Background/Purpose:

IgG4-delated disease (IgG4-RD) is an immune-mediate condition responsible for inflammatory lesions that can affect nearly every organ.  Diagnosis is challenging as it relies upon classic histopathology and immunohistochemical findings as well as careful pathology interpretation and clinicopathologic correlation.  No single finding, including the IgG4+ plasma cell infiltrate or the serum IgG4 concentration, is diagnostic.  Paramount is the ability to distinguish IgG4-RD from clinically similar conditions such as malignancies.  A biomarker to identify patients with active disease would improve diagnosis and may help distinguish subtypes.  Here we describe the clinical characteristics of patients with active, untreated IgG4-RD and an elevated IgG4+ plasmablast level. 

Methods:

This study was approved by the institutional review board and all subjects provided informed, written consent. All patients had histopathologic proof and clinical features consistent with their IgG4-RD diagnoses. Nineteen IgG4-RD patients with active, untreated disease were evaluated and their blood sample findings were compared with those of ten healthy controls.  Patients’ disease activity was scored by the IgG4-RD Responder Index (RI) where an RI>/= 3 is regarded as active disease. Flow cytometry was used to measure absolute plasmablast count per ml by gating peripheral blood for IgG4⁺, CD19^lowCD20^–CD38⁺CD27⁺.  Serum IgG4 levels were measured by nephelometry. Student’s t-tests were used to compare the groups.

Results:

The mean age of the IgG4-RD group was 58 years (range: 41-77 years) and 14 (74%) were male.  Nine of the IgG4-RD patients had at least 3 organs involved; the remainder had active IgG4-RD in only 1 or 2 organs.  The mean IgG4-RD RI was 11.2 (range: 3-36).  The mean ages of the healthy controls was 42.5 years, six of whom were males. All of the IgG4-RD patients had an elevated IgG4+ plasmablast concentrations (normal <500 /ml; mean: 14,316 /ml; range: 732-85,208 /ml).  In contrast, the mean plasmablast concentration among healthy controls was 63/ml (range: 1-156/ml; p=0.02).  Among IgG4-RD patients, eight (42%) had normal serum IgG4 concentrations (nl< 135mg/dL; mean: 58.3 mg/dL; range: 5.3-123 mg/dL). The mean IgG4+ plasmablast concentration did not differ significantly according to the presence or absence of an elevated serum IgG4 concentration (means =14,249/ml & 13,169/ml, respectively; p=0.94).  Patients with a normal serum IgG4 concentration were more likely to have single organ disease as well as lower inflammatory markers; in contrast, patients with an elevated serum IgG4 concentration were more likely to have 3 or more organs involved (64% vs. 25%, p=0.10) and abnormal inflammatory markers (p<0.05 for C3 & CRP; p=0.15 for ESR & C4).  The serum plasmablast concentration correlated with the number of organs affected by IgG4-RD (R²= 0.80). 

Conclusion:

IgG4-RD appears to be associated with an elevated blood concentration of IgG4+ plasmablasts.  This finding may be highly specific for IgG4-RD and may be superior in sensitivity to the serum IgG4.  Further investigations of serum IgG4+ plasmablast concentrations in IgG4-RD and other immune mediated conditions are appropriate.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-igg4-plasmablasts-in-patients-with-active-untreated-igg4-related-disease/