Ab0014 Histamine and Basophil Granulocytes in Aa Amyloidosis

Background: AA amyloidosis is a severe condition characterized by the deposition of serum amyloid A (SAA) protein in tissues. This protein is produced in excess during an inflammatory response and AA amyloidosis complicates chronic inflammatory diseases [1]. Basophil granulocytes contribute to inflammatory conditions, including diseases that cause AA amyloidosis such as Crohn's disease and mevalonate kinase deficiency [2]. We reported histamine elevation in patients with Familial Mediterranean fever (FMF), another disease that often leads to AA amyloidosis [3]. Patients with both FMF and AA amyloidosis had higher total blood histamine levels than patients with FMF alone. Total blood histamine, as opposed to plasma histamine, which is the amount of histamine secreted by degranulation, reflects intracellular histamine, that is, inside basophils, the only circulating histamine secreting cells. Objectives: The aim of this study was to confirm whole blood histamine elevation and determine basophil activation profile in AA amyloidosis in order to find out if basophils could have a role in AA amyloidosis pathophysiology. Methods: In this monocentric observational study, we prospectively enrolled adult AA amyloidosis patients from the French reference center in Paris (CeRéMAIA). Their clinical characteristics and inflammatory parameters were collected. We measured histamine levels in blood, plasma, and urine, along with serum tryptase. We analyzed basophils' phenotype using flow cytometry, examining activation markers such as CD63, CD107a, CD69 and CD203c and measured a wide range of cytokines by Luminex. We compared patients' histamine, basophil activation markers and cytokine levels to healthy donors. Results: We included thirty AA amyloidosis patients, of whom 19 (63%) were treated. These patients had various underlying inflammatory diseases, including infections (21%), auto-inflammatory diseases (25%), other inflammatory diseases (36%), obesity (28%), and unknown causes (25%). Sixty percent of the patients had CRP levels below 10 mg/L. Total blood histamine levels were higher in the patients compared to healthy controls. The number of basophils was similar in both groups. The expression of CD63 and CD203c was upregulated in AA amyloidosis patients, while the expression of CD107a and CD69 was similar in both groups. Among the measured cytokines, CCL3 and CXCL12 were elevated in patients compared to controls. One patient with a story of severe AA amyloidosis of unknown origin presented particularly elevated blood and plasma histamine levels, along with the highest upregulation of CD203c in the cohort. His whole genome is being sequenced to seek for potential pathogenic variants in basophil or histamine-regulating genes. Conclusion: AA amyloidosis patients exhibit elevated total blood histamine levels and a moderate upregulation of two basophil activation markers, CD63 and CD203c, along with an elevation in two chemokines that can affect basophil recruitment. These results will be complemented with an analysis of basophil infiltration in AA amyloidosis biopsies to understand if basophils could contribute to amyloidosis formation. REFERENCES: [1] Stojanovic et al., 2017; DOI 10.1016/j.nephro.2017.03.001. [2] Karasuyama et al., 2018; DOI 10.1016/j.jaci.2017.10.042. [3] Sbeih et al., 2023; DOI 10.1016/j.ejim.2023.06.009. Acknowledgements: NIL. Disclosure of Interests: None declared.