Use of mycobacterium avium paratuberculosis peptides to diagnose type 1 diabetes
AssigneeUniversita Degli Studi Di Sassari
InventorsLeonardo Antonio Sechi, Roberto Mallone
Life of this patent
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Abstract
The present invention concerns antibodies recognizing Mycobacterium avium paratuberculosis epitopes able to cross-reacting with the beta-cell antigen ZnT8 to be used as early biomarkers of type 1 diabetes, epitopes for in vitro prognostic and diagnostic methods suitable to reveal a risk to develop type 1 diabetes, therapies for the prevention of T1D by avoiding, controlling or monitoring Mycobacterium paratuberculosis infection.
Claims39
A method for diagnosing an individual who is susceptible to or who is developing type I diabetes, the method comprising
- contacting a sample from the individual with at least one isolated peptide belonging to MAP3865c or ZnT8, or at least one isolated antibody specific for said at least one peptide, in an in vitro test
- wherein said at least one peptide is chosen from the group consisting of MAP3865c125-133 having sequence MIAVALAGL (SEQ ID NO:1), MAP3865c133-141 having sequence LAANFVVAL (SEQ ID NO:2), MAP3865c121-127 having sequence PGVPMIA (SEQ ID NO:13), MAP3865c131-137 having sequence AGLAANF (SEQ ID NO:14), MAP3865c246-252 having sequence LSPGKDM (SEQ ID NO:9), MAP3865c256-262 having sequence HLISTGD (SEQ ID NO:10), MAP3865c261-267 having sequence GDSARVL (SEQ ID NO:11), MAP3865c281-287 having sequence HATVQID (SEQ ID NO:12), ZnT8178-186 having sequence MIIVSSCAV (SEQ ID NO:3), ZnT8186-194 having sequence VAANIVLTV (SEQ ID NO:4),
- wherein the at least one isolated peptide belonging to MPA 3865c or the at least one isolated antibody specific for said at least one peptide are detected as biomarker for diagnosing the individual who is susceptible to or who is developing type I diabetes.
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A method for in vitro diagnosing a subject who is susceptible to or who is developing type I diabetes, said method comprising:
- a) detecting and quantifying, in a blood sample of said subject, antibodies specific for at least one peptide belonging to MAP3865c or ZnT8, to obtain detected and quantified values, wherein said at least one peptide is chosen from the group consisting of MAP3865c125-133 having sequence MIAVALAGL (SEQ ID NO:1), MAP3865c133-141 having sequence LAANFVVAL (SEQ ID NO:2), MAP3865c121-127 having sequence PGVPMIA (SEQ ID NO:13), MAP3865c131-137 having sequence AGLAANF (SEQ ID NO:14), MAP3865c246-252 having sequence LSPGKDM (SEQ ID NO:9), MAP3865c256-262 having sequence HLISTGD (SEQ ID NO:10), MAP3865c261-267 having sequence GDSARVL SEQ ID NO:11 MAP3865c281-287 having sequence HATVQID (SEQ ID NO:12), ZnT8178-186 having sequence MIIVSSCAV (SEQ ID NO:3), ZnT8186-194 having sequence VAANIVLTV (SEQ ID NO:4);
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- b) comparing the detected and quantified values of step a) with those of an healthy control.
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A method for in vitro diagnosing a subject who is susceptible to or who is developing type I diabetes,
- said method comprising incubating a blood sample comprising lymphocytes from said subject in the presence of
- at least one peptide belonging to MAP3865c, said at least one MAP3865c peptide having an homology of at least 50% in comparison to a corresponding peptide belonging to human ZnT8 sequence after optimal alignment;
- and/or in the presence of at least one peptide belonging to ZnT8 sequence from aminoacid 174 to aminoacid 194, said ZnT8 peptide having an homology of at least 80% in comparison to a corresponding peptide belonging to MAP3865c from aminoacid 121 to aminoacid 141,
- the incubating performed for a time and under conditions sufficient to stimulate the lymphocytes to produce an effector molecule, wherein the presence or level of the effector molecule is indicative of the lymphocytes derived from a subject susceptible to or who is developing type I diabetes
- wherein said at least one peptide belonging to MAP3865c is chosen from the group consisting of MAP3865c125-133 having sequence MIAVALAGL (SEQ ID NO:1), MAP3865c133-141 having sequence LAANFVVAL (SEQ ID NO:2), MAP3865c121-127 having sequence PGVPMIA (SEQ ID NO:13), MAP3865c131-137 having sequence AGLAANF (SEQ ID NO:14), MAP3865c246-252 having sequence LSPGKDM (SEQ ID NO:9), MAP3865c256-262 having sequence HLISTGD SEQ ID NO:10 MAP3865c261-267 having sequence GDSARVL (SEQ ID NO:11), MAP3865c281-287 having sequence HATVQID (SEQ ID NO:12), ZnT8178-186 having sequence MIIVSSCAV (SEQ ID NO:3), ZnT8186-194 having sequence VAANIVLTV (SEQ ID NO:4).
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An isolated peptide belonging to MAP3865c, said MAP3865c peptide having an homology of at least 50% in comparison to a corresponding peptide belonging to human ZnT8 sequence after optimal alignment;
- or belonging to ZnT8 sequence from aminoacid 174 to aminoacid 194, said ZnT8 peptide having an homology of at least 80% in comparison to a corresponding peptide belonging to MAP3865c from aminoacid 121 to aminoacid 141,
- wherein said isolated peptide belongs to MAP3865c from aminoacid 121 to aminoacid 141,
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A method for prevention and treatment of type I diabetes, in an individual, the method comprising
- administering to the individual an effective amount of one or more anti Mycobacterium avium paratuberculosis drugs.
Dependencies are inferred from the claim text.