title: Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations.
abstract: OBJECTIVE
  We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD).
  
  
  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.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Wallace
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mattoo
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Mollie
authors.initials: M
authors.lastname: Carruthers
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Vinay S
authors.initials: VS
authors.lastname: Mahajan
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Della Torre
authors.affiliation: Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kulikova
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G
keywords: B cells; Disease Activity; Treatment