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Ann Rheum Dis. 2015 Jan;74(1):190-5. doi: 10.1136/annrheumdis-2014-205233. Epub 2014 May 9.

Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations.

Author information

1
Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
2
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
3
Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
4
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVES:

We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD).

MATERIALS METHODS:

We evaluated patients with active, untreated, biopsy-proven IgG4-RD affecting various organs. Flow cytometry was used to measure total plasmablast and IgG4+ plasmablast counts by gating peripheral blood for CD19lowCD38+CD20-CD27+ cells and CD19lowCD38+CD20-CD27+IgG4+ cells. Serum IgG4 concentrations were measured by nephelometry. We compared 37 IgG4-RD patients to 35 controls, including healthy individuals (n=14) and patients with other inflammatory diseases before treatment (n=21).

RESULTS:

The IgG4-RD patients' mean age was 59, and 68% were male. Fourteen patients (38%) had three or more organs involved. The IgG4-RD patients had substantially elevated total plasmablast counts (median 4698/mL, range 610-79524/mL) compared to both untreated disease controls (median 592/mL, range 19-4294/mL; p < 0.001) and healthy controls (median 94/mL, range 1-653/mL; p < 0.001). Thirteen IgG4-RD patients (36%) had normal serum IgG4 concentrations (mean 60 mg/dL, range 5-123 mg/dL, normal <135 mg/dL). However, the median plasmablast count was not significantly lower in that subset with normal serum IgG4 concentrations (3784/mL) compared to those with elevated serum IgG4 (5155/mL) (p = 0.242). Among the 12 rituximab (RTX)-treated patients, the median plasmablast level during disease flare was 6356/mL (range 1123-41589/mL), declining to 1419/mL (range 386/mL-4150/mL) during remission (p < 0.01).

CONCLUSIONS:

Circulating plasmablasts are elevated in active IgG4-RD, even in patients with normal serum IgG4 concentrations. Plasmablast counts are a potentially useful biomarker for diagnosis, assessing response to treatment, and determining the appropriate time for re-treatment.

KEYWORDS:

B cells; Disease Activity; Treatment

PMID:
24817416
PMCID:
PMC4656194
DOI:
10.1136/annrheumdis-2014-205233
[Indexed for MEDLINE]
Free PMC Article

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