P0044 What are the similarities between primary immunodeficiency states and ulcerative colitis: damage to the microbiome, impaired mucosal secretion of proteins and short-chain fatty acids, or something else?
Authors: Iakovlev A A , Bashtovaya O , Volkov A , Tarasova G , Nukhova S , Zubova A , Piskovets V 
Published: January 2025

Abstract

Background
Primary immunodeficiency (PID), common variable immunodeficiency (CVID) are primary immunodeficiencies with disorder of the adaptive immune system, organ-specific pathology, as well as defects in the gut microbiome [1]. In patients with ulcerative colitis (UC) during relapse, similar changes.

Methods
The aim of the research is a comprehensive study of the structure of gut microbiota and mucosal protein profile (MPP) in patients with PID, CVID and UC in different phases of the disease course. The research included 19 patients with PID, 28 with CVID and 32 with UC (22 with relapse and 10 with persistent remission of the disease), control group - 20 healthy volunteers. Estimation of gut microbiota was performed by microbacteriological seeding faeces (MSF). Content of short-chain fatty acids (SCFA) in the feces as determined by gas-chromatography-mass spectrometry (GC-MS). Mucosal protein profile was based on isoelectric focusing techniques (SDS-PAGE, 2DGE). Mass spectrograms were obtained using MALDI-TOF-MS/MS (Bruker, USA). Molecular interaction and functional characteristics of proteins were studied using the STRING 10.0 databases.

Results
SCFA production showed a 6-, 9- and 11-fold decrease in propionic and butyric acids, mainly in patients with PID and UC: 0.2 + 0.1, 0.14 + 0.03 and 0.04 + 0.02, 0.08 + 0.02 mg/g, respectively (tab. 1).
MSF showed a decrease in titers of E. coli, bifido- and lactobacilli on average 4.6 + 0.8 Lg. The conditionally pathogenic microbiota was represented by E. coli, hemolytic strains (n=34,104/g), Proteus spp. (n=48,105/g), Staphylococcus spp. (n=29,105–6/g), Candida alb. / glabrata (n=55,104–6/g) and Clostridium spp. (n = 38,104/g).
Results of MPP (detection rate of 75% or more) of the colon mucosa in patients with PID and CVID were detected: 1, 2, 4 okkludin, kininogen 1, interleukin-1B, interleukin 8, B2-glycoprotein, heat shock protein 27, in patients with CVID - translational elongation factor, apolipoprotein C-III. In patients with UC - NF-kB, alipoprotein C-III, TNF-α, heat shock protein 27, interleukin-2 and 8 were presented. MPP patients with UC (stable remission phase): a-enolase, b-defensin-1, cathepsin D, prohibitin (tab. 2).

Conclusion
1. In patients with PID, CVID and UC during relapse, markers of damage to the intestinal microbiome, a decrease in the production of SCFA and proteins characteristic of inflammation, apoptosis, proliferation, as well as proteins reflecting the activity of the autoimmune process, were identified.
2. During the period of drug remission in patients with UC, PID and CVID, specific components of altered MPP disappear, and a tendency towards restoration of the gut microbiota and SCFA production is recorded.

References
Jørgensen SF, Trøseid M, Kummen M, et al. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol. 2016; 9:1455-1465.