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IgG4 is an immunoglobulin G subclass of antibody. Mouse monoclonal IgG4 [HP6025] is specific for the Fc region of human IgG4. IgG4 can be helpful in the diagnosis of IgG4 related systemic disease (IgG4-RSD). IgG4-RSD, also known as IgG4-related sclerosing disease, can be found in many different organs and presents itself with such symptoms as lymphoplasmacytic infiltration, mass formation, sclerosis, obliterative phlebitis and increased expression of IgG4+ plasma cells as well as a high IgG4+/IgG+ ratio, typically >30% (1-4).
IgG4 has been shown to be overexpressed in inflammatory pseudotumor (IPT) and under expressed in inflammatory myofibroblastic tumor (IMT). IgG4 may be a useful differential marker in a panel with IgG (IgG4+/ IgG+ plasma cell ratio is higher in IPT) and ALK (positive in IMT) (4,5).
In pulmonary nodular lymphoid hyperplasia (PNLH), there are an increased number of IgG4+ plasma cells as well as a higher ratio of IgG4+ to IgG+ plasma cells as compared to other pulmonary lymphoid proliferations. These characteristics may aid in distinguishing PNLH from low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT) (6).
Fc region of human IgG4
1. Khosroshahi A, et al. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol. 2011 Jan; 23(1):57-66.
2. Divatia M, Kim S, Ro J. IgG4-related sclerosing disease, an emerging entity: a review of a multi-system disease. Yonsei Med J. 2012 Jan; 53(1):15-34.
3. Sato Y, et al. Clinicopathologic analysis of IgG4-related skin disease. Mod Pathol. 2013 Apr; 26(4):523-32.
4. Saab ST, et al. IgG4 plasma cells in inflammatory myofibroblastic tumor: inflammatory marker or pathogenic link? Mod Pathol. 2011 Apr; 24(4):606-12.
5. Bhagat P, et al. Pulmonary inflammatory myofibroblastic tumor and IgG4-related inflammatory pseudotumor: a diagnostic dilemma. Virchows Arch. 2013 Dec; 463 (6):743-7.
6. Guinee DG Jr, et al. Pulmonary nodular lymphoid hyperplasia (pulmonary pseudolymphoma): the significance of increased numbers of IgG4-positive plasma cells. Am J Surg Pathol. 2010 Dec; 34(12):1812-9.
7. Brenner I, et al. Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression. Mod Pathol. 2013 Dec; 26(12):1568-76. 8. Sepehr A, et al. IgG4+ to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other “mass forming” pancreatic lesions. Am J Surg Pathol. 2008 Dec; 32(12):1770-9.
9. Hamilton RG, et al. Epitope mapping of human immunoglobulin-specific murine monoclonal antibodies with domain-switched, deleted and point-mutated chimeric antibodies. J Immunol Methods. 1993 Jan 14; 158(1):107-22.
10. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
11. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.