury, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Nuffield Department of Medicine, Oxford University, Oxford, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Nuffield Department of Medicine, Oxford University, Oxford, UK.Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Nuffield Department of Medicine, Oxford University, Oxford, UK. Oxford NIHR and BRC, Oxford, UK.Clinical Immunology Department, Churchill Hospital, Oxford, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27091321

Citation

Culver, Emma L., et al. "Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort." The American Journal of Gastroenterology, vol. 111, no. 5, 2016, pp. 733-43.
Culver EL, Sadler R, Simpson D, et al. Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort. Am J Gastroenterol. 2016;111(5):733-43.
Culver, E. L., Sadler, R., Simpson, D., Cargill, T., Makuch, M., Bateman, A. C., ... Ferry, B. (2016). Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort. The American Journal of Gastroenterology, 111(5), pp. 733-43. doi:10.1038/ajg.2016.40.
Culver EL, et al. Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort. Am J Gastroenterol. 2016;111(5):733-43. PubMed PMID: 27091321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort. AU - Culver,Emma L, AU - Sadler,Ross, AU - Simpson,Dawn, AU - Cargill,Tamsin, AU - Makuch,Mateusz, AU - Bateman,Adrian C, AU - Ellis,Anthony J, AU - Collier,Jane, AU - Chapman,Roger W, AU - Klenerman,P, AU - Barnes,Eleanor, AU - Ferry,Berne, Y1 - 2016/04/19/ PY - 2015/09/01/received PY - 2016/01/02/accepted PY - 2016/4/20/entrez PY - 2016/4/20/pubmed PY - 2017/6/9/medline SP - 733 EP - 43 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 111 IS - 5 N2 - OBJECTIVES: Elevated serum immunoglobulin G4 (IgG4) levels have been associated with autoimmune pancreatitis and IgG4-related disease (IgG4-RD) for over a decade. However, an elevated serum IgG4 is not specific for the disease. There have been inconsistent reports of its use in diagnosis, as a marker of disease relapse, and its relationship to organ involvement in retrospective cohorts. The aims of this study were to ascertain conditions that are associated with an elevated serum IgG4 and to investigate the role of IgG4 in diagnosis, relapse, and organ involvement in a prospective cohort of patients with IgG4-RD. METHODS: We evaluated serum IgG4 measurements in the Oxford Immunology Laboratory over 6 years. Patients in whom serum IgG4 was requested to differentiate IgG4-RD from other diseases were recruited into a longitudinal follow-up study to determine final diagnosis. In a prospective cohort of IgG4-RD patients, organ involvement, response to therapy, and disease relapse were determined. RESULTS: Two thousand and sixty-seven samples from 1,510 patients had serum IgG4 measured. Of these, IgG4 was elevated (≥1.4 g l(-1)) in 243 (16.1%) patients. The main indication (85.6%) was to distinguish between IgG4-RD and non-IgG4-RD conditions. Only 5.1% of patients who had serum IgG4 measured for this purpose had a final diagnosis of IgG4-RD. Of those with an elevated serum IgG4, 22.4% met IgG4-RD diagnostic criteria. Serum IgG4 was elevated in 48 (82.8%) of IgG4-RD patients. An IgG4 cutoff of 1.4 g l(-1) gave a sensitivity of 82.8% and specificity of 84.7% to diagnose IgG4-RD. Increasing this to 2.8 g l(-1) increased specificity to 96.2% and negative predictive value to 97.7%, with a lower sensitivity of 56.9% and positive predictive value of 44.5%. Serum IgG4 levels fell with corticosteroid therapy, but this was not disease-specific. A serum IgG4 of ≥2.8 g l(-1) at diagnosis was associated with multi-organ involvement and risk of relapse. CONCLUSIONS: Serum IgG4 levels are elevated in multiple non-IgG4-RD inflammatory and malignant conditions, with less than one-quarter of those with an elevated IgG4 meeting IgG4-RD diagnostic criteria. A serum IgG4 of ≥2.8 g l(-1) is useful in distinguishing between IgG4-RD and non-IgG4-RD diagnoses, predicting multiple-organ involvement and risk of relapse in IgG4-RD. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/27091321/Elevated_Serum_IgG4_Levels_in_Diagnosis_Treatment_Response_Organ_Involvement_and_Relapse_in_a_Prospective_IgG4_Related_Disease_UK_Cohort_ L2 - http://Insights.ovid.com/pubmed?pmid=27091321 DB - PRIME DP - Unbound Medicine ER -