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Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung

An autoimmune and disease technology, applied in the fields of disease diagnosis, drug combination, analysis of materials, etc., can solve problems such as difficult diagnosis and treatment, unknown potential etiology, etc.

Active Publication Date: 2009-02-25
INDIANA UNIV RES & TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many diseases and conditions, such as idiopathic pulmonary fibrosis (IPF), that are difficult to diagnose and treat, and the underlying cause of these conditions is unknown, requiring more efforts to diagnose and treat

Method used

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  • Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung
  • Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung
  • Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0080] An unexpected result of Example 2 was that patients diagnosed with or at risk of developing IPF could be treated prior to transplantation by restoring or enhancing self-tolerance to col(V). One embodiment is a method of treating IPF by enhancing the patient's response to collagen by oral therapy (Yasufuku et al. 2001; Yasufuku et al., 2002) into the lung space or by administering col(V) based on a desensitization strategy with a designed dosing regimen. Tolerance of proteins including but not limited to type V collagen and antigenic components and variants thereof.

[0081] Another embodiment is an antibody-based assay for the diagnosis and monitoring of diseases including autoimmune responses.

[0082] According to some embodiments, detecting the presence of collagen antibodies can be accomplished with any immunoassay procedure (eg, ELISA). Standard immunoassay textbooks can be found for numerous immunoassay procedures including, but not limited to, noncompetitive sin...

Embodiment 1

[0094] To determine whether patients after lung transplantation also develop autoimmunity specific to type V collagen, we performed a delayed-type hypersensitivity (DTH) assay using leukocytes from eight lung transplants and three different collagens recipient and 5 kidney transplant recipients with pulmonary hemorrhagic nephritic syndrome, an autoimmune disease of type V collagen (col). Such as image 3 As shown in column A, T cells from lung transplant recipients responded to col(V) but not to col(IV) or col(II), whereas T cells from patients with pulmonary hemorrhagic nephritic syndrome responded to col(IV ) had a significantly higher DTH response, but no response to col(V) or col(II). This important finding suggests that lung transplant patients have anti-collagen V autoimmunity.

[0095] We next determined whether an anti-collagen V autoimmune response could be seen in any patient awaiting lung transplantation and, if so, reflects a pre-existing condition that leads to ...

Embodiment 3

[0121]Microbead Assay for Detection of Humoral or Antibody-Mediated Anti-V Collagen Immune Responses. This method is used to detect antibodies to collagen V in the serum and / or lung lavage fluid of patients with autoimmune reactions to collagen V. The method also provides Type V collagen coated microbeads along with other necessary reagents. Serum and / or lung lavage fluid, and common reagents such as PBS may be provided to the end user, or these reagents may be assembled into a kit, to perform the assay. In short, a typical analysis is as follows:

[0122] 1) Streptavidin-coated microbeads (5um, binding capacity 10-20ug / 1×10 / 7 microbeads (Polyscience, Warrington, PA)) were washed twice with sterilized PBS. Microbeads (1×10 / 7) and 40ug human type V collagen were suspended in 100ul PBS and incubated at 4°C for 60 minutes.

[0123] 2) A 20um rabbit anti-human collagen type V antibody (bioten) (Abeam, Cambridge, MA) was used to prepare a positive control following the same proc...

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Abstract

Various embodiments include methods for diagnosing and treating medical conditions that involve an autoimmune response to connective tissue such as collagen found in organs such as the lung. In one method pulmonary disease and disorders such as Idiopathic Pulmonary Fibrosis (IPF) are diagnosed by analyzing fluid or tissue samples obtained from a patient for evidence of an autoimmune response to various types of collagen including, for example, Type V. One type of assay for evidence of an autoimmune response to Type V collagen comprises the steps of obtaining a fluid or tissue sample from a patient, contacting at least a portion of the sample with antigen to anti-Type V collagen antibody and monitoring the mixture of sample and antigen for changes indicative of the presence of anti-Type V collagen in the sample. Another embodiment includes treating pulmonary diseases such as IPF by administering a therapeutically effective dose of epitopes of various collagens including Type V collagen.

Description

[0001] priority statement [0002] This application claims the benefit of US Provisional Patent Application Serial No. 60 / 759,195, filed January 13, 2006, which is hereby incorporated by reference in its entirety. [0003] Statement of Government Funding [0004] The US Government may have certain rights in this invention under Federal Grant No. HL60797 from the National Institutes of Health (NIH). technical field [0005] Various embodiments relate generally to the detection and treatment of pulmonary disease, some aspects include identifying evidence of an autoimmune response to pulmonary connective tissue, such as type V collagen, and other aspects include by administering to a patient a therapeutically effective amount of collagen and collagen-like proteins Molecules to modulate a patient's immune response to collagen by making the patient tolerant to, for example, type V collagen. Background technique [0006] The pathology of the autoimmune response is well understoo...

Claims

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Application Information

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IPC IPC(8): G01N33/00G01N33/566G01N33/567
CPCG01N33/564G01N2800/12G01N33/6887A61P11/00A61P37/06
Inventor D·S·威尔克斯M·J·克莱门兹
Owner INDIANA UNIV RES & TECH CORP
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