Circulating IgG4⁺ Plasmablast Count as a Diagnostic Tool in Autoimmune Pancreatitis

Type 1 autoimmune pancreatitis (AIP) is an IgG4-related disease whose diagnosis is challenging. The aim of this study was to investigate the diagnostic value of circulating total and IgG4⁺ plasmablasts in differentiating this condition from the other main pancreatic diseases.

Patients with type 1 AIP (n = 19) were prospectively enrolled in a tertiary center together with patients suffering from type 2 or not otherwise specified (NOS) AIP (n = 10), pancreatic adenocarcinoma (n = 17), chronic pancreatitis (n = 20), and intraductal papillary mucinous neoplasia or chronic asymptomatic pancreatic hyperenzymemia (n = 21) as control groups. Flow cytometry was used to measure the total plasmablast and IgG4⁺ plasmablast number by gating peripheral blood CD45⁺CD19⁺CD38^hiCD20^-CD24^-CD27⁺ and CD45⁺CD19⁺CD38^hiCD20^-CD24^-CD27⁺IgG4⁺ cells, respectively. In patients with AIP, these cell populations were also evaluated after 1 month of therapy, after 2-4 months from the end of treatment, and after 1 year from the enrollment. The study was approved by the local ethics committee (protocol number: 59133, 30/11/2017).

Total plasmablast quantification was capable of discriminating type 1 AIP from all the other pancreatic disorders with a sensitivity of 47% and a specificity of 81%, according to a cutoff of 4500 cells/mL (AUC = 0.738), whereas IgG4⁺ plasmablast count distinguished type 1 AIP from all the other pancreatic disorders with a sensitivity of 80% and a specificity of 97% when applying a cutoff of 210 IgG4⁺ cells/mL (AUC = 0.879). The basal IgG4⁺ plasmablast number was significantly higher (P = .0001) in type 1 AIP than in type 2/NOS AIP, decreased after steroid therapy, and increased at disease relapse.

IgG4⁺ plasmablast count represents a potentially useful biomarker to differentiate type 1 from type 2/NOS AIP and from other pancreatic diseases.