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Immune-Mediated Clearance Of AL-Amyloid
By Rudi Hrncic, Research Associate, Univ. of Tenn. Medical Ctr.
10.01.00
To investigate potential cellular or humoral elements that can effect amyloidolysis, I developed a novel in vivo experimental model in which 6-week-old Balb/c mice were injected s.c. with up to 200mg (~1% of the mouse’s body weight) of crude human AL (amyloid) extracts.

The resulting "amyloidomas" disappeared within a 2-week period. Histologic studies revealed that no Congo red-positive material (characteristic of amyloid) was present in any of the mouse organs and that the regressing amyloidomas were extensively infiltrated by neutrophils. In contrast, no resolution of the amyloid occurred in old (>1 year) or immunocompromised (e.g. SCID and CD18-deficient) animals. This process was markedly accelerated by the injection at a contra-lateral site of certain anti-human light chain monoclonal antibodies (MoAbs) having specificity for an amyloid-related epitope (as evidenced in vitro by ELISA, flow cytometry, and immunhistochemical analyses).

Remarkably, when mice were treated with such MoAbs, the induced amyloidomas disappeared within 3 to 4 days. From these and other experiments, I have posited that this phenomenon is immune-mediated and involves opsonization of the fibrils by anti-amyloid antibodies and subsequent degradation by activation neutrophils.

These observations form the basis of my proposed project that is designed to:

  • Identify and develop anti-AL MoAbs;
  • Test the capability of these reagents to accelerate resolution of the human amyloidomas in the experimental in vivoanimal model;
  • Investigate immune-related factors that may effect removal of AL deposits.

The ultimate objective of my research is to determine whether this form of immunotherapy would benefit patients with Al amyloidosis.


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