In patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), total globulin fraction (TGF) at diagnosis may serve as a predictor of all-cause mortality, according to findings from a single-center, retrospective study.

AAV, which is associated with necrotizing vasculitis, can be classified into 3 subtypes, according to the presence of granulomatosis formation and eosinophilic infiltration:

  • Microscopic polyangiitis (MPA)
  • Granulomatosis with polyangiitis (GPA)
  • Eosinophilic granulomatosis with polyangiitis (EGPA).

Individuals with AAV have rates of all-cause mortality that are reported to be higher than those among patients with other vasculitides. The researchers sought to explore whether TGF calculated at diagnosis of AAV can predict all-cause mortality throughout the disease course among patients with MPA, GPA, and EGPA.

TGF (g/dL), which is measured by subtracting serum albumin levels (g/dL) from serum total protein levels (g/dL), includes alpha-globulins, beta-globulins, and gamma-globulins.

Because most alpha-globulins are acute-phase reactants, whereas gamma-globulins are immunoglobulins, it is thought that TGF will be reflective of the extent of various immune reactions, along with the degree of inflammatory burden that exists.

A total of 283 participants with AAV (155 with MPA, 72 with GPA, and 56 with EGPA) enrolled in the Severance Hospital ANCA-associated VasculitidEs (SHAVE) cohort were included in the current study. SHAVE is an observational cohort that comprises individuals initially diagnosed with AAV at the Yonsei University College of Medicine, Severance Hospital, in Seoul, Republic of Korea, between October 2000 and July 2020.

Learn more about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis

The following patient variables were obtained at AAV diagnosis:

  • Demographic characteristics (age, sex, body mass index [BMI], smoking status)
  • AAV subtype
  • ANCA type and positivity
  • Myeloperoxidase (MPO)-ANCA
  • Proteinase 3 (PR3)-ANCA
  • Perinuclear (P)-ANCA
  • Cytoplasmic (C)-ANCA
  • Laboratory data (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] level)
  • AAV-specific indices
  • Birmingham Vasculitis Activity Score (BVAS)
  • Five-Factor Score (FFS).

The median participant age was 60 years. Overall, 35.7% of the patients were men. Results of the study showed that MPO-ANCA (or P-ANCA) and PR3-ANCA (or C-ANCA) were detected in 195 and 45 participants, respectively. Median values reported were as follows:

  • BVAS: 12.0
  • FFS: 1.0
  • ESR: 56.0 mm/h
  • CRP level: 13.2 mg/L

At AAV diagnosis, the median TGF was 2.9 (range, 2.6 to 3.4). ANCAs were detected in 228 of the participants. A total of 39 patients died within a median follow-up of 46.9 months.

Although TGF at diagnosis of AAV was not associated with BVAS or FFS at diagnosis, it was statistically significantly associated with ESR and CRP level assessed at diagnosis (P <.001 for both). TGF at AAV diagnosis in participants with MPA or MPO-ANCA (or P-ANCA) positivity was slightly increased compared with TGF in those with GPA and EGPA or those with MPO-ANCA (or P-ANCA) negativity, but the difference was not significant.

TGF at diagnosis of AAV  was statistically significantly associated with CRP and ESR, but not with AAV activity. Participants with ANCA positivity demonstrated a significantly higher median TGF at diagnosis of AAV compared with those without ANCA positivity. Individuals with TGF of 3.1 g/dL or higher had a significantly lower cumulative survival rate compared with those without. Additionally, per multivariable Cox hazards model analysis, TGF of ≥3.1 g/dL was independently linked to all-cause mortality, age, male sex, and BMI.

“The present study is the first to demonstrate that TGF at AAV diagnosis can forecast all-cause mortality during the disease course in [patients with AAV],” the researchers concluded.


Ha J-W, Ahn S-S, Song J-J, Park Y-B, Lee S-W. Total globulin fraction at diagnosis could forecast all-cause mortality during the disease course in patients with antineutrophil cytoplasmic antibody-associated vasculitis. J Clin Med. 2023;12(12):4170. doi:10.3390/jcm12124170