Adaptive immune system in pulmonary sarcoidosis - comparison of peripheral and alveolar biomarkers

Sarcoidosis is a multisystemic granulomatous disease of unknown origin. Recent research has focused on the role of autoimmunity in its development and progression. This study aimed to determine and define disturbance and distribution of T- and B-cell subsets in the alveolar and peripheral compartments. Thirteen patients were selected for the study (median age (IQR), 57 years (48-59); 23% were males). Twelve healthy controls (median age (IQR) 53 years (52-65); 16% males) were also enrolled in the study. Cellular and cytokine patterns were measured through cytofluorimetric approach. Peripheral CD8% were higher in sarcoidosis patients (SP) than healthy controls (HC) (p=0.0293), while CD4% were lower (p=0.0305). SP showed low BAL percentages of CD19 (p=0.0004) and CD8 (p=0.0035), while CD19+ CD5+ CD27- % were higher (p=0.0213); the same was found for CD4 (p=0.0396), follicular Treg (p=0.0078) and Treg (p<0.0001) cells. Low Th17% were observed in BAL (p=0.0063) of SP. Peripheral CD4+ CXCR5+ CD45RA- % and Tfh-like Th1 (Tfh1)% (p=0.0493 and p=0.0305, respectively) were higher in the SP than HC. Tfh1% and Tfh-like Th2 % were lower in BAL than in peripheral blood (p=0.0370 and p=0.0078, respectively), while CD4+ CXCR5+ CD45RA- % were higher (p=0.0011). This is the first study to demonstrate a link between imbalance in circulating and alveolar Tfh cells, especially CCR4-, CXCR3- and CXCR5-expressing Tfh subsets, in the development of sarcoidosis. These findings raise questions about the pathogenesis of sarcoidosis and may provide new directions for future clinical studies and treatment strategies.