Newborn screening for primary immunodeficiency, cystinosis, and Wilson disease

Abstract

Newborn screening for primary immunodeficiency, cystinosis, and Wilson disease is described. Newborn screening can detect these conditions from dried blood spots that are already routinely collected at birth. Early detection of these conditions will greatly improve patient outcomes because each of these conditions can be fatal once symptoms develop.

Claims

1. Use of an antibody or antigen-binding fragment thereof that binds to a characteristic peptide of ATP7B in preparing a kit for screening a subject for a disease, wherein the disease comprises Wilson's disease (WD), The antibody or antigen-binding fragment thereof that binds to the ATP7B characteristic peptide comprises: a VH domain comprising CDR1 of SEQ ID NO: 57, CDR2 of SEQ ID NO: 58, and CDR3 of SEQ ID NO: 59; and a VL domain comprising CDR1 of SEQ ID NO: 60, CDR2 of SEQ ID NO: 61, and CDR3 of SEQ ID NO: 62, The sequence of the ATP7B characteristic peptide is SEQ ID NO: 11 or 21.

2. The use according to claim 1, wherein the disease further comprises Wiskott-Aldrich syndrome (WAS), and the kit further comprises an antibody or antigen-binding fragment thereof that binds to a first WASp characteristic peptide for screening for WAS, comprising: a VH domain comprising CDR1 of SEQ ID NO: 28, CDR2 of SEQ ID NO: 29, and CDR3 of SEQ ID NO: 30; and a VL domain comprising: CDR1 of SEQ ID NO: 31, CDR2 of SEQ ID NO: 32, and CDR3 of SEQ ID NO: 33; and / or The disease further includes X-linked agammaglobulinemia XLA, and the kit further includes an antibody or antigen-binding fragment thereof that binds to a first BTK characteristic peptide for screening for XLA, comprising: a VH domain comprising CDR1 of SEQ ID NO: 34, CDR2 of SEQ ID NO: 35, and CDR3 of sequence GDI; and a VL domain comprising: CDR1 of SEQ ID NO: 36, CDR2 of SEQ ID NO: 37, and CDR3 of SEQ ID NO:

38.

3. The use of claim 2, wherein the antibody or antigen-binding fragment thereof that binds to the first WASp characteristic peptide comprises: (i) a VH domain having at least 90% sequence identity to SEQ ID NO: 65 and a VL domain having at least 90% sequence identity to SEQ ID NO: 66; or (ii) a heavy chain having at least 90% sequence identity to SEQ ID NO: 86 and a light chain having at least 90% sequence identity to SEQ ID NO:

91.

4. The method of claim 2, wherein the antibody or antigen-binding fragment thereof that binds to the first BTK characteristic peptide comprises: (i) a VH domain having at least 90% sequence identity to SEQ ID NO: 67 and a VL domain having at least 90% sequence identity to SEQ ID NO: 68; or (ii) a heavy chain having at least 90% sequence identity to SEQ ID NO: 96 and a light chain having at least 90% sequence identity to SEQ ID NO:

101.

5. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to the ATP7B characteristic peptide comprises: (i) a VH domain having at least 90% sequence identity to SEQ ID NO: 75 and a VL domain having at least 90% sequence identity to SEQ ID NO: 76; or (ii) a heavy chain having at least 90% sequence identity to SEQ ID NO: 136 and a light chain having at least 90% sequence identity to SEQ ID NO:

141.

6. An isolated antibody or antigen-binding fragment thereof, comprising: (a) a VH domain and a VL domain, wherein the VH domain comprises CDR1 of SEQ ID NO: 57, CDR2 of SEQ ID NO: 58, and CDR3 of SEQ ID NO: 59, and the VL domain comprises CDR1 of SEQ ID NO: 60, CDR2 of SEQ ID NO: 61, and CDR3 of SEQ ID NO:

62.

7. The isolated antibody or antigen-binding fragment thereof according to claim 6, (a) wherein the VH domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 75 and an amino acid sequence having at least 90% sequence identity to the sequence shown in SEQ ID NO:

76.

8. The isolated antibody or antigen-binding fragment thereof according to claim 7, wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain and a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 90% sequence identity to the sequence shown in SEQ ID NO: 136; and the light chain comprises an amino acid sequence having at least 90% sequence identity to the sequence shown in SEQ ID NO:

141.

9. A kit comprising: (i) an antibody or antigen-binding fragment thereof that binds to the ATP7B peptide of SEQ ID NO: 11 or 21, comprising: a VH domain comprising CDR1 of SEQ ID NO: 57, CDR2 of SEQ ID NO: 58, and CDR3 of SEQ ID NO: 59; and a VL domain comprising CDR1 of SEQ ID NO: 60, CDR2 of SEQ ID NO: 61, and CDR3 of SEQ ID NO: 62; and optionally: (ii) a reference signature peptide, the reference signature peptide comprising: The ATP7B peptide shown in SEQ ID NO: 10; ATP7B peptide shown in SEQ ID NO:11; ATP7B peptide shown in SEQ ID NO:16; The ATP7B peptide shown in SEQ ID NO: 17; ATP7B peptide of WD shown in SEQ ID NO:18; The ATP7B peptide shown in SEQ ID NO: 19; The ATP7B peptide shown in SEQ ID NO: 20; and / or ATP7B peptide shown in SEQ ID NO: 21, optionally The kit further comprises one or more of a filter paper card, a punching tool, a digestion enzyme, a digestion buffer, a solid support of the antibody or its antigen-binding fragment, and an elution buffer, or the reference signature peptide is isotope-labeled, or the antibody or its antigen-binding fragment is attached to magnetic beads.

10. The kit of claim 9, further comprising: (i) an antibody or antigen-binding fragment thereof that binds to a WASp characteristic peptide of WAS of SEQ ID NO: 2, comprising: a VH domain comprising CDR1 of SEQ ID NO: 28, CDR2 of SEQ ID NO: 29, and CDR3 of SEQ ID NO: 30; and a VL domain comprising: CDR1 of SEQ ID NO: 31, CDR2 of SEQ ID NO: 32, and CDR3 of SEQ ID NO: 33; and / or An antibody or antigen-binding fragment thereof that binds to the BTK characteristic peptide of XLA of SEQ ID NO: 4, comprising: a VH domain comprising CDR1 of SEQ ID NO: 34, CDR2 of SEQ ID NO: 35, and CDR3 of sequence GDI; and a VL domain comprising: CDR1 of SEQ ID NO: 36, CDR2 of SEQ ID NO: 37, and CDR3 of SEQ ID NO: 38; and optionally: (ii) a reference signature peptide, the reference signature peptide comprising: WASp peptide of WAS shown in SEQ ID NO: 2; WASp peptide of WAS shown in SEQ ID NO: 3; The BTK peptide of XLA shown in SEQ ID NO: 4; and / or The BTK peptide of XLA shown in SEQ ID NO:5.

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