HLA-B*27
Ankylosing spondylitis / axial SpA
~90% of patients in many European cohorts; misfolding and IL-23/IL-17 axis.
Layer 06 · Dynamics
Where it happens, and what it costs
Immunology is tissue-specific and metabolically expensive. The same cell behaves differently in a lymph node and a tumour, and each cell state runs on a different fuel programme.
12COMPARTMENTS
7FUEL PROGRAMMES
10ALLELES
The infection simulator now has its own layer: 05 · System simulator.
Tissue immunology
Twelve compartments, what they do for immunity, and the disease that follows when they fail. Select one to open its dossier.
Immunometabolism
Why a T cell cannot divide and stay quiescent on the same fuel, and how the tumour microenvironment starves the wrong cell. Select a cell state.
Immunogenetics
Alleles that change the threshold, not the mechanism — and one that changed how we screen before prescribing.
HLA-DRB1 shared epitope (*04:01, *04:04, *01:01)
ACPA-positive RA
Preferential presentation of citrullinated peptides.
HLA-DQ2 / DQ8
Coeliac disease; type 1 diabetes
Deamidated gliadin binds DQ2/DQ8 with high affinity.
HLA-B*57:01
Abacavir hypersensitivity
Drug alters the peptide groove; mandatory pre-prescription screening.
HLA-B*15:02
Carbamazepine SJS/TEN
Screen in people of Han Chinese/Southeast Asian ancestry.
HLA-B*58:01
Allopurinol SJS/TEN/DRESS
Screening recommended in high-prevalence ancestries.
TYK2 P1104A
Protection from RA, SLE, psoriasis; TB susceptibility (homozygous)
Human genetics validated the deucravacitinib target.
PTPN22 R620W
RA, T1D, SLE, Graves
Alters TCR/BCR signalling thresholds.
IL23R R381Q
Protection from IBD and psoriasis
Loss-of-function supports targeting IL-23.
NOD2 variants
Ileal Crohn disease
Impaired bacterial sensing and Paneth-cell function.