Synthetic peptides for the diagnosis and therapy of beryllium granulomatous disease

Kurzfassung

An Italian university research group has identified peptides that present the capability to block or to increase the response to beryllium of the beryllium-specific T-lymphocytes in subjects with Chronic Beryllium Disease. The researchers are looking for a pharmaceutical company for commercial agreement with technical assistance or technical cooperation.

Details

This patent is relative to the identification of peptides that present the capability to block or to increase the response to beryllium of the beryllium-specific T-lymphocytes in subjects with Chronic Beryllium Disease.
These peptides have been designed taking in considerations:
- the capability of binds with high affinity the molecules of the Major Histo-compatibility Complex (Human Leucocyte Antigen, HLA) belonging to the variants associated with the genetic susceptibility to Chronic Beryllium Disease, namely HLA-DP molecules carrying a glutamate at position 69 of the beta chain;
- to present in the areas of the peptides that interact with the T-cell receptor, amino acids of the sequence of the natural peptide that bound in the groove of the HLA molecule during its biosynthesis, named CLIP (class II associated invariant-chain derived peptide), thus not capable to induce an averse immune response.
One of the peptide described here carries at the HLA-DP interactive position P4 of the peptide (named P4) a high affinity amino acid residue (tyrosine), capable to interact deeply with the HLA-DP binding groove in the pocket 4 area, thus capable to block the response of Be-specific T-cells induced by beryllium itself. Consequently this peptide is useful for the specific therapy of the Chronic Beryllium Disease.
On the other hand, peptides that carry at position P4 an amino acid with electron donor characteristics (such as Arginine or Glutamine) are capable to increase the response to beryllium in Beryllium-specific T-cells. Thus, these peptides could be used to identify in vitro the response to beryllium of Beryllium sensitised subjects.

Innovative Aspects:
The finding in the present invention has potential implication both for the diagnosis and the treatment of berylliosis.
The design of presentation-enhancing peptides capable of increasing T-cell activation signals may determine the implementation of diagnostic tests for the diagnosis of beryllium hypersensitivity.
With regard to berylliosis treatment, which today relies upon the use of corticosteroids and, eventually, lung transplantation, these data suggest that blocking peptides could be designed that, as the glatiramer acetate (named also copaxone or cop-1) in multiple sclerosis, and Fel d1 and PLA on the cat and bee venom allergy, respectively could be tried for their potential ability to block or anergise T-cell reaction in vivo. Short synthetic peptides are a class of components that can be produced in large amounts with relatively small costs, and with respect to biological derived materials (e.g. recombinant proteins) are more stable and less costly.