Abstract

Introduction: autoimmune hemolytic anemia (AIHA) is a rare clinical condition with hemolysis mediated by immunoglobulin binding on the surface of erythrocytes with or without complement activation. Metaboloma is the sum of the genetic configuration of an organism to the external factors. The metabolic profile involved in AIHA has not yet been described and may be the key to new findings about the mechanism of autoimmune hemolysis.

Objectives: To describe a profile of AIHA related metabolites, increased hemolysis and risk of relapse.

Patients andMethod: we analyzed the plasma from 31 patients with primary AIHA compared to plasma from 150 healthy subjects using mass spectrometry (Kit AbsoluteIDQ p180, Biocrates, Austria). The statistical analysis was performed by the software available at http://www.metaboanalyst.ca/.

Results: of the 95 metabolites found in patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were increased with great statistical significance. There was an increase in PCs and polyamines (spermine and spermidine) in the AIHA group in hemolytic activity. The relationship between PCs "PC ae 34: 3 / PC ae 40: 2" seen only in the 12-months relapsed group was predictor of relapse with specificity of 81% and sensitivity of 100%.

Discussion: Increased sphingomyelin in AIHA patients may perpetuate deficient regulatory T lymphocytes in the recognition of erythrocytes as self. Accumulation of ADMA can cause downregulation of NF-kβ from macrophages by inducing one of the already known autoimmune mechanisms. Excess PCs in patients with AIHA and increased hemolysis may perpetuate effector T lymphocytes with increased susceptibility to autoimmunity and increase the production of antibodies against erythrocyte antigens. The increase of polyamines in the higher hemolysis group may induce autoimmunogenicity of DNA and interfere with the differentiation of macrophages. Finally, the presence of PC to 34: 3 / PC to 40: 2 as a predictor of relapse may help to identify cases that require follow-up more frequently or second-line therapies earlier.

Conclusion: Our data demonstrate a distinct profile of metabolites in AIHA patients, as well as in individuals with higher hemolytic activity. There was a relationship of phosphatidylcholines strongly predictive of AIHA relapse.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.