Table 2.
Clinical Relevance of Diurnally-Regulated Proteins in Human Plasma
| Clinical Test | Diurnally-Regulated Protein(s) | Clinical Significance | Mean Acrophase (h) ± SD |
|---|---|---|---|
| aPTT | F11; F5; F9; PROC; SERPINC1; FGA | Coagulation status; Bleeding disorders; Liver function monitoring | 4.6 ± 2.3 |
| PT (INR) | F5; FGA | Coagulation status; Liver synthetic function assessment | 5.2 ± 1.1 |
| D-Dimer | FGA | Thrombosis diagnosis; Disseminated intravascular coagulation (DIC) | 4.5 ± – |
| Fibrinogen | FGA | Coagulation status; Acute-phase inflammatory response | 4.5 ± – |
| Albumin | ALB | Nutritional status; Liver function; Chronic illness monitoring | 0.1 ± – |
| Cystatin C | CST3 | Kidney function; Glomerular filtration rate estimation (eGFR) | 1 ± – |
| Calprotectin | S100A8/S100A9 (complex) | Systemic inflammation marker; Leukocyte activation | 12.9 ± 0.1 |
| Beta-2-Microglobulin | B2M | Tumor marker (Myeloma, CLL, lymphoma); Kidney function assessment | 3.6 ± – |
| Complement Activity tests |
(CH50 test): C3; C1r (AH50 test): C3; CFD; CFHR1 |
Complement system evaluation; Immunodeficiency diagnosis |
(CH50) 4.6 ± 2.2 (AH50) 6 ± 5.6 |
| Complement C3 | C3 | Complement activation; Inflammatory/autoimmune disorders | 3.1 ± – |
| Complement C1r | C1r | Classical complement pathway activity | 6.1 ± – |
| Prostaglandin D-Synthase | PTGDS | Inflammation marker; Sleep regulation (research) | 2.7 ± – |
| Insulin-Like Growth Factor I | IGF1 | Growth disorders; Nutritional/endocrine assessmnet | 6.3 ± – |
| Creatine Kinase | CKM | Muscle injury diagnosis; Rhabdomyolysis; Myopathy | 13.8 ± – |
| Glyceraldehyde-3-phosphate dehydrogenase | GAPDH | Cellular damage; Hemolysis | 17.2 ± – |
| Heparin-PF4-IGG (HIT) | PF4 | Heparin-induced thrombocytopenia diagnosis | 18.7 ± — |
| Erythrocyte Transketolase Activity Test | TK | Vitamin B1 (Thiamine) deficiency diagnosis; Nutritional assessment | 18.9 ± — |
| Protein C | PROC | Thrombophilia evaluation; Coagulation disorders diagnosis | 5.7 ± – |
| HLA-AB | HLA-B | Transplant compatibility; Immunogenetic profiling | 7.1 ± – |
| Myoglobin | MB | Acute myocardial infarction (AMI); Rhabdomyolysis | 9.5 ± – |
| LDH | LDHA | Tissue injury; Hemolysis; Prognostic monitoring | 9.9 ± – |
| Total IgA | IGHA2 | Immunodeficiency diagnosis; Immune status monitoring | 19.5 ± – |
| Free Kappa Chains (Ig) | IGKV2D-29; IGKV2-28; IGKV2-29 | Plasma cell disorder diagnosis (Myeloma, MGUS); Therapeutic monitoring | 8.5 ± 8.1 |
| Free Lambda Chains (Ig) | IGLV3-25; IGLV3-19; IGLV2-11; IGLV3-1 | Plasma cell disorder diagnosis (Myeloma, MGUS); Therapeutic monitoring | 2.1 ± 1 |
| Free Kappa/Lambda Chains (Ig) Ratio | IGKV2D-29; IGKV2-28; IGKV2-29; IGLV3-25; IGLV3-19; IGLV2-11; IGLV3-1 | Plasma cell disorders diagnosis; Disease monitoring; Clonality analysis | 4.9 ± 5.9 |
|
CD56 Flow Cytometry (whole blood) |
NCAM1 | NK/T-cell malignancy diagnosis; Immunophenotyping | 22.1 ± – |
| Amylase | AMY2A | Acute pancreatitis diagnosis; Pancreatic function assessment | 19.4 ± – |
| Antithrombin | SERPINC1 | Thrombosis risk; Coagulation inhibitor deficiency | 2.2 ± – |
| Coagulation Factor XI | F11 | Hemophilia C; Bleeding disorder evaluation | 7.5 ± – |
| Coagulation Factor V | F5 | Factor V deficiency diagnosis; Thrombophilia evaluation | 6 ± – |
| Transferrin-Receptor Fragment | TFRC | Iron deficiency diagnosis; Iron metabolism assessment | 18.5 ± – |
| Coagulation Factor IX | F9 | Hemophilia B; Factor IX Deficiency; Vitamin K deficiency | 1.8 ± – |
The listed blood tests correspond to clinical routine assays according to the standardized regional clinical laboratory test preference list in Denmark (EPIC system, Region H, Denmark). Diurnally-regulated proteins linked to each test are indicated alongside descriptions of their diagnostic, prognostic, or monitoring significance in clinical practice. Note: Acrophase values are absolute 24-h clock times (0–24 h), not times relative to sampling start
aPTT, activated partial thromboplastin time; PT, prothrombin time; AMI, acute myocardial infarction; MGUS, monoclonal gammopathy of undetermined significance; eGFR, estimated glomerular filtration rate; HIT, heparin-induced thrombocytopenia; CLL, chronic lymphocytic leukemia; LDH, lactate dehydrogenase; Ig, immunoglobulin