Serum IgA levels and survival in patients with idiopathic pulmonary fibrosis: association with serum cytokine levels and peripheral monocyte counts

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is an idiopathic fibrotic interstitial lung disease with poor prognosis. Recently, the prognostic value of serum platelet-derived growth factor (PDGF) levels in patients with IPF has been clarified. Monocyte counts in the peripheral blood have also been reported to be an important predictor of survival in IPF. This study aimed to clarify the prognostic value of serum immunoglobulin (Ig) A levels in patients with IPF to predict survival and occurrence of acute exacerbations (AE).

Methods: This retrospective study included 71 patients diagnosed with IPF based on the 2022 guidelines. Serum PDGF and interleukin (IL)-10 levels were measured using the Bio-Plex method. IgA levels were measured by a clinical testing company.

Results: Of the enrolled patients, 59 were male, and the median age of the sample was 67 [interquartile range (IQR): 61-72] years. The median serum IgA level was 307 (IQR: 232-408) mg/dL and 18 patients had serum IgA levels of >400 mg/dL. Univariate Cox proportional hazard regression analysis revealed that high IgA levels (>400 mg/dL) were a significant predictor of poor prognosis; however, monocyte counts were not. A high IgA level was a significant prognostic factor after adjusting for the percent predicted value of forced vital capacity, age, gender, and body mass index. Serum PDGF levels tended to be higher in patients with high IgA levels than in those with low IgA levels. IL-10 was not significantly correlated with IgA levels; however, IgA levels tended to be negatively correlated with monocyte counts. High IgA levels did not significantly predict AE. High monocyte counts (>600/µL) significantly predicted the early incidence of AE by univariate Cox analysis but was not confirmed by multivariate analysis. However, monocyte counts, and a monocyte count of >600/µL were significant predictors of AE occurrence for patients with low IgA ≤400 mg/dL.

Conclusions: The serum IgA level is an independent prognostic predictor of survival in patients with IPF. Serum IgA levels might suggest serum fibrogenic cytokine levels. Serum IgA levels might be associated with prognosis differently from peripheral monocyte counts. The pathophysiological role of IgA needs to be elucidated in future studies.

Keywords: Idiopathic pulmonary fibrosis (IPF); acute exacerbation (AE); interleukin-10 (IL-10); platelet-derived growth factor (PDGF); prognosis.

Figure 1

Survival curves of patients with IPF. (A) Patients with high IgA levels (>400 mg/dL, n=18, solid line) have significantly worse survival than those with low IgA levels (≤400 mg/dL, n=53, dotted line) (Log-rank test, P=0.007). (B) No significant difference in survival rates is observed between patients having IPF with high monocyte counts (>600/μL, n=8, solid line) and those with low monocyte counts (≤600/μL, n=63, dotted line) (Log-rank test, P=0.38). IgA, immunoglobulin A; IPF, idiopathic pulmonary fibrosis.

Figure 2

Incidence of AE in patients with IPF. (A) Patients with high IgA levels (>400 mg/dL, n=18, solid line) tend to have a higher incidence of AE than those with low IgA levels (≤400 mg/dL, n=53, dotted line) (Log-rank test, P=0.08). (B) The incidence of AE in patients with IPF with high monocyte counts (>600/μL, n=8, solid line) is significantly higher than that of patients with low monocyte counts (≤600/μL, n=63, dotted line) (Log-rank test, P=0.02). AE, acute exacerbation; IgA, immunoglobulin A; IPF, idiopathic pulmonary fibrosis.