CD1c Dendritic Cells are depleted and accompanied by new HLA-DR ^hi Phenotypes in Rheumatoid Arthritis Blood

Rheumatoid arthritis (RA) in an autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients ‘share’ a common peptide sequence within the HLA-DR (DR) molecule expressed on antigen-presenting cells (APC), suggesting that DR ^hi cells are important in RA. Here, we use DR ^hi to broadly define and immunophenotype RA APC, including potential APC not meeting standard definitions for lymphocytes, monocytes, dendritic cells (DC) from RA patients and healthy controls (HC). We measured mean fluorescence intensities (MFI) of molecules associated with DC (CD141, CD1c, CD11c, CD123, CD303), monocytes (CD14, CD16); granulocytic markers (CD15, CCR3), co-stimulatory molecules and chemokine receptors. DC2 (CD1c ⁺ ) showed higher CD56, CD86, CD275, and CCR7 in RA. DC2 frequencies were much lower in RA: 3.2% of DR ^hi [IQR 2.41 to 4.46] in RA vs. 6.9% [IQR 3.96 to 9.08] in HC; p=0.005. CD15 was increased in all RA APC subsets (p<0.01). A distinct CD15 ⁺ CD16 ⁺ population appeared in RA, representing 1.5% of leukocytes [IQR 0.68 to 3.32] (vs 0.1% in HC [IQR 0.08 to 0.46]; p<0.001) and contributed a mean of 2.34% to overall DR ^hi . The CD15 ⁺ CD16 ⁺ subset was CD303 ⁺ , CD83 ⁺ and CD275 ⁺ with much less CD123 relative to reference plasmacytoid DC (p<0.01). In conclusion, APC alterations in RA include depletion of DC2 and increased CD15. Moreover, the APC (DR ^hi ) compartment in RA contains cells with shared dendritic cell and granulocytic features; this phenotype suggests these apparent APC may participate in the pathophysiology of rheumatoid arthritis via the presentation of self-antigen(s) to CD4 ⁺ T lymphocytes.