Diagnostic methods for the detection of autism spectrum disorder
View Patent ↗The present invention provides methods of identifying markers indicative of the risk of developing a neurodevelopmental disorder caused in part by antibody- or autoantibody-mediated damage of neural tissue, including autism spectrum disorder (ASD). The invention further provides methods of diagnosing whether an individual has a neurodevelopmental disorder, including an ASD, and methods for determining the risk that a mother's future offspring will develop an a neurodevelopmental disorder, including an ASD.
1. A method of diagnosing an autism spectrum disorder (ASD) in an individual, the method comprising:
(a) contacting a first fluid tissue sample from the individual with brain extracts comprising at least one brain region selected from the group consisting of cerebellum, amygdala and orbital frontal cortex, wherein the first fluid tissue sample is blood, serum, plasma or cerebrospinal fluid, and wherein the brain extracts are from a non-living primate;
(b) detecting binding of autoantibody from the fluid tissue sample to a neural antigen in the brain extracts, wherein binding of the autoantibody to a neural antigen in the extract of at least one of cerebellum, amygdala or orbital frontal cortex is indicative of an ASD;
(c) contacting a second fluid tissue sample from the individual with a brain section comprising cerebellum from a non-living primate, wherein the second fluid tissue sample is blood, serum, plasma or cerebrospinal fluid; and
(d) detecting a pattern of staining resulting from binding of the autoantibody to the brain section that is indicative of an ASD, wherein the pattern of staining is characterized by scattered intensively stained cells below the Purkinje layer of the cerebellum;
whereby detecting the binding of the autoantibody and detecting the pattern of staining is indicative of the presence of an ASD, thereby diagnosing an ASD in the individual.
2. The method of claim 1 , wherein brain cell types, stained within the brain section in step (d) are selected from the group consisting of granular layer cells, Golgi Type II cells and brain endothelial cells.
3. The method of claim 2 , wherein the staining of brain cells in step (d) is intracytoplasmic and stains the length of the dendrites.
4. The method of claim 1 , wherein the presence of the autoantibody determined in step (b) is determined by an immunoassay.
5. The method of claim 1 , wherein the brain section in step (c) is from a whole brain.
6. The method of claim 1 , wherein the brain extract in step (a) is from a non-human primate brain.
7. The method of claim 1 , wherein the brain section in step (c) is from a non-human primate brain.
8. The method of claim 1 , wherein the brain section in step (c) is a coronal, horizontal or sagittal section.
9. A method of determining an increased risk of an ASD in a mother's future offspring, the method comprising:
(a) contacting a first fluid tissue sample taken from the mother during a prenatal period with brain extracts comprising at least one brain region selected from the group consisting of cerebellum, amygdala and orbital frontal cortex, wherein the first fluid tissue sample is blood, serum, plasma or cerebrospinal fluid, and wherein the brain extracts are from a non-living primate;
(b) detecting binding of antibody from the fluid tissue sample to a neural antigen in the brain extracts, wherein binding of the antibody to a neural antigen in the extract of at least one of cerebellum, amygdala or orbital frontal cortex is indicative of an ASD;
(c) contacting a second fluid tissue sample from the individual with a brain section comprising cerebellum from a non-living primate, wherein the second fluid tissue sample is blood, serum, plasma or cerebrospinal fluid; and
(d) detecting a pattern of staining resulting from the binding of the antibody to the brain section that is indicative of an ASD, wherein the pattern of staining is characterized by scattered intensively stained cells below the Purkinje layer of the cerebellum;
whereby detecting the presence of the antibody and the pattern of staining is indicative of an increased risk of an ASD in the mother's future offspring.
10. The method of claim 9 , wherein brain cell types stained within the brain section in step (d) are selected from the group consisting of granular layer cells, Golgi Type II cells and brain endothelial cells.
11. The method of claim 10 , wherein the staining of brain cells in step (d) is intracytoplasmic and stains the length of the dendrites.
12. The method of claim 9 , wherein the presence of the antibody determined in step (b) is determined by an immunoassay.
13. The method of claim 9 , wherein the brain section in step (c) is from a whole brain.
14. The method of claim 9 , Wherein the brain extract in step (a) is from a non-human primate brain.
15. The method of claim 9 , wherein the brain section in step (c) is from a non-human primate brain.
16. The method of claim 9 , wherein the brain section in step (c) is from a fetal brain.
17. The method of claim 9 , wherein the brain section in step (c) is a coronal, horizontal or sagiffal section.
18. The method of claim 9 , wherein the neural antigen is a fetal neural antigen.