Week 8: Personalised medicine II
Diagnostic and personalised therapy: MTX
Educated guess = by knowing the pathway we can give a good shot at finding a new
biomarker.
MTX = methotrexate = acts like folic acids → inhibits purine and pyrilamine synthesis. This
results in an anti-inflammentory response.
In RA there are patients that are non-responders on MTX. How to find these? → need to
develop a prediction model.
Development of a test for the non-responders in MTX:
● BMI = body mass index
● HAQ = health assessment questionnaire
● ESR = Erythrocyte sedimentation rate
● TJC28 = number of tender joints affected out of 28 joints
● DMARD/corticosteroid use = YES or NO
● Smoking = never/former or current
Step 1: biomarker identification: Use PBMC (lymphocytes and monocytes)
Step 2: test development: Choosing the matrix & use the LC-MS system for output.
Step 3: clinical validation: MTX polyglutamates in RB are associated with lower disease
activity in RA patients.
Step 4: Implantation
Advances in hormone measurements
>Competitive immunoassay: concentration of the hormone is unknown. The antibodies either
bind the labled hormone or the endogenous hormone. The more labelled hormone is formed
→ the less endogenous hormone is formed.
>Sandwich immunoassay: put a serum in over the antibodies. The endogenous hormone will
match the antibodies. Then, labbled antibodies are put in, also binding to the endogenous
hormone. The more labelled antibodies, the more endogenous hormone in the serum.
LC-MSMS = liquid chromatography + mass spectrometry
>liquid chromatography (LC): serum moves with high pressure through the colon. Via
different binding affinity, the molecules move over different times out of the colon.
>mass spectrometry (MS): molecules are ionised to the gas phase. Via electric field to
magnetic field → separated by their mass. This MS is done another time to detect very
specific molecules. Measure the intensity of the molecules.
Congenital adrenal hyperplasia:
Diagnostic and personalised therapy: MTX
Educated guess = by knowing the pathway we can give a good shot at finding a new
biomarker.
MTX = methotrexate = acts like folic acids → inhibits purine and pyrilamine synthesis. This
results in an anti-inflammentory response.
In RA there are patients that are non-responders on MTX. How to find these? → need to
develop a prediction model.
Development of a test for the non-responders in MTX:
● BMI = body mass index
● HAQ = health assessment questionnaire
● ESR = Erythrocyte sedimentation rate
● TJC28 = number of tender joints affected out of 28 joints
● DMARD/corticosteroid use = YES or NO
● Smoking = never/former or current
Step 1: biomarker identification: Use PBMC (lymphocytes and monocytes)
Step 2: test development: Choosing the matrix & use the LC-MS system for output.
Step 3: clinical validation: MTX polyglutamates in RB are associated with lower disease
activity in RA patients.
Step 4: Implantation
Advances in hormone measurements
>Competitive immunoassay: concentration of the hormone is unknown. The antibodies either
bind the labled hormone or the endogenous hormone. The more labelled hormone is formed
→ the less endogenous hormone is formed.
>Sandwich immunoassay: put a serum in over the antibodies. The endogenous hormone will
match the antibodies. Then, labbled antibodies are put in, also binding to the endogenous
hormone. The more labelled antibodies, the more endogenous hormone in the serum.
LC-MSMS = liquid chromatography + mass spectrometry
>liquid chromatography (LC): serum moves with high pressure through the colon. Via
different binding affinity, the molecules move over different times out of the colon.
>mass spectrometry (MS): molecules are ionised to the gas phase. Via electric field to
magnetic field → separated by their mass. This MS is done another time to detect very
specific molecules. Measure the intensity of the molecules.
Congenital adrenal hyperplasia:
