Association of blood lymphocyte subsets with disease progression in connective tissue disease associated interstitial lung disease (CTD-ILD): a subanalysis of the RECITAL cohort

Introduction. Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a collection of systemic autoimmune disorders resulting in lung interstitial abnormalities or lung fibrosis. Lymphocyte subsets likely play a crucial role in the pathogenesis of CTD-ILD, but many implications remain to be clarified. Aim: to assess the association of blood lymphocyte subsets with CTD-ILD and disease progression in the RECITAL population. Materials and methods: one hundred and one patients with severe or progressive ILD related to scleroderma (SSc), idiopathic inflammatory myositis (IIM), or mixed CTD (MCTD) were recruited as part of the RECITAL study. Eighty seven out of 101 patients were considered. Blood lymphocyte subsets (CD3+, CD4+, CD8+, NK, B) and lung function tests at baseline, 24 and 48 weeks were used. Progression of the disease was assessed as forced vital capacity (FVC) decline > 10% a/o diffusing capacity of the lungs for carbon monoxide (DLCO) decline > 15% or FVC decline > 5% a/o DLCO decline > 5% over one-year of follow-up. According to latest literature research, a cut off of 5 cell/uL as definition of B cells depletion was established (doi.org/10.1016/j.clim.2023.109265). Results: According to our data, no association has been assessed between lymphocyte subsets and disease progression (both defined as FVC decline > 10% a/o DLCO decline > 15% and FVC decline > 5% a/o DLCO decline> 5%). Baseline lymphocyte B (%) is higher in IIM-ILD than SSC-ILD (20 % (6-44) vs 15 (2-32); p 0.04) and, at corrected univariate analysis, they are predictor of IIM-ILD diagnosis [OR 1.08, 95%CI (1.01-1.16); p 0.023]. Lymphocyte CD8+, both as concentration and percentage, are protective against the occurrence of IIM-ILD diagnosis [OR 0.99, 95%CI (0.99-0.99); p 0.006] and [OR 0.91, 95%CI (0.85-0.97); p 0.009], respectively. In the rituximab-treated population, B cells depleted group at 48 weeks has lower B cell concentration at the baseline compared to non-depleted group [288 c/uL (31- 1111) vs 449 (80- 1623); p= 0.39]. Patients who display depleted B cell at 48 weeks have an increased Δ FVC at one year follow up compared to non-depleted group [260 mL(-210- 660) vs 35 (-350- 490); p= 0.019 ]. B cell concentration at 48 weeks inversely correlates with delta FVC (mL) at one year follow up (r=-0.46, p=0.02). Conclusions: Lymphocyte subsets are not associated with CTD-ILD progression. Their role as disease markers is uncertain even if lymphocyte B as percentage may play a role as predictor of IIM-ILD diagnosis, while CD8+, both as concentration and percentage, seems protective against this diagnosis. In patients treated with rituximab, at one year follow-up, having B cell concentration lower than 5 cell/uL is associated with an FVC improvement and may guide the clinician in the decision of redosing rituximab.