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Anti-GM-CSF autoantibodies: A valuable biomarker to predict complicated Crohn’s disease

GM-CSF GM-CSF
GM-CSF GM-CSF

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Antibodies that neutralize immune factor (GM-CSF) implicated in maintaining immune balance in the gut, precede diagnosis by years and anticipate complications in Crohn’s disease.

A study revealed that the serological biomarker anti–GM-CSF autoantibodies (aGMAb) anticipate the diagnosis of Crohn’s disease prior to the disease diagnosis, identifies solely glycosylated epitopes, and impair myeloid cell and innate lymphoid cell balance linked with modified intestinal immune homeostasis. Researchers sought to determine the underlying mechanisms related to aGMAb induction, from the functional orientation to known epitopes, for their influence on intestinal immune homeostasis and utilization as a prognostic biomarker for Crohn’s disease.

Utilizing ELISA, naturally arising aGMab was defined in longitudinal samples of serum from people archived prior to diagnosis of Crohn’s disease (n = 220) along with from 400 healthy people (matched controls) as part of US Defense Medical Surveillance System. For uncovering the mechanism that regulates the weakened immune balance in Crohn’s disease mucosa following diagnosis, transcriptional, cellular, and biochemical assessment was used.

For posttranslational glycosylation on the granulocyte-macrophage colony-stimulating factor (GM-CSF), neutralizing aGMAb was found to be specific, detectable years before diagnosis, and was related to Crohn’s disease at presentation. In patients with Crohn’s disease, alteration of the glycosylation of GM-CSF was observed and aGMAb influenced myeloid homeostasis and was associated with elevated group 1 innate lymphoid cells.

Perturbations in immune homeostasis preceded diagnosis in Crohn’s disease patient's serum presenting with aGMAb, and were identifiable in the mucosa of non-inflamed Crohn’s disease. Hence, this study reported the presence of aGMAb in the sera of Crohn’s disease people years prior to diagnosis, and proposed that these antibodies contribute to Crohn’s disease pathophysiology.

Source:

Gastroenterology

Article:

Neutralizing anti-GM-CSF autoantibodies recognize posttranslational glycosylations on GM-CSF years prior to diagnosis and predict complicated Crohn’s Disease.

Authors:

Arthur Mortha et al.

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