Tissue IgG2/IgG4 Ratio as an Additional Tool to Distinguish IgG4-Related Disease From Other Fibroinflammatory Disorders

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Abstract

Interpretation of biopsies taken on suspicion of immunoglobulin (Ig)G4-related disease (IgG4-RD) may be hampered by uninterpretable immunohistochemical stains for IgG because of strong background signals. This study aims to determine the significance of tissue IgG2 positive plasma cell counts in IgG4-RD in comparison with non-IgG4-related inflammatory disorders. Descriptive, retrospective case-control study of 16 patients with IgG4-related orbital disease (IgG4-ROD) and 24 with extraorbital IgG4-RD. Histopathology and serology of this group was compared with 16 patients with orbital non-IgG4-related disorders and 22 patients with extraorbital non-IgG4-related disorders. The mean tissue IgG2/IgG4 ratio was 0.16 in IgG4-ROD and 0.27 in extraorbital IgG4-RD and far below 1 in 98% of patients. This was significantly lower compared with the non-IgG4-related disorders that showed a mean tissue IgG2/IgG4 ratio of 1.98 in the orbital and 2.20 in the extraorbital group (range: 0.20 to 10, P<0.05). In 74% of tissue samples an IgG2/IgG4 ratio >1 was seen. The tissue IgG2/IgG ratio was significantly lower in IgG4-RD compared with non-IgG4-related inflammatory disorders. Serum IgG2 concentration was not abnormal in patients with IgG4-RD. A significantly lower tissue IgG2/IgG4 and IgG2/IgG ratio was observed in IgG4-RD, compared with non-IgG4-related inflammatory disorders. Additional immunohistochemical staining for IgG2 positive plasma cells can be helpful in the diagnosis of IgG4-RD. Especially in cases with uninterpretable IgG staining, a well-recognized problem that may give rise to a failed interpretation of the biopsy.

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Detiger, S. E., Paridaens, D., Van Hagen, M., Karim, F., Van Laar, J. A. M., & Verdijk, R. M. (2022). Tissue IgG2/IgG4 Ratio as an Additional Tool to Distinguish IgG4-Related Disease From Other Fibroinflammatory Disorders. Applied Immunohistochemistry and Molecular Morphology, 30(7), 517–525. https://doi.org/10.1097/PAI.0000000000001040

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