Higher Levels of Secretory IgA Are Associated with Low Disease Activity Index in Patients with Reactive Arthritis and Undifferentiated Spondyloarthritis

Abstract

Introduction: Both reactive arthritis (ReA) and undifferentiated spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called spondyloarthritis (SpA). Hypotheses have been proposed about a relationship between the intestinal mucosa and inflammation of joint tissues. The role of immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory and/or clinical activity of patients with SpA remains poorly understood.

Objective: To evaluate the status of total IgA and SIgA, and the association among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella spp. with the disease activity measures, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, was compared in a cohort of patients with ReA and uSpA and healthy subjects.

Methods: This was a cross-sectional study. The serum concentrations of SIgA, IgA anti-C. trachomatis, anti-Shigella spp., and total IgA were measured. Disease activity was measured in each patient by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Statistical analysis did include as bivariate evaluation, comparisons by Student's t-test, Kruskal-Wallis test, and U Mann-Whitney test, with a multivariate evaluation by principal components analysis (PCA). A correlation analysis was carried out using the Pearson correlation coefficient and a linear regression models. All analysis were made using Stata version 11.2^® for Windows, R V3.3.21. Statistical significance was defined a p-value <0.05.

Results: In all, 46 patients (78.2% men; mean age, 34.8 ± 12.3 years) and 53 controls (41% men; mean age, 32 ± 11.4 years) were included in the study. The mean serum levels of SIgA were higher in SpA patients than in healthy subjects (p < 0.001). Only SIgA levels correlated with disease activity: BASDAI (r = -0.42, p = 0.0046), ASDAS-CRP (r = -0.37, p = 0.014), and ASDAS-ESR (r = -0.45, p = 0.0021). The negative correlation between SIgA and all activity indices was higher in HLA-B27-positive patients (BASDAI r = -0.70, p = 0.0009, ASDAS-CRP r = -0.58, p = 0.0093, and ASDAS-ESR r = -0.57, p = 0.0083). The PCA showed three factors: the first component was constituted by variables referred as clinical activity measures, the second did include the serological activity markers, and the last component was compounded by age and symptoms time.

Conclusion: Elevated serum levels of SIgA were found to be related with low disease activity in patients with ReA and uSpA.

Keywords: HLA-B27; ankylosing spondylitis; immunoglobulin A; secretory immunoglobulin A; severity of illness index; spondyloarthritis.

Figure 1

Correlation between serum secretory immunoglobulin A (SIgA) and clinical index. A moderate negative correlation was found between SIgA and the disease activity measurements. Correlations were evaluated by Pearson tests. A p value of <0.05 was considered statistically significant. (A) Negative correlation between Bath Ankylosing Spondylitis Disease Activity Index and SIgA (p = 0.0046; r = −0.42). (B) Negative correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and SIgA (p = 0.014; r = −0.37). (C) Negative correlation between ASDAS-erythrocyte sedimentation rate (ESR) and SIgA (p = 0.0021; r = −0.45). x-axis: SIgA in serum (micrograms per milliliter).

Figure 2

Variables vector map—principal component analysis (PCA). This geometric representation of the variables is presented by arrows of a length equal to the standard deviation of the variable. The angle between each pair of arrows represents the correlation between these two variables. Small angles mean a high positive correlation, angles close to 90° no correlation, and angles close to 180° a high negative correlation with opposite directions in the plane. The PCA graph displays the graphical representation of the analyzed components matrix. From the representation, it is extracted that the explanation of the underlying factors that could somehow influence the secretory immunoglobulin A (SIgA) levels together: the first component (PC1) is a factor that represents variables associated with the evaluation of the clinical activity of the disease: Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The second component (PC2) is a factor which group serological variables that are considered soluble markers of activity of the disease and the third component (PC3) aggregates two independent variables as they are age and symptoms that could modify the levels of SIgA. Dim, dimensions.