Plasmablast Detection From IgG4-Related Disease Patients

IgG4-related disease (IgG4-RD) is an immune-mediated, fibro-inflammatory disease that leads to tissue damage, organ dysfunction and, if untreated, to organ failure. The disease can affect almost any anatomic location, but the sites involved most commonly are the pancreas, salivary glands, orbital adnexa, lymph nodes, and retroperitoneum. IgG4-RD, typically diagnosed among individuals who are middle-aged, is characterized by a male predominance except with regard to organs of the head and neck (e.g., the salivary glands and orbits), where the gender distribution is approximately equal. The epidemiology of IgG4-RD remains poorly understood because of its recognition only recently as a multi-organ disease. However, IgG4-RD accounts for many conditions once regarded as disparate, single-organ disorders.

The current gold standard for the diagnosis of IgG4-RD is the identification of characteristic histology and immunohistochemistry features through biopsy. These pathology features are consistent across the full range of organs affected by IgG4-RD. However, histopathologic variation can occur according to the stage of the lesion; that is, longstanding disease may be predominately fibrotic and a cellular. Confirming the diagnosis of IgG4-RD in such cases can be difficult. Moreover, IgG4-RD organ pathology and IgG4-RD mimickers, such as granulomatosis with polyangiitis (formerly Wegener's), sarcoidosis, histiocytosis, and malignancies (e.g., lymphoma and adenocarcinoma of the pancreas), may share similar features including an IgG4-positive plasma cell infiltrate. Reliance upon serum IgG4 concentrations to diagnose IgG4-RD is similarly problematic because both the specificity and positive predictive value of serum IgG4 concentrations are poor.

Plasmablasts, derived from the B-cell lineage and characterized as CD19lowCD20-CD38+CD27+, comprise a stage intermediate between activated B-cells and plasma cells. Plasmablasts are generally rare in the peripheral blood of healthy individuals, but expansions are observed briefly during responses to infection or vaccination. In contrast, in the setting of autoimmunity and persistent self-antigen(s), plasmablasts can circulate for prolonged periods.

Circulating plasmablasts have been described previously in inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple myeloma. Recently, several studies identified plasmablsts in IgG4-RD both as a diagnostic tool and as an indicator of response to treatment

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