Autoantibody Panel for RA and SLE Diagnosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic methods for autoimmune diseases like Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) rely heavily on nonspecific markers, leading to challenges in early detection and differentiation from other autoimmune diseases, and existing treatments have immunosuppressive side effects.
Innovation Solution
The development of a diagnostic assay that detects autoantibodies against hnRNP-D-like protein and other specific autoantigens, using citrullinated hnRNP-DL polypeptides and other hnRNP polypeptides, along with cyclic citrullinated peptides and the Fc-part of IgG, to identify the presence of autoimmune diseases, particularly RA and SLE, with high diagnostic sensitivity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current diagnostic methods use nonspecific markers like RF and ANA, then the diagnostic coverage is broad, but the diagnostic specificity and ability to differentiate between autoimmune diseases is poor
Solution Approach 1:
The patent segments the diagnostic approach by dividing the panel into specific autoantigen targets (hnRNP-DL, hnRNP-D, hnRNP-A2/B1, citrullinated proteins) rather than using broad nonspecific markers. This segmentation allows differentiation between RA and SLE by detecting disease-specific autoantibody profiles, thereby improving diagnostic specificity while maintaining manageable assay complexity through modular panel design.
Solution Approach 2:
The patent applies local quality by selecting autoantigens with specific pathological relevance to particular autoimmune diseases. For example, citrullinated proteins are locally targeted for RA diagnosis while hnRNP-DL and hnRNP-D are targeted for SLE diagnosis. This localized targeting of specific autoantigen types improves diagnostic precision without requiring comprehensive testing of all possible autoantigens.
2Measurement precision
If current diagnostic methods rely on markers like RF and ANA, then the assays are simple to perform, but the ability to detect early stage disease is limited
Solution Approach 1:
The patent enables preliminary detection of autoimmune disease by identifying specific autoantibody profiles against hnRNP-DL, hnRNP-D, and other autoantigens before classic symptoms manifest. The method detects early pathological changes in the immune response targeting specific nuclear proteins, allowing diagnosis prior to joint damage or organ involvement, thereby reducing diagnosis delay.
Solution Approach 2:
The patent replaces traditional mechanical/clinical assessment methods with a biochemical detection system that measures autoantibody levels against specific autoantigens. This substitution of detection mechanism enables objective quantification of early immune responses that are not detectable by clinical examination alone, improving early detection capability.
3Measurement precision
If current diagnostic methods use traditional markers, then the cost and complexity are low, but the diagnostic sensitivity for specific diseases is insufficient
Solution Approach 1:
The patent achieves universality by designing an autoantibody panel that can diagnose multiple autoimmune diseases (RA, SLE, and other connective tissue diseases) using a single comprehensive assay system. The same panel structure and detection methodology are applied across different disease contexts, improving diagnostic sensitivity for each specific disease while avoiding the need for separate specialized assays for each condition.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach provides a more specific and sensitive diagnostic method for RA and SLE, enabling early detection and differentiation from other autoimmune diseases, with a diagnostic sensitivity of at least 80% and specificity of 96% compared to controls, and potential for predicting disease development in early arthritis patients.
Implementation Method 1
contacting said sample with: i. a citrullinated hnRNP-D-like (hnRNP-DL) polypeptide comprising the sequence of SEQ ID NO:5, and ii. at least one other hnRNP polypeptide... determining whether an antibody is present in said sample that specifically recognizes said citrullinated hnRNP-DL polypeptide
Data Source
Figure 1~4
Figure 5~8
Figure 9~12
AI summary
The present invention pertains to a diagnostic assay for the diagnosis of an autoimmune disease. The present invention provides an improved diagnostic assay for the diagnosis of an autoimmune disease, particularly rheumatoid arthritis (RA) and Systemic Lupus Erythematosus (SLE). In particular the invention pertains to a method of determining in a sample of a subject the presence of two or more antibodies comprising the step of determining whether an antibody is present in a sample that specifically recognizes a hnRNP-DL polypeptide or a fragment thereof or a splice variant thereof and the further step of determining whether at least one further antibody is present in the sample that specifically recognizes a at least one other linRNP polypeptide which is not sequence homologue to said hnRNP-DL polypeptide or fragments thereof or splice variants thereof, and/or said CCP peptide and/or a polypeptide comprising at least the Fc-part of IgG, respectively. The invention also relates to polypeptides, protein sets and antibodies that may be used in such methods and assays and for therapeutic use in RA and SLE patients.