(448) Pathological autoimmune responses in CF exacerbation

Background: The development of CFTR-directed therapies has widely improved patient well-being in CF. However, despite effectiveness of the new CFTR-directed therapies in improving lung function, their application remains confined to patients harboring specific CFTR mutations. Further, patients still experience acute pulmonary exacerbations (APEs), which are characterized by a systemic inflammatory response that can generate auto-antigens. Here, we investigated the presence of lasting secondary autoimmune responses in patients with CF, which could lead to detrimental and long-lasting effects.

Methods: Blood and sputum were collected from patients with CF at stable state, as well as at the beginning and end of APEs. Immune cells were phenotyped using flow cytometry. Presence of plasma autoantibodies was tested by indirect immunofluorescence in 47 patients with CF and 19 matched healthy controls.

Results: Immune cell phenotyping by flow cytometry showed that plasmablasts, a key cell type in autoimmune diseases, in patients with CF comprised 9.8% of total blood immune cells (3 times higher than mean values of healthy controls), and that CD4⁺ CD28^null T cells (pathogenic T cells present in several autoimmune diseases) were present in the blood at the beginning and end of APEs. Further, anti-epithelial IgG auto-antibodies in CF plasma were increased compared to healthy controls (p = 0.0003) and they inversely correlated with FEV1 (p < 0.009).

Conclusions: Together, these data suggests that patients with CF have presence of autoimmune responses at stable state that are potentiated during APEs, which could further contribute to the decline in lung function.

Acknowledgements: This work was supported by the CFF including RDP Fellowship funded under ROWE19R0 (C.M.), CFF Postdoc-to-Faculty Award MARGAR21F5 (C.M.), and by the NIH HL102371 (A.G.).

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