C-reactive protein

Overview

C-reactive protein (CRP) is a pentameric acute-phase protein produced primarily by the liver in response to inflammatory signaling, especially interleukin-6. It is widely used in clinical medicine as a nonspecific biomarker of systemic inflammation, tissue injury, infection, and treatment response. Because CRP rises rapidly and can be measured reproducibly in blood plasma or serum, it is commonly incorporated into diagnostic algorithms, prognostic models, and longitudinal monitoring across many disease areas.

Biologically, CRP participates in innate immune responses by binding to phosphocholine-containing ligands on damaged cells and some microbial surfaces, thereby promoting complement activation and opsonization. In recent biomedical research, CRP is frequently studied alongside ferritin, leptin, interleukin-6, tumor necrosis factor alpha, alpha-1-acid glycoprotein, and cluster of differentiation-14 as part of broader inflammatory signatures. It is also used as a covariate or outcome marker in studies of checkpoint inhibitor therapy, antiretroviral therapy, type 2 diabetes, COVID-19, chronic renal insufficiency, and metabolic dysfunction–associated steatotic liver disease.

Focus of Latest Publications

Recent studies have continued to use CRP as a marker of systemic inflammation, prognostic risk, and treatment response across oncology, infectious disease, hematology, neurology, surgery, and metabolic research.

In metastatic disease treated with radiotherapy after immune checkpoint inhibitor exposure, CRP was evaluated as a prognostic factor in a large multicenter real-world cohort. A Cox proportional hazards model identified CRP ≥5 mg/L as an independent negative prognostic factor for survival, alongside BMI ≥25 kg/m². This supports the use of CRP as a clinically relevant inflammatory marker in checkpoint inhibitor-refractory settings, where host inflammatory status may influence outcomes after radiotherapy.

In hematology and critical care, CRP was examined as a baseline biomarker for predicting ICU admission after CAR T-cell therapy, although the study noted that baseline parameters including albumin, CRP, and NT-proBNP lacked consistent validation. In another hematologic context, CRP was assessed in exploratory multivariable analysis of iron-related markers in myeloproliferative neoplasms; it was not independently associated with zinc protoporphyrin, suggesting limited utility for that specific iron-deficiency refinement question.

CRP also appeared in perioperative and surgical studies as a marker of postoperative inflammatory response. In robotic versus laparoscopic Roux-en-Y gastric bypass, CRP was used together with leukocyte counts to evaluate postoperative inflammation and short-term outcomes such as pain and length of stay. In total laryngectomy care, CRP peaked on postoperative day 3, with a mean value of 114 mg/L, illustrating the expected postoperative acute-phase response. In canine leishmaniosis treated with meglumine antimoniate plus allopurinol, CRP concentrations decreased significantly from diagnosis to Day 29, indicating reduced systemic inflammation during therapy.

Several studies used CRP in infectious disease and sepsis-related contexts. In advanced HIV disease in Uganda, serum CRP was evaluated as a predictor of 30-day hospitalization or death among outpatients receiving the WHO-recommended package of care. In neonatal sepsis research, CRP served as a comparator biomarker against progranulin and procalcitonin for early detection before microbiological confirmation. In hemodialysis patients with end-stage renal disease and suspected acute cholecystitis, CRP showed moderate diagnostic performance, with an area under the curve of 0.733, slightly below the best-performing inflammatory index. In sepsis and acute pancreatitis, CRP was measured serially alongside IL-6, procalcitonin, CCL1, and CCL22 to help distinguish infectious from sterile systemic inflammation.

CRP was also integrated into broader inflammatory and immune profiling studies. In drug-resistant epilepsy, elevated CRP was part of a systemic immune dysregulation signature characterized by neutrophil activation and increased proinflammatory cytokines such as IL-6, CXCL8/IL-8, and TNF-α. In severe COVID-19, CRP was among the classical inflammatory markers associated with coagulopathy, together with ferritin, fibrinogen, erythrocyte sedimentation rate, lactate dehydrogenase, leptin, and IL-6. In Castleman’s disease, multicentric disease patients had higher CRP, consistent with the inflammatory phenotype of the disorder.

CRP has also been used in biomarker discovery and multivariable prediction models. In cerebral amyloid angiopathy, CRP contributed to a multi-protein plasma signature that, together with IL4, CCL11, NPY, PDLIM5, and demographic covariates, achieved an AUC of 0.90 in the discovery cohort for identifying neuropathologically confirmed disease. In head and neck squamous cell carcinoma, CRP was included among aging-related immune parameters evaluated for prognostic and immunotherapeutic implications. In colorectal cancer survival research, CRP was one of six inflammatory biomarkers assessed in relation to dietary processing exposure. In inflammatory bowel disease diagnostics, CRP remained a standard biomarker, although the study emphasized that traditional markers such as CRP and fecal calprotectin do not fully capture disease complexity or microbial dysregulation.

Outside human medicine, CRP was also used in veterinary and experimental research. In canine leishmaniosis, CRP tracked treatment response. In cell-based anti-inflammatory work, an Artemisia monosperma extract reduced CRP gene expression in LPS-stimulated BJ cells and RAW264.7 macrophage-like cells, supporting anti-inflammatory activity in vitro. In hemodialysis-related inflammation studies, CRP was analyzed together with ferritin and iron metabolism markers, reflecting its role in anemia of inflammation.

Methodologically, recent work has used CRP in correlation analyses, receiver operating characteristic analysis, explainable machine learning, decision curve analysis, and multivariable regression frameworks. It has also been measured in blood plasma and serum using immunoassays such as CRiBDL-ELISA and portable microbubble-linked immunosorbent platforms. Across these studies, CRP continues to function as a robust but nonspecific marker that is most informative when interpreted alongside disease-specific biomarkers and clinical context.

Key Publications

• NEWJun In-bedroom renewed air as anti-inflammatory adjuvant therapy in cancer survivors: protocol for the randomised, placebo-controlled BREATHS N-of-1 trial series. (BMJ open, 2026, PMID 42303407): "Fine particulate matter (PM2.5) air filtration lowers interleukin-6 and C reactive protein (CRP) levels in high-risk cardiopulmonary groups, though potential synergistic or confounding effects with routine medications-statins, cyclo-oxygenase-2 inhibitors, beta-blockers-remain poorly understood."
• Jun Impact of C reactive protein on effectiveness of interleukin-17 and tumour necrosis factor inhibitors in axial spondyloarthritis: a Danish nationwide observational study. (RMD open, 2026, PMID 42303383): "To study the impact of C reactive protein (CRP) level at treatment start on interleukin-17 inhibitor (IL-17i) and tumour necrosis factor inhibitor (TNFi) effectiveness, including treatment retention, in axial spondyloarthritis (axSpA)."
• May Associations between degree of food processing, inflammatory biomarkers and colorectal cancer survival: a prospective cohort study. (Food & function, 2026, PMID 42052690): "Six inflammatory biomarkers (C-reactive protein and five hematological indices) were evaluated."
• May Δ-β2M as a dynamic biomarker for predicting ICU admission after CAR T-cell therapy. (Annals of hematology, 2026, PMID 42192014): "Baseline parameters (albumin, CRP, NT-proBNP) lacked consistent validation."
• May Robotic versus laparoscopic Roux-en-Y gastric bypass: a propensity-matched comparison of the inflammatory response and MASLD trajectories. (Journal of robotic surgery, 2026, PMID 42185695): "We evaluated the postoperative inflammatory response using leukocyte counts and C-reactive protein (CRP), and assessed short-term clinical outcomes, including pain and length of stay (LOS)."
• May Leveraging large language models to audit perioperative total laryngectomy care: anesthetic, nutritional, and complication profiles in a real‑world cohort. (Otolaryngologia polska = The Polish otolaryngology, 2026, PMID 42178846): "CRP peaked on postoperative day 3 (mean 114 mg/L)."
• May Value of functional iron parameters in diagnostic re-assessment of MPN: refinement of iron-deficiency markers by zinc protoporphyrin (ZPP). (Annals of hematology, 2026, PMID 42176009): "In exploratory multivariable analysis, PV, overt MF, and phlebotomy were independently associated with higher ZPP, whereas CRP and time from diagnosis were not."
• May Diagnostic utility of systemic inflammatory markers for acute cholecystitis in hemodialysis patients with end-stage renal disease. (Medicine, 2026, PMID 42175491): "In receiver operating characteristic analysis comparing histopathologically confirmed acute cases with RT controls, PIV showed the highest diagnostic accuracy (area under the curve [AUC] = 0.771), followed by C-reactive protein (AUC = 0.733) and SIRI (AUC = 0.732)."
• May Systemic immune dysregulation and neutrophil activation define prognostic inflammatory signatures in drug-resistant epilepsy. (JCI insight, 2026, PMID 41979892): "...characterized by elevated neutrophil-to-lymphocyte ratio, C-reactive protein, proinflammatory cytokines (IL-6, CXCL8/IL-8, TNF-α), and activated neutrophils (CXCR4+CD62Llo)."
• May A plasma protein signature for cerebral amyloid angiopathy. (Acta neuropathologica, 2026, PMID 42162487): "We further compared multi-biomarker models and found that a combination of CRP, IL4, CCL11, NPY and PDLIM5, plus demographic covariates showed an area under the curve (AUC) of 0.90 (95% CI 0.86-0.94) to identify neuropathologically confirmed CAA in the discovery cohort."