| Reference | Disease | n | Setting | Sample / Cell | Stimulus | Assay | Result |
|---|---|---|---|---|---|---|---|
| (Agostini, 2004 #1839) | MWS | 1 | Ex vivo | Macrophage isolated from a MWS with R260W mutation (from purified monocytes) | X | control: not detectible ↑ (x5-10?) IL-1b | |
| O (LPS) | ↑ (x~1.5) IL-1b | ||||||
| (Rodriguez-Smith, 2017 #1840) | CINCA | 23? | In vivo | blood | X | Bio-Plex multiplex assays (Bio-Rad) | No difference (baseline), not reliable assay라고 |
| CSF | X | No difference (baseline), not reliable assay라고 |
WBC
| Reference | Disease | n | Setting | Sample | Stimulation? | Assay | Result |
|---|---|---|---|---|---|---|---|
| (Han, 2014 #1841) | P-oind 의 대부분이 cinca 라기는 히는데. | In vivo | Blood and CSF | X | |||
| (Rodriguez-Smith, 2017 #1840) | CINCA | HC 7, patients (bl2, not cr8, cr8) | In vivo | CSF | X | Flow cytometry → imunophenotypine |
Fig 4. 여기서는 monote 는 CSF만 증가, , basophil도 csf 증가, B cell 둘다 증가, myeloid cell 둘다증가, plasma dendritic cell 도 둘다 증가, , granulocyte 둘 다 안 증가 Complete clinical remission was defined by the following criteria: erythrocyte sedimentation rate (ESR) ... mm/hour, C-reactive protein (CRP) ≤0.5 mg/dl, CSF white blood cell (WBC) count ≤5 cells/mm³, and protein ... mg/dl |
Dx
f. Dx criteria
|
(Kuemmerle-Deschner, 2017 #1824) Important used in Inzomelid trial (Welzel, 2021 #1834) |
the presence of raised inflammatory markers (CRP or SAA) plus at least two of six CAPS-typical signs or symptoms including (1) urticaria-like rash, (2) cold-triggered episodes, (3) sensorineural hearing loss, (4) musculoskeletal symptoms of arthralgia/arthritis/myalgia, (5) chronic aseptic meningitis and (6) skeletal abnormalities of epiphyseal overgrowth/frontal bossing is highly likely to confirm the diagnosis of CAPS. Figure 1. Diagnostic approach to CAPS (kept as evidence in `body_r02_c01.jpg` / `body_r02_c02.jpg`). Caption: WBC, whole blood count; CRP, c reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; HF-PTA, high frequency pure tone audiogram; MRI, magnet resonance imaging; CSF, cerebrospinal fluid; ICP, intracranial pressure; PID, primary immune deficiency; AIDAI, autoinflammatory disease activity index; S100, S 100 proteins (S100A12, S100A8/A9); VUS, variant of uncertain significance. Bold format and grey background indicate headings. |
g. Genetic testing usually detects de-novo NLRP3 mutations → In the absence of a positive standard genetic test, NLRP3 somatic mosaism should be investigated
h.
ARP
| C-reactive protein (CRP) | Serum amyloid A (SAA) | ESR (Erythrocyte sedimentation rate) | |
|---|---|---|---|
| (ring-shaped) pentameric protein found in, | a family of apolipoproteins associated with high-density lipoprotein (HDL) | the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over the period of one hour. Fibrinogen (pro-semintation), RBCs negative charge (anti-semimentation), Fibrinogen is from liver | |
| Location | blood plasma | ||
| Origin | Liver hepatocyte | Liver | |
| The plasma half-life of CRPs | 19 hours, 다른 데선 half-life of 6-8 hours) | Fibrinogen half life: one w 이래서 acute 염증에서는 열등한 marker | |
| Phase of inflammation | acute-phase | ||
| MOA |
(Systemic) IL-6 secretion by macrophages, adipocytes and T cells → (liver) ↑ CRP 생산 Other inflammatory mediators that can increase CRP are TGF β 1, and TNF alpha. | (systemic) ↑ proinflammatory cytokines IL-1, IL-6, and TNF-α → ↑ liver 에서 SAA 생산 | (systemic) ↑ proinflammatory cytokines IL-1, IL-6, and TNF-α → (liver) ↑ fibrinogen 생산 → ↑ fibrinogen → RBCs stick to each other → ↑ ESR |
| Function | bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) → activate the complement system via C1q.[5] | transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix. | |
| measurement methods | |||
| normal |
| <10 mg/L | Newborn: 0 to 2 mm/h Neonatal to puberty: 3 to ... Male: ≤ age/2 ; Female: (age+10)/2.[2] (Unit: mm/hour).[2] |
| acute inflammation | >500 mg/L | the concentration can rise to 1 mg/mL or even higher. | ESR begins to rise at 24 to 48 hours after the onset of acute self-limited inflammation |
| chronic inflammation | 2-10 mg/L | ||
| CAPS | 17 mg/L {Kim, 2018 #1822}, 19.93 (10.50) mg/L (Canakinumab p3) | 71.09 (14.35) mg/L (Canakinumab p3) | 76.8 mm/h {Kim, 2018 #18...} |
Sx
| Mild | Severe | Affecting prognosis | In Dx criteria? | Responsive to current Tx? | MOA | PD BM | DR BM | |
|---|---|---|---|---|---|---|---|---|
| morning headache (indicative of chronic meningitis), | seizures, hydrocephalus or mental retardation | O | O | 아마 x: BBB | Meningitis → IICP → brain atrophy | CSF NLRP3 /ASC/ CASP1 IL-1b, CSF WBC | xiv) ... | |
| papilloedema or aseptic meningitis, Mild total: 26-29% | Severe total: 12% | (monocyte, granucocyte) | xv) | |||||
| conjunctivitis or uveitis, Mild total: ~70%, (in Kim 55.6%) | optic nerve atrophy, cataract, glaucoma, vision. Severe total: 12% (in Kim 0(?)%) | O ((Goldbach-Mansky 2011) permanent damage (band keratopathy, corneal clouding, retinal scarring, optic n atrophy, ↓ (progressive) vision | 아마 x: BRB | Inflammation → infiltrates, or IICP (Since the optic nerve is wrapped in the meninges) → papilledema → optic n swelling (so far reversible) → ↓ vision (this can also be reversible) | CSF NLRP3 /ASC/ CASP1 IL-1b | Ophthalmology examination (ophthalmo...) | ||
| (Kitley, 2010 #1836) in Canakinumab trial, Six patients (46%) had papilledema and a further 2 (15%) had optic disc pallor. MRI brain scan was normal in all patients. | 구분 x: 다 severe겠지. | O (permanent damage) | O | 아마 x: BLB (blood-...) | spread of the infection from the | CSF NLRP3 /ASC/ ... | Audiogram MRI (enh...) |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
top evidence table / Bio-Plex assay note | reads No difference (baseline), not reliable assay라고 for both blood and CSF rows of (Rodriguez-Smith, 2017 #1840). | low confidence on whether assay라고 carries a Korean particle suffix or is truncated. |
WBC table / (Han, 2014 #1841) disease cell | reads P-oind 의 대부분이 cinca 라기는 히는데. with handwritten-style Korean annotation; preserved verbatim. | low confidence on P-oind token (likely an abbreviation for some patient cohort). |
Dx Figure 1 / sub-block text | the diagnostic flowchart contains small-font sub-block text such as Pattern of clinical symptoms (AIDAI, symptom diary), Pattern of laboratory inflammation (SAA, CRP (S100) during flare and in between), Genetic testing (AID panel (Focus NLRP3 gene)); text inside the figure is reproduced from the visible portions in body_r02_c01.jpg / body_r02_c02.jpg and may have low confidence on individual tokens. | low confidence on figure-internal small-font text. |
Sx table / DR BM column | the right-most DR BM column entries are partly clipped; visible content is xiv), xv), Ophthalmology examination (ophthalmo...), Audiogram MRI (enh...). | clipped at right edge; partial. |