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US 11,041,005 B2Granted
Methods for detecting autoantibodies against a GABA(A) receptor alpha 1 subunit and/or beta 3 subunit in autoimmune seizure and/or encephalitis
AssigneesInstitut D'Investigaciones BiomèDiques August Pi I Sunyer, Institució Catalana De Recerca I Estudis AvançAts
InventorJosep Dalmau
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Abstract
The present invention provides a use of a GABA(A)R, GABA(A)R fragment, or homolog thereof or a cell expressing the GABA(A)R, GABA(A)R fragment, or homolog thereof for the prognosis, diagnosis or treatment of an autoimmune disease in a subject, methods of prognosticating, diagnosing or treating an autoimmune disease, an autoantibody binding to a GABA(A)R, GABA(A)R fragment, or homolog thereof, a method for isolating an antibody binding to a GABA(A)R, GABA(A)R fragment, or homolog thereof, and a test kit, pharmaceutical composition and medical or diagnostic device comprising a GABA(A)R, GABA(A)R fragment, or homolog thereof.
Claims10
A method for prognosticating or diagnosing an autoimmune disease, the method comprising:
- a) bringing a liquid sample isolated from a subject suspected of comprising an autoantibody into contact with
- (i) a human or rat gamma-aminobutyric acid-A receptor (GABA(A)R) alpha 1 subunit linked to a reporter-molecule or to a solid phase,
- (ii) a human or rat GABA(A)R beta 3 subunit linked to a reporter-molecule or to a solid phase,
- (iii) a GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2 linked to a reporter-molecule or to a solid phase, or
- (iv) a cell linked to a reporter-molecule or to a solid phase and expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2,
- b) detecting the presence of the binding of the autoantibody to
- (i) the human or rat GABA(A)R alpha 1 subunit linked to a reporter-molecule or to a solid phase,
- (ii) the human or rat GABA(A)R beta 3 subunit linked to a reporter-molecule or to a solid phase,
- (iii) the GABA(A)R having the sequence of SEQ ID NOs:
- 1 or 2 or the variant of SEQ ID NO:
- 2 linked to a reporter-molecule or to a solid phase, or
- (iv) the cell linked to a reporter-molecule or to a solid phase,
- c) subsequent to detecting the presence of the binding, taking blood from the subject,
- d) contacting the blood with
- a pharmaceutical composition comprising
- (i) the human or rat GABA(A)R alpha 1 subunit,
- (ii) the human or rat GABA(A)R beta 3 subunit,
- (iii) the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2, or
- (iv) the cell expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2, or
- a medical device coated with at least one of
- (i) the human or rat GABA(A)R alpha 1 subunit,
- (ii) the human or rat GABA(A)R beta 3 subunit,
- (iii) the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2, or
- (iv) the cell expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- I or 2, and
- e) readministering the contacted blood from step d) to the subject,
- wherein said autoimmune disease is at least one disease selected from the group consisting of seizure, encephalitis and a combination thereof, and
- said liquid sample is at least one liquid sample selected from the group consisting of serum and cerebrospinal fluid (CSF).
30 more elements
A method comprising:
- obtaining at least one liquid sample from a subject having an autoimmune disease, wherein the at least one liquid sample is selected from the group consisting of serum and cerebrospinal fluid (CSF);
- contacting the at least one liquid sample from the subject with
- (i) a human or rat gamma-aminobutyric acid-A receptor (GABA(A)R) alpha 1 subunit linked to a reporter-molecule or to a solid phase,
- (ii) a human or rat GABA(A)R beta 3 subunit linked to a reporter-molecule or to a solid phase,
- (iii) a GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2 linked to a reporter-molecule or a solid phase, or
- (iv) a cell linked to a reporter-molecule or to a solid phase and expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2, and
- subsequently,
- when the at least one liquid sample is cerebrospinal fluid (CSF), detecting the presence of the binding of an autoantibody to
- (i) the human or rat GABA(A)R alpha 1 subunit linked to a reporter-molecule or to a solid phase,
- (ii) the human or rat GABA(A)R beta 3 subunit linked to a reporter-molecule or to a solid phase,
- (iii) the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2 linked to a reporter-molecule or a solid phase, or
- (iv) the cell linked to a reporter-molecule or to a solid phase and expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2, or
- when the at least one liquid sample is serum, determining an antibody titer of an autoantibody to the GABA(A)R wherein the autoantibody is detectable in a serial dilution of at least 1:160 of the serum of the at least one liquid sample and detecting the presence of the binding of the autoantibody to
- (i) the human or rat GABA(A)R alpha 1 subunit linked to a reporter-molecule or to a solid phase,
- (ii) the human or rat GABA(A)R beta 3 subunit linked to a reporter-molecule or to a solid phase,
- (iii) the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2 linked to a reporter-molecule or to a solid phase, or
- (iv) the cell linked to a reporter-molecule or to a solid phase and expressing the human or rat GABA(A)R alpha 1 subunit, the human or rat GABA(A)R beta 3 subunit, or the GABA(A)R having the sequence of SEQ ID NO:
- 1 or 2,
- wherein said autoimmune disease is at least one disease selected from the group consisting of seizure, encephalitis and a combination thereof.
21 more elements
A method of detecting an autoantibody to gamma-aminobutyric acid-A receptor (GABA(A)R) in a subject, the method comprising:
- obtaining a bodily fluid sample from the subject, the subject having an autoimmune disease selected from the group consisting of encephalitis, seizure and a combination thereof, and
- detecting whether the GABA(A)R autoantibody is present in said body fluid by contacting said bodily fluid with live or fixed cells in which human or rat GABA(A)R alpha 1 subunit and human or rat GABA(A)R beta 3 subunit are coexpressed, and detecting the presence of the binding between the autoantibody to the human or rat GABA(A)R alpha 1 subunit and the human or rat GABA(A)R beta 3 subunit.
Dependencies are inferred from the claim text.