Th186 - Mechanistic Differences Between Childhood and Adult-onset Systemic Lupus Erythematosus

Abstract Text: Patients with childhood-onset SLE (cSLE) have more severe manifestations and accrue more end-organ damage compared to their adult counterparts. Despite these, cSLE treatment is often extrapolated from adult studies with the assumption that they are similar. Its immunopathogenic complexity and a lack of insight into the mechanistic differences between childhood and adult-onset lupus demand their holistic comparison.

We interrogated the peripheral blood mononuclear cells from 26 adult-onset and 26 childhood-onset SLE patients with mass cytometry. Batch-effect correction, cell clustering and visualisation were done. Frequencies were expressed as percentages of PBMC with median and Inter-quartile ranges. Statistical significance was defined as p< 0.05 (Mann-Whitney U test).

There were cSLE-specific changes with an increase in memory (CD45RA-) HLADR+OX40+CLA+CD4+ (SLE versus healthy: 0.26 [0.14 to 0.39]% versus 0.10 [0.05 to 0.17]%, p< 0.0001), memory IL2+IL21+CD4+ (0.41 [0.23 to 0.68]% versus 0.17 [0.13 to 0.29]%, p=0.0002) and memory CD25-FoxP3+CTLA4+TIGIT+CLA+CD4+ T cells (0.68 [0.36 to 1.24]% versus 0.35 [0.25 to 0.53]%, p=0.0038).

Conversely, the naïve and memory effector CD4+ T cells (CD25-FoxP3-) expressing CTLA4 were reduced in adult lupus (1.61 [0.85 to 2.62]% versus 4.65 [3.20 to 7.18]%, p< 0.0001 and 0.54 [0.34 to 0.79]% versus 1.46 [1.00 to 2.06]%, p< 0.0001 respectively).

The increase of cSLE-specific memory CD4+ T cells expressing OX40, IL21 and skin-homing (CLA+) T regulatory-like (CD25-Foxp3+) cells expressing immune checkpoint inhibitors (CTLA4 and TIGIT) suggest a distinct immunopathogenic mechanism from adult-onset SLE. The reduced CTLA4 expression in CD25-FoxP3- T cells suggests a perturbed negative feedback mechanism in adult lupus.