Understanding the Gut-Joint Connection in Spondyloarthritis and Celiac Disease

Celiac.com 07/18/2025 - Spondyloarthritis (SpA) is a group of inflammatory diseases that primarily affect the spine and joints but also have surprising connections to gut health. Many patients with spondyloarthritis experience intestinal inflammation, even if they don’t have inflammatory bowel disease (IBD). Researchers have long suspected that immune responses in the gut might influence joint inflammation, but the exact mechanisms remain unclear.

A key player in this process is secretory immunoglobulin A (SIgA), an antibody that helps protect the gut lining. High levels of SIgA in the blood have been found in spondyloarthritis patients, suggesting an overactive gut immune response. This study investigated how two proteins, CD71 and Dectin-1 (Dec-1), might contribute to this process by transporting SIgA from the gut into the bloodstream—a mechanism called retrotranscytosis.

Study Design and Key Findings

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Who Was Studied?

The research involved 41 spondyloarthritis patients with signs of gut inflammation but no diagnosed IBD. Most were male (56%), with an average age of 45. The majority had axial (spinal) or peripheral joint involvement, along with symptoms like inflammatory back pain, enthesitis (inflammation where tendons attach to bones), and arthritis.

What Did Researchers Measure?

• Gut inflammation: Using colonoscopy and biopsies.
• Blood markers: Including SIgA, C-reactive protein (CRP), and calprotectin (a stool marker of gut inflammation).
• Disease activity: Using standard spondyloarthritis scoring systems (BASDAI, ASDAS).
• Protein expression: Checking for CD71 and Dec-1 in gut tissue.

Major Discoveries

1. CD71 and Dec-1 Were Found in the Gut

• Both proteins were detected in the ileum (small intestine), particularly in areas with inflammation.
• CD71 was linked to higher blood SIgA levels, suggesting it helps transport SIgA into circulation.
• Dec-1 was associated with visible gut damage, like villi atrophy (flattening of intestinal folds).

2. Higher SIgA Correlated with Worse Disease Activity

• Patients with more CD71 in their gut had higher spondyloarthritis disease activity scores.
• This supports the idea that gut inflammation fuels joint inflammation.

3. No Direct Interaction Between CD71 and Dec-1

• While both proteins were present, they didn’t physically bind to each other.
• However, their combined presence was linked to more severe gut damage.

What This Study Means for People with Celiac Disease

Key Findings: Gut Inflammation and Immune Triggers

This study on spondyloarthritis reveals crucial insights about how gut inflammation can trigger systemic immune reactions—findings that may directly impact those with celiac disease. Researchers discovered that:

• CD71, a protein linked to celiac disease, was found in the gut lining of spondyloarthritis patients.
• High SIgA (secretory immunoglobulin A) levels in the blood correlated with gut damage and inflammation.
• Retrotranscytosis (a process where immune molecules like SIgA leak from the gut into the bloodstream) may worsen autoimmune reactions.

Why This Matters for Celiac Disease

1. Shared Mechanism with Celiac Disease

• CD71 is already known to play a role in celiac disease by helping transport gluten-antibody complexes into the bloodstream.
• This study suggests that similar pathways may drive inflammation in other autoimmune conditions, including spondyloarthritis.

2. Gut-Joint Connection

• Many celiac patients also suffer from joint pain and arthritis-like symptoms.
• This research supports the idea that leaky gut and SIgA transport could explain why some celiac patients develop joint inflammation.

3. Potential for Better Diagnosis

• If high SIgA levels signal gut damage in spondyloarthritis, the same may apply to celiac disease.
• Blood tests for SIgA could help monitor hidden gut inflammation in celiac patients, even if they follow a gluten-free diet.

Implications for Celiac Disease Management

1. Stronger Focus on Gut Healing

Since CD71 and SIgA are linked to gut permeability, celiac patients may benefit from:

• Strict gluten avoidance to reduce immune triggers.
• Probiotics and gut-healing diets (e.g., low-FODMAP, anti-inflammatory foods) to strengthen the intestinal barrier.

2. Monitoring for Related Autoimmune Conditions

• Celiac patients with unexplained joint pain should consider screening for spondyloarthritis or other autoimmune disorders.
• Doctors may need to check for gut inflammation even in celiac patients who are "strictly gluten-free" but still have symptoms.

3. Future Treatments Targeting Retrotranscytosis

• If blocking CD71 or SIgA transport helps spondyloarthritis patients, similar therapies could be explored for refractory celiac disease.
• Research into leaky gut treatments (like zonulin inhibitors) may become more relevant.

Conclusion: A New Perspective on Celiac-Related Inflammation

This study highlights that celiac disease isn’t just about gluten—it’s about how gut inflammation fuels systemic autoimmunity. Key takeaways:

• CD71 and SIgA may worsen inflammation in both celiac disease and spondyloarthritis.
• Joint pain in celiac patients could stem from gut-driven immune reactions.
• Better diagnostic tools and treatments targeting gut permeability could emerge from this research.

For celiac patients, this means:

• More reason to prioritize gut health beyond just avoiding gluten.
• Potential for new therapies that address leaky gut and abnormal immune transport.
• Greater awareness of how celiac disease may overlap with other autoimmune conditions.

While more research is needed, this study reinforces the importance of treating celiac disease as a systemic disorder—not just a digestive one.

Read more at: nature.com