Systems and methods for rheumatoid arthritis biomarker detection
Embodiments provide for devices and methods of use for detecting one or more biomarkers of rheumatic disease in a subject. In an example, a method includes detecting citrullinated human serum albumin (HSA) in a biological sample via obtaining the biological sample from a subject, applying the biological sample to a lateral flow device under conditions sufficient for formation of an immunocomplex comprising anti-HSA antibody coupled to citrullinated HSA that is in turn coupled to anti-citrullinated HSA autoantibody, determining a quantity of the immunocomplex, and managing rheumatic disease associated with the subject. In this way, rheumatic disease may be effectively managed based at least in part on amounts of citrullinated HSA detected via rapid point-of-care test methodology.
1. A method of detecting and quantifying anti-citrullinated human serum albumin (HSA) autoantibody in a biological sample, comprising:
obtaining the biological sample from a subject;
applying the biological sample to a lateral flow device, wherein the lateral flow device comprises anti-human IgA, IgG, and IgM antibodies affixed to a surface, under conditions sufficient for formation of an immunocomplex, wherein the immunocomplex comprises anti-citrullinated HSA autoantibody bound to citrullinated HSA;
applying to the lateral flow device an anti-HSA antibody coupled to a detectable label, wherein the anti-HSA antibody is capable of binding the citrullinated HSA in the immunocomplex; and
detecting a quantity of the immunocomplex to determine a quantity of anti-citrullinated HSA autoantibody.
2. The method of claim 1 , wherein the biological sample is serum or plasma.
3. The method of claim 1 , wherein the detectable label is a colloidal gold particle.
4. The method of claim 1 , wherein detecting the quantity of the immunocomplex is via a reader configured with an image analysis system; and
wherein detecting the quantity of the immunocomplex further comprises quantifying relative amounts of the immunocomplex to a control complex.
5. The method of claim 4 , wherein the control complex comprises streptavidin coupled to a detectable label.
6. The method of claim 5 , wherein the detectable label of the control complex is a colloidal gold particle.
7. The method of claim 5 , wherein the streptavidin coupled to the detectable label is captured via the lateral flow device by biotin-coupled bovine serum albumin (BSA).
8. A method of detecting and quantifying a first biomarker and at least a second biomarker associated with rheumatic disease in a biological sample of a subject, comprising:
obtaining the biological sample from the subject;
applying the biological sample to a lateral flow device, wherein the lateral flow device comprises anti-human IgA, IgG, and IgM affixed to a surface, under conditions sufficient for formation of a first immunocomplex comprising at least the first biomarker and a first labeled biomolecule capable of recognizing the first biomarker, wherein the first biomarker is anti-citrullinated human serum albumin (HSA) autoantibody, and the first labeled biomolecule is anti-HSA antibody coupled to a detectable label, and
wherein the second biomarker is one of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibody (ACCP), or anti-citrullinated peptide autoantibody (ACPA); and
detecting a quantity of each of the first immunocomplex and the second biomarker.
9. The method of claim 8 , further comprising a second immunocomplex comprising at least the second biomarker and a second labeled biomolecule capable of recognizing the second biomarker, and wherein detecting the second biomarker comprises detecting the second immunocomplex.