Lower serum interleukin-22 and interleukin-35 levels are associated with disease status in neuromyelitis optica spectrum disorders

Abstract

Aims: The exact pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) remains unclear. A variety of cytokines are involved, but few studies have been performed to explore the novel roles of interleukin-22 (IL-22) and interleukin-35 (IL-35) in NMOSD. Therefore, this study was designed to investigate serum levels of IL-22 and IL-35, and their correlations with clinical and laboratory characteristics in NMOSD.

Methods: We performed a cross-section study, 18 patients with acute NMOSD, 23 patients with remission NMOSD, and 36 healthy controls were consecutively enrolled. Serum levels of IL-22 and IL-35 were measured by enzyme-linked immunosorbent assay (ELISA). The correlations between serum IL-22 and IL-35 levels and clinical and laboratory characteristics were evaluated by Spearman's rank or Pearson's correlation coefficient.

Results: The serum levels of IL-22 and IL-35 were significantly lower in patients with acute NMOSD and remission NMOSD than in healthy controls (IL-22: 76.96 ± 13.62 pg/mL, 87.30 ± 12.79 pg/mL, and 94.02 ± 8.52 pg/mL, respectively, P < .0001; IL-35: 45.52 ± 7.04 pg/mL, 57.07 ± 7.68 pg/mL, and 60.05 ± 20.181 pg/mL, respectively, P < .0001). Serum levels of IL-35 were negatively correlated with EDSS scores and cerebrospinal fluid protein levels (r = -.5438, P = .0002 and r = -.3523, P = .0258, respectively) in all patients.

Conclusions: Lower serum levels of IL-22 and IL-35 are associated with disease status in NMOSD. Additionally, lower serum levels of IL-35 are associated with disease severity in NMOSD.

Keywords: immunosuppression; interleukin-22; interleukin-35; neuromyelitis optica spectrum disorders.

Figure 1

A, Serum interleukin‐22 (IL‐22) levels in patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls. Using one‐way ANOVA, we found there were significant differences among the three groups (P < .0001). Using LSD multiple comparisons test for acute NNOSD and HC, acute NMOSD and remission NMOSD, and remission NMOSD and HC, we found there were significant differences (P ¹ < .0001, P ² < .01, and P ³ < .05, respectively). B, Serum interleukin‐35 (IL‐35) levels in patients with NMOSD and healthy controls. Using one‐way ANOVA, we show there were significant differences among the three groups (P < .0001). Using LSD multiple comparisons test for acute NMOSD and HC, acute NMOSD and remission NMOSD, and remission NMOSD and HC, we show there were significant differences (P ¹ < .0001, P ² < .01, and P ³ < .01, respectively; *P < .05; **P < .01; ***P < .001; ****P < .0001)

Figure 2

A, B, C, Using the Pearson correlation coefficient, we shown there were no correlations between serum interleukin‐35 (IL‐35) levels and serum interleukin‐22 (IL‐22) levels in the total neuromyelitis optica spectrum disorder (NMOSD), acute NMOSD and remission NMOSD groups (r = .2748, P = .0821; r = .4529, P = .0591; and r = −.2346, P = .2813, respectively)

Figure 3

A, Using Spearman's rank correlation coefficient, we show that there was a negative correlation between serum interleukin‐35 (IL‐35) levels and cerebrospinal fluid (CSF) protein levels in the total neuromyelitis optica spectrum disorder (NMOSD) group (r = −.3523, P = .0258). B, Using the Pearson correlation coefficient, we show there was no correlation between serum IL‐35 levels and CSF protein levels in the total NMOSD group (r = .2838, P = .2538). C, Using Spearman's rank correlation coefficient, we show there was no correlation between serum IL‐35 levels and CSF protein levels in the remission NMOSD group (r = −.2447; P = .2724). D, E, F, Using Spearman's rank correlation coefficient, we show there were negative correlations between serum IL‐35 levels and EDSS scores in the total NMOSD and acute NMOSD groups (r = −.5438, P = .0002; and r = −.6696, P = .0024; respectively), but there was no correlation in the remission NMOSD group

Figure 4

A, B, C, Using Spearman's rank correlation coefficient or Pearson's correlation coefficient, we show there were no correlations between serum interleukin‐22 (IL‐22) levels and cerebrospinal fluid (CSF) protein levels in the total neuromyelitis optica spectrum disorder (NMOSD), acute NMOSD, and remission NMOSD groups (r = −.1573, P = .3324; r = −.03406, P = .8933; and r = .0278, P = .9023, respectively). D, E, F, Using Spearman's rank correlation coefficient, we show there were no correlations between serum IL‐22 levels and EDSS scores in the total NMOSD, acute NMOSD, and remission NMOSD groups (r = −.2289, P = .1499; r = −.3033, P = .2212; and r = .02916, P = .8949, respectively)