Immunoglobulin Subclass IgG4, Serum
Supporting the diagnosis of IgG4-related disease
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The most abundant immunoglobulin isotype in human serum is immunoglobulin G (IgG). IgG immunoglobulins are comprised of 4 subclasses designated IgG1 through IgG4. Of total IgG, approximately 65% is IgG1, 25% is IgG2, 6% is IgG3, and 4% is IgG4. Each IgG subclass contains structurally unique portions of the constant region of the gamma heavy chain.
IgG subclass 4-related disease is a recently recognized syndrome of unknown etiology most often occurring in middle-aged and older men. Several organ systems can be involved and encompasses many previous and newly described diseases such as type1 autoimmune pancreatitis; Mikulicz disease and sclerosing sialadenitis; inflammatory orbital psuedotumor; chronic sclerosing aortitis; Riedel thyroiditis, a subset of Hashimoto thyroiditis; IgG4-related interstitial pneumonitis; and IgG4-related tubulointerstitial nephritis. Each of these entities is characterized by tumorlike swelling of the involved organs with infiltrative, predominately IgG4-positive, plasma cells with accompanying "storiform" fibrosis. In addition, elevated serum concentrations of IgG4 are found in 60% to 70% of patients diagnosed with IgG4-related disease.
The diagnosis of IgG4-related disease requires a tissue biopsy of the affected organ demonstrating the aforementioned histological features. It is recommended that patients suspected of having an IgG4-related disease have their serum IgG4 level measured.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-<5 months: < or =19.8 mg/dL
5-<9 months: < or =20.8 mg/dL
9-<15 months: < or =22.0 mg/dL
15-<24 months: < or =23.0 mg/dL
2-<4 years: 0.4-49.1 mg/dL
4-<7 years: 0.8-81.9 mg/dL
7-<10 years: 1.0-108.7 mg/dL
10-<13 years: 1.0-121.9 mg/dL
13-<16 years: 0.7-121.7 mg/dL
16-<18 years: 0.3-111.0 mg/dL
> or =18 years: 2.4-121.0 mg/dL
Elevated levels of IgG4 are consistent with, but not diagnostic of, IgG4-related disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Elevations in serum IgG4 concentrations are not specific to IgG4-related disease; they are also found in disorders such as multicentric Castleman disease, allergic disorders, Churg-Strauss syndrome, sarcoidosis, and a large number of other conditions.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Cheuk W, Chan JKC: IgG4-related Sclerosing Disease: A Critical Appraisal of an Evolving Clinicopathologic Entity. Adv Anat Pathol 2010;17(5):303-332
2. Zen Y, Nakanuma Y: IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol 2010;34(12):1812-1819
3. Bateman AC, Deheragoda MG: IgG4-related systemic sclerosing disease-an emerging and under-diagnosed condition. Histopathology 2009;55(4):373-383