#2240 The complex fluctuation of circulating T follicular cells in patients with lupus nephritis (LN)

Abstract Background and Aims Follicular T (TF) cells constitute a subgroup of cells recently discovered, located in the germinal center (GC) of lymphoid follicles, where they mediate B lymphocyte development, maturation, and antibody production. Meanwhile, T cells with similar markers have also been detected in the peripheral blood, considered as a circulating memory compartment with unknown origin or function. TF cells seem to be implicated in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN) by assisting the selection of high-affinity B cells in germinal centers; nonetheless, research about their circulating regimen is lacking. Herein, we describe the population of circulating TF cells in patients with LN and their association with disease hallmarks. Method Flow cytometry was performed to identify cTF (CD4+CD45RA-CXCR5+) cells and their subsets, defined as cTF1 (CD4+CD45RA-CXCR5+CXCR3+CCR6-), cTF2 (CD4+CD45RA-CXCR5+CXCR3-CCR6-), cTF17 (CD4+CD45RA-CXCR5+CXCR3-CCR6+), and activated-cTF, cTF-ICOS+ (CD4+CD45RA-CXCR5+ICOS+), as well as cTF-Regulatory (cTFR) (CD4+CD45RA-CXCR5+CD127-CD25+FOXP3+). Peripheral blood was collected from 25 LN patients (LN) and 25 healthy controls (HC) of similar age. Results Here are presented preliminary results analyzed in 15 LN patients (age = 38 ± 8yrs) and compared to 9 HC (age = 31.5 ± 7yrs). Although our findings were not significant in total and the percentage and total number of cTFH cells were similar between LN and HC [7.1 (0.6-22.4)% and 52.57 (3.38-412.7)cells/μL, vs. 6.6 (1.9-12.1)% and 45.65 (13.3-69.6)cells/μL, respectively], the fluctuation of the different subsets is interesting. cTF-ICOS+, cTF1, cTF2, and also surprisingly cTFR cells were upregulated in LN compared to HC [0.9 (0-5.2) vs 0.51 (0-1.45)cells/μL, 9.3 (0.2-31.6) vs. 3.02 (0.4-23.08)cells/μL, 10.89 (0-47.41) vs 3.37 (0.46-39.01)cells/μL, and 0.21 (0-12) vs 0.12 (0-1.53) cells/μL, respectively], while the cTF17 compartment was condensed [5.36 (0.79-213.8) vs 8.37 (0.22-29.2)cells/μL, respectively]. Clinical and laboratory markers of the disease were then assessed, resulting in a strong positive correlation of the SLEDAI score with the percentage of cTF2 and cTFR (r = 0.643 and 0.706, respectively) and of C3 levels with cTF percentage (r = 0.663) and cTF-ICOS (+) number (r = 0.719) while the correlation was negative between C4 levels with the percentage of cTF1 (r = −0.577) and cTF2 (r = −582) and between ANA antibody levels and cTF-ICOS (+) cells (r = −657). The analysis did not show any association between the anti-dsDNA antibody levels and the understudied subpopulations. Conclusion cTF cells tend towards 1 and 2 rather than the 17 phenotype in LN. From the various subsets, cTF2 appear to serve as a possible monitoring marker. Certainly, the complexity of the disease imposes further investigation.