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Proteomic Analysis of Golden Sputum Reveals Pulmonary Complement Activation During Acute Chest Syndrome in Children With Sickle Cell Disease

Year: 2025

Type: article

Abstract: Acute chest syndrome (ACS) is one of the most common severe complications of sickle cell disease (SCD). In recent years, a major role of inflammation and innate immunity has been evidenced, but ACS pathophysiology remains incompletely understood, and therapeutic options are limited. We performed proteomic analysis of induced sputum and tracheal aspirates in eight SCD children during ACS (four intubated and four non-intubated) and in three during vaso-occlusive crisis (VOC) without ACS. Proteomic analysis revealed that one of the main canonical pathways involved during ACS was the complement system. To further investigate its implication, we measured the main components of the complement alternative and terminal pathways in sputum and plasma from SCD children during 27 ACS episodes compared with 16 VOC episodes without ACS. A dramatic increase in the median level of C3a, C5a, sC5b-9, factor B, factor D, properdin, and factor H was observed in the sputum from SCD children during ACS. In the plasma, no significant increase was observed during ACS compared to VOC, except for sC5b-9, whose median level was twofold higher than during VOC but 16-fold lower than the sC5b-9 median level in the sputum during ACS. Also, the C3a/C3 and C5a/C5 ratios were significantly increased in sputum compared to plasma during ACS, reflecting a predominant local pulmonary activation of the complement system compared to systemic activation. Our results reveal the potentially crucial role of complement activation in the lungs during ACS and open new therapeutic perspectives with anti-complement agents for this severe complication of SCD.

Source: American Journal of Hematology

DOI: 10.1002/ajh.70182