ANCA patients have T cells responsive to complementary PR-3 antigen

Area of Science:

• Immunology
• Autoimmunity

Background:

• Some patients with PR3-ANCA also produce antibodies against cPR3, a protein from the PR3 gene's antisense RNA.
• The presence of cPR3-specific T cells in these patients remains largely uncharacterized.

Purpose of the Study:

• To investigate the existence and characteristics of cPR3-responsive memory T cells in patients with anti-cPR3 antibodies.
• To explore the potential role of these T cells in the pathogenesis of autoimmune diseases.

Main Methods:

• Cultivation of memory T cells under specific conditions, excluding naive cells.
• Assessing T cell responses (proliferation, IFN-gamma secretion) to cPR3 peptides and protein.
• Genotyping for HLA alleles, including HLADRB1(*) 15.

Main Results:

• Approximately half of the patients exhibited CD4+TH1 memory cells responsive to the cPR3(138-169) peptide.
• A third of patients showed T cell responses to HI-PR3 protein.
• T cell responses to cPR3 peptides/protein were significantly higher than in healthy controls and absent in MPO-ANCA patients.
• The HLADRB1(*) 15 allele was overrepresented and predicted to bind cPR3(138-169) peptide.
• A significant correlation was found between anti-cPR3 antibodies and cPR3-specific T cells.

Conclusions:

• The study identified cPR3-specific T cells in patients with PR3-ANCA and anti-cPR3 antibodies.
• These findings suggest an immunological history involving PR3-complementary proteins.
• The presence of T cells reacting to complementary proteins may represent an alternative pathway in autoimmune disease development.