Clinical and diagnostic significance of isolated detection of IgA antibodies to deamidated gliadin peptides in patients with IgA nephropathy

Background. IgA nephropathy (IgA-N) is a serious medical problem as one of the most common causes of terminal renal failure. Modern studies increasingly focus on the role of the intestinal mucosa-associated lymphoid tissue (MALT) in IgA-N pathogenesis, especially in the context of the influence of food antigens, such as gluten. Patients with IgA-N often have antibodies to deamidated gliadin peptides of IgA (DGP IgA AB). The study of their isolated carriage can help in the development of new diagnostic and therapeutic methods aimed at correcting intestinal immunity and controlling the highly active course and progression of IgA-N.

Objective: To establish the clinical and diagnostic role of DGP IgA AB in patients with IgA-N for the development of additional personalized clinical approaches and optimization of treatment strategies.

Material and methods. A total of 105 patients diagnosed with IgA-N aged 18 to 64 years participated in a prospective comparative cohort controlled study. Demographic, anamnestic, clinical, and treatment data were used. The patients' blood serum was tested for antibodies specific for celiac disease: DGP IgA AB; IgA antibodies to tissue transglutaminase (TTG IgA AB); IgA endomysium antibodies. As a result, two groups of patients were formed depending on the presence of DGP IgA AB: the main group (n=20) included IgA-N patients with detected antibodies, and the control group (n=85) consisted of patients seronegative for celiac antibodies. One patient was seropositive for DGP IgA AB and TTG IgA AB simultaneously.

Results. In the patients of the main group IgA-N activity evaluated by the severity of morning proteinuria (0.96 [0.70–1.60] g/l; p=0.005), daily proteinuria (1.50 [0.70–2.50] g/day; p=0.014), erythrocyturia (20.00 [15.00–25.00] in sight; p=0.015), levels of systolic blood pressure (147.65±12.06 mm Hg; p=0.001), and diastolic blood pressure (94.35±12.78 mm Hg; p=0.006) were higher than in the control group. Detection of DGP IgA AB was associated with a high serum IgA concentration (4.35±1.06 g/l; p<0.001). The direct correlation between DPG IgA AB and IgA (ρ=0.247; p=0.020) was most likely due to hyperreactivity of IgA-producing B-lymphocytes of the intestinal mucosa in response to gluten. Patients in the main group had a statistically significantly higher risk of a 50% reduction of the estimated glomerular filtration rate or progression to terminal renal failure within 5 years after performed nephrobiopsy than patients in the control group (15.05% [9.32–20.91] vs. 7.99% [4.97–11.73]; p=0.015).

Conclusion. The obtained results indicate the significance of DGP IgA AB as a potential marker of the risk of IgA-N progression. Further study of the influence of food antigens on the immune response in IgA-N opens up new prospects for the development of effective treatment methods.

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