In spondyloarthritis (SpA) patients, an increased gut permeability and an asymptomatic intestinal inflammation, usually affecting the ileum and independent from the use of nonsteroidal anti-inflammatory drugs, have been reported in several studies.1,2

Anti-Saccharomyces cerevisiae antibodies (ASCA), which are rarely positive in healthy controls (<5%), possess clinical significance in inflammatory bowel disease (IBD) management.2–4 This serological biomarker is more commonly elevated in Crohn's disease (CD) than in ulcerative colitis (UC), presenting a sensitivity of approximately 72% and a specificity of 82% in CD.2–6

Because SpA and IBD share similarities and following the hypothesis that increased gut inflammation and consequent loss of mucosal immune tolerance is of etiopathogenic importance in the development of SpA, evaluation of these antibodies has gained increasing relevance.4,7

An increased prevalence of these serologic markers of IBD in SpA patients could sustain an additional pathophysiological link between the two entities.1 Furthermore, identification of new biomarkers can represent an advance for the early diagnosis of SpA as well as of important associated clinical manifestations and, consequently, this can be reflected in a significant improvement of therapeutic management.2

Although some studies have shown ASCA seropositivity to be more common among SpA patients than in healthy controls, the relationship of the antibodies status and the disease phenotype remain unclear and poorly described in literature.1,6,8 In the present study, we purpose to investigate the status and frequency of ASCA in SpA patients and the association of these serological markers with the clinical profile.

We included a group of 231 patients with SpA, 117 of which were men (51%), with a mean age of 48.6±12.5 years. The median disease duration was 17 years [min: 2; max: 53].

In total, 39% of the patients had axial SpA (n=90), 10% peripheral SpA (n=23) and 51% presented axial and peripheral SpA (n=118). Nine patients had associated IBD (7 cases with CD and 2 with UC) and 66 patients exhibited concurrent psoriasis (28.6%). Ninety-four patients (68.6%) were HLA-B27+ and 59 (26%) presented history of uveitis (current or previous). Less than half of the patients had active or past smoking habits (n=102; 44%). The clinic and demographic characteristics are summarized in Table 1.

ASCA IgA were positive in 14% of the whole sample (n=33; 14 patients with axial involvement, 4 with peripheral involvement and 15 with axial and peripheral involvement). ASCA IgG positivity was found in 5% of the SpA (n=12; 7 patients with axial involvement, 1 with peripheral involvement and 4 with both involvements). The median ASCA IgA and IgG titres were 72RU/mL [min: 22; max: 200] and 45.5RU/mL [min: 28; max: 200], respectively.

As expected, ASCA IgA positivity was associated with presence of IBD (12.1% vs 2.5%; p=0.026). We verified the same relationship with ASCA IgG positivity (25% vs 2.7%; p=0.008). Despite these results, we found no statistically significant differences in the number of ASCA IgA or IgG-positive patients according to the type of IBD-CD vs UC (p=0.722 and p=0.583, respectively).

Current age and at time of diagnosis, disease duration, gender, tobacco use were similar between ASCA IgA or IgG-positive and negative groups. Also, disease phenotype including type of involvement, presence of psoriasis or uveitis and HLA-B27 positivity were unrelated to ASCA IgA and IgG status (Table 2).

Our results showed that SpA patients present an increase of ASCA IgA positivity, in agreement to previous data. Of interest, we also noticed that this evidence is mainly directed to the IgA subclass and no to IgG antibodies, as observed in others reports.1,2,4,5,7

Although the raise of ASCA in SpA patients, the data regarding the role of ASCA in the clinical profile and prognostic disease of Spa patients remain discordant.

In 2016, Maillet et al. found that the presence of ASCA was associated with a particular SpA phenotype characterized by the absence of axial involvement, presence of IBD, arthritis and past or present history of uveitis.11

In contrast, Hoffman et al. did not find differences in ASCA IgA levels comparing patients with or without peripheral synovitis.4 Also, in the study of Marianne et al. no association of ASCA IgA could be demonstrated with the occurrence of peripheral arthritis or uveitis or with the presence of HLA-B27.7

In our study, we did not find any relationship of ASCA status and the demographic aspects, genetic factors or clinical presentation, except the association with presence of IBD. However, despite the differences were not statistically significant, a higher number of patients with ASCA IgA and IgG positivity was found in whom axial involvement was present.

The data published in 2014 by Praet et al. support that gut inflammation is linked to progressive disease in axial SpA through the evidence of higher degrees of bone marrow oedema in sacroiliac joints, assessed by the Spondyloarthritis Research Consortium of Canada scoring system, in SpA patients with histological findings of chronic mucosal lesions.12

Also, according to Aydin et al., patients with positivity to ASCA had greater severity of spine radiological damage evaluated by the Bath Ankylosing Spondylitis Radiology Index, suggesting its potential role as a marker of structural disease progression.5

Some theories point that an increased intestinal permeability in SpA, as shown by ASCA positivity, can be related to a higher radiological damage as a result of ongoing antigenic stimulus.5 The present study was not designed to evaluate the impact of ASCA status in the structural and radiological damage, but further prospective studies are warranted to clarify the previously speculated hypothesis.

A limitation of the current study is that all the SpA patients included were under biologic therapy, which might raise issues about a possible influence on antibody reactivity. Nevertheless, it has been demonstrated that antibody responses do not change over time or as a result of drug therapy, including biologic therapy.13

In the future, more studies would be necessary to investigate the relationship between antibody reactivity and endoscopic findings in SpA patients. Additionally, it would be interesting to assess the faecal calprotectin levels, since it is a recognized standard clinical biomarker of IBD activity and recently, as suggested by Moreno Martínez et al. a parameter elevated in SpA patients which correlates positively with C-reactive protein.8,14 Finally, a longer follow-up of these patients, assessing the onset of new gastrointestinal symptoms and the subsequent development of IBD, will be critical in determining if the presence of ASCA is a predictive marker of the SpA phenotype.

None declared.