Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease

Khosroshahi, Arezou; Cheryk, Lynn A.; Carruthers, Mollie; Edwards, Judith A.; Bloch, Donald B.; Stone, John H.

doi:10.1002/art.38193

Cited by 110 publications

(65 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Falsely low measurements of serum IgG4 concentrations were reported in 26% of patients in 1 study because of the prozone effect. 15 This error in measurement can be circumvented by performing appropriate dilutions, which allow for the reagent antibody to remain in excess of the antigen of interest. Newer assays designed to detect higher serum IgG4 concentrations have the potential to prevent this problem in the future.…”

Section: Serum Igg4 Levelsmentioning

confidence: 99%

Diagnostic Approach to the Complexity of IgG4-Related Disease

Stone

Brito-Zerón

Bosch

et al. 2015

Mayo Clinic Proceedings

Self Cite

154

224

View full text Add to dashboard Cite

IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.

show abstract

Section: Serum Igg4 Levelsmentioning

confidence: 99%

Diagnostic Approach to the Complexity of IgG4-Related Disease

Stone

Brito-Zerón

Bosch

et al. 2015

Mayo Clinic Proceedings

Self Cite

154

224

View full text Add to dashboard Cite

show abstract

“…For patients with multiple serum Ig measurements, the fi rst serum IgG4 level recorded was used. Th e prozone eff ect (falsely low serum IgG4 values) was accounted for using serial dilutions where necessary ( 19 ).…”

Section: Disease Controlsmentioning

confidence: 99%

Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

Culver

Sadler

Simpson

et al. 2016

American Journal of Gastroenterology

188

102

View full text Add to dashboard Cite

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 specifi c 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 fi nal 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 SUPPLEMENTARY MATERIAL is linked to the online version of the paper at

show abstract

“…16 One contributing factor to the poor sensitivity of serum IgG4 is some patients with markedly elevated levels will have a falsely negative level owing to the prozone (or hook) effect. 17 The serum of case no. 3 was evaluated with a dilution assay to ensure that the serum IgG4 was truly negative.…”

Section: Modern Pathology (2015) 28 238-247mentioning

confidence: 99%

Lymphoplasmacytic sclerosing pancreatitis without IgG4 tissue infiltration or serum IgG4 elevation: IgG4-related disease without IgG4

2015

View full text Add to dashboard Cite

Type 1 autoimmune pancreatitis can be diagnosed by and is synonymous with its pathognomonic histopathologic appearance called lymphoplasmacytic sclerosing pancreatitis. Type 1 autoimmune pancreatitis, also called IgG4-related pancreatitis, is the pancreatic manifestation of IgG4-related disease. However, the role of IgG4 in the pathogenesis of IgG4-related disease is unclear. We describe patients with LPSP without serum or tissue IgG4 abnormalities. From the Mayo Clinic database of autoimmune pancreatitis patients, we identified three patients with histologically confirmed type 1 autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis) who had normal serum IgG4 and no increase in IgG4-positive plasma cells in tissue. We reviewed original clinical records and pathologic specimens, and describe the clinical and histologic features of these three patients. All patients (age/gender: 63/F, 70/M and 68/M) had normal serum IgG and IgG4 levels, and multiple sections of pancreatic histology did not show increased IgG4-positive plasma cells. Two patients were diagnosed retrospectively following pancreatic surgery, one relapsed in another organ and one has remained relapse free. Another patient was diagnosed by pancreatic core biopsy and has suffered multiple relapses that have been controlled by rituximab. These cases highlight the fact that although the currently agreed upon name for type 1 autoimmune pancreatitis is IgG4-related pancreatitis, serum and tissue IgG4 abnormalities are best considered characteristic, but not essential for the diagnosis of this enigmatic condition.

show abstract

Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease

Cited by 110 publications

References 23 publications

Diagnostic Approach to the Complexity of IgG4-Related Disease

Diagnostic Approach to the Complexity of IgG4-Related Disease

Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

Lymphoplasmacytic sclerosing pancreatitis without IgG4 tissue infiltration or serum IgG4 elevation: IgG4-related disease without IgG4

Contact Info

Product

Resources

About