A challenge in diagnosing and monitoring radiographic axial spondyloarthritis (r-axSpA) is the absence of reliable biomarkers. This cross-sectional pilot study aimed to evaluate platelet- and neutrophil-derived substances as potential biomarkers in r-axSpA, given the involvement of these cells in disease pathology. Serum and plasma were collected from 13 male, HLA-B27-positive r-axSpA patients without disease-modifying anti-rheumatic drugs and 13 age- and sex-matched blood donor controls. Concentrations of platelet-derived soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) and neutrophil-derived human neutrophil lipocalin (HNL), myeloperoxidase (MPO), and galectin-3 were measured using ELISA. Associations between these markers and clinical parameters, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were assessed by Spearman’s rank correlation. Group differences were analysed using the Wilcoxon signed-rank test. Median concentrations of serum sCD40L (4.2 vs. 2.7 ng/mL; p = 0.001), plasma HNL (23.7 vs. 18.6 mg/L; p = 0.040), serum HNL (74.7 vs. 52.3 mg/L; p = 0.013), and plasma MPO (56.6 vs. 37.3 mg/L; p = 0.027) were significantly higher in r-axSpA patients compared with controls. Plasma HNL correlated positively with CRP and ESR, but not with other clinical parameters. In both patients and controls, serum concentrations of sCD40L, sP-selectin, HNL, and MPO were significantly higher than their plasma counterparts, highlighting differences related to sample processing. Serum sCD40L, serum and plasma HNL, and plasma MPO were elevated in r-axSpA patients compared with controls. These findings warrant validation in larger cohorts to clarify the role of sCD40L, HNL and MPO across a heterogeneous group of patients with early and established r-axSpA.

The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. In this study, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and body mass index, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8262 individuals and up to 5416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.

Abstract Background: Diffuse large-cell B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphomas (NHL) that accounts for approximately 25% of the patients. Earlier studies demonstrated the prognostic value of serum thymidine kinase 1 (STK1) activity determinations in different hematological malignancies. To date, the prognostic value of STK1 protein concentration in patients with DLBCL treated with R-CHOP has not been investigated. The purpose of this retrospective study was to determine the value of high TK levels on Overall survival among DLBCL patients treated with R-CHOP as first-line treatment. Materials and Methods: The study included 146 patients diagnosed with DLBCL between 2010 and 2016 from the Uppsala-Umeå Comprehensive Cancer Consortium (U-CAN). All patients included were treated using the standard chemotherapy regimen R-CHOP. Serum samples were collected at the time of diagnosis, during the treatment, 1 year after treatment, and after relapse. Non-infected and apparently healthy persons, matched to the DLBCL patients (57 males and 88 females), served as controls. The TK1 protein levels in all serum samples were determined by using AroCell TK 210 ELISA (AroCell AB, Sweden). The TK1 protein concentration was expressed as μg/L. Results: The TK1 concentrations in sera from DLBCL patients before treatment were significantly higher compared to the concentrations in healthy individuals, median 0.44 μg/L (IQ range 0.22 to 1.06 μg/L) vs. median 0.22 μg/L (IQ range 0.18 to 0.29 μg/L, P<0.00001). Serum TK1 was also significantly higher in patients with more advanced stages (P<0.00001), higher IPI (P<0.00001), and in patients with B-symptoms (P<0.0001). Patients with STK1 protein levels below the cut-off value (0.45 μg/L) had significantly better OS and DFS (P=0.04 and P=0.0006, respectively) compared to patients with STK1 concentration above the cut-off. In multivariate analyses, dichotomized S-TK1 measurements before treatment were found to be significant for the risk of relapse in combination with either aaIPI or IPI (p<0.01). Conclusions: These results confirmed that STK1 concentration correlates with risk factors such as tumor burden, Ann Arbor stage, and IPI. In conclusion, patients with high TK1 concentrations at the time of diagnosis have short overall survival and STK1 concentrations are apparently a prognostic indicator for survival in patients treated with modern chemo-immunotherapy. Citation Format: Kiran Jagarlamudi, Gustaf Hedström, Per Venge, Staffan Eriksson, Daniel Molin, Gunilla Enblad. The Prognostic value of serum TK1 protein determinations using AroCell TK210 ELISA in DLBCL patients treated with R CHOP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5210.

BACKGROUND:Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by discomfort with constipation and/or diarrhea with unclear pathophysiology. We aimed to determine the activities of colorectal eosinophils, neutrophils and epithelial cells by biomarkers in feces reflecting these activities. METHODS:Fecal samples were collected from 185 patients with IBS before and after 8 weeks of placebo or mesalazine treatment and from 40 healthy subjects. Calprotectin, eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL) (pab/765) or dimer, human phospholipase BII-precursor (HPLBII-P) and myeloperoxidase (MPO) were measured by ELISA. Symptom scores were evaluated by diaries. RESULTS:HPLBII-P, HNL (pab/765) and EDN, proteins secreted by intestinal epithelial cells, were elevated in IBS patients as compared to healthy subjects (p < 0.0001-p = 0.008). In contrast, the neutrophil proteins calprotectin, MPO and HNL dimer were unaltered. The eosinophilic protein ECP was lower in IBS (p = 0.001). HNL (pab/765) (p = 0.01) and EDN (p = 0.004) increased in IBS patients after mesalazine treatment. Colo-rectal mucosa showed strong staining of HPLBII-P and western blotting of fecal extracts showed the presence of mainly monomeric, epithelial-associated HNL. CONCLUSIONS:The absence of signs of involvement of neutrophils and eosinophils in IBS suggests that activity of local epithelial cells rather than inflammation may be a major determinant of the disease. The measurements of EDN, HNL (pab/765), and HPLBII-P may serve as potential fecal biomarkers in the study and monitoring of IBS.

BACKGROUND:Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM:To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS:We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS:All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS:This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.

Background: A serious consequence of respiratory infections with SARS-CoV-2 is Acute Kidney Injury (AKI). The aim of this study was to evaluate some novel biomarkers measured in plasma for their associations with the outcome of this infection as to AKI and mortality. Methods: Four different HNL (Human Neutrophil Lipocalin) assays were constructed using different antibody configurations, reflecting both neutrophil and epithelial cell activities. TK-1 (Thymidine kinase-1) was measured as a sign of cell destruction and proliferation. For comparison the plasma concentrations of NGAL (Neutrophil Gelatinase Associated Lipocalin), the cytokines IL-6, IL-8 and IFN-γ and of cystatin C, and procalcitonin were also measured. One hundred and three patients with severe respiratory failure admitted to the ICU were sampled for blood at admittance and at day three (n=67) after admittance. Results: Sixty-five percent of the patients developed AKI. The performance of the HNL assay 763/8F was most closely associated to outcome as to AKI and mortality with Area Under the Receiver Operating Characteristics Curve (AUC) of 0.87 and a sensitivity of 80% and a specificity of 88% in COVID-19 patients with and without severe AKI (p<0.0001). TK-1 was significantly related to the development of AKI (p=0.01) and the three cytokines were related to mortality (p=0.004-p<0.001). Conclusion: The HNL variant 763/8F and TK-1 are novel biomarkers that might become useful and novel tools in the management of COVID-19 patients, but likely also in other patients affected by AKI.

Introduction Sepsis is a growing problem worldwide and associated with high mortality and morbidity. The early and accurate diagnosis and effective supportive therapy are critical for combating mortality. The aim of the study was to compare the kinetics of four biomarkers in plasma in patients admitted to ICU including sepsis and during antibiotics treatment. Methods The biomarkers evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), HNL Total and PCT (Procalcitonin). Plasma was obtained at admission to ICU and during follow-up at days 2 and 3. Antibiotic treatment was started or reviewed on admission to ICU. The results were compared to SOFA and KDIGO-scores and to survival. 277 patients admitted to ICU were included of which 30% had sepsis. The other groups were categorized as miscellaneous, other medical and trauma. Results The plasma concentrations of all four biomarkers were highly elevated with the highest concentrations in sepsis patients. During the follow-up period HNL Dimer decreased already day 2 and further so day 3 (p<0.00001) in contrast to unchanged concentrations of the other three biomarkers. HNL Total showed the strongest relationships to the clinical scores (p<0.0001) and was by multiples regression analysis independently related to these scores. Conclusion Our data supports and confirms our earlier findings of HNL Dimer being a novel and potentially useful clinical tool in antibiotic stewardship in sepsis. HNL Total reflects epithelial cell activity in the body and is an interesting biomarker for the management of organ failure in such patients.

HNL (human Neutrophil Lipocalin) is a protein secreted from the activated neutrophil granulocytes but also from epithelial cells. HNL is measured by sensitive immunoassays in most bodily fluids and exists in several variants of which the monomer and the dimer variants are the most abundant. Depending on the antibody configuration of the immunoassays we may detect different molecular variants of HNL, and which may have different cellular origins. The dimeric form of HNL is entirely neutrophil specific and other assays may preferentially detect HNL originating from epithelial cells such as the tubular cells of the kidney. In this brief review we have focused on the utility of HNL as a biomarker for antibiotics stewardship in patients with sepsis and show that the dimeric form of HNL is reduced within 24 hours as the response to successful antibiotic treatment in sepsis in contrast to the reduction of blood levels of procalcitonin and heparin-binding protein which takes 3-4 days. Another variant of HNL showed to be the most powerful predictor of outcome of these patients. We conclude that the measurements of these HNL variants should be considered for implementation in intensive care units and other settings with seriously ill infected patients.

Background: A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-CoV-2 infection was increased as a sign of glomerular dysfunction. The aim of this report was to investigate the relation of the urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations, i.e., the ULSAM and PIVUS cohorts. Methods: HPLBII-P was measured by an ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in the urine of a community-based cohort of 75-year-old men, n = 387, and women, n = 401 (PIVUS). KIM-1, NGAL, and albumin were measured in urine and cathepsin S and cystatin C in serum. Results: HPLBII-P was significantly raised among males with diabetes in the ULSAM (p < 0.0001) and PIVUS cohorts (p ≤ 0.02), but not in the female cohort of PIVUS. In the female subpopulation of insulin-treated diabetes, HPLBII-P was raised (p = 0.02) as compared to women treated with oral antidiabetics only. In the ULSAM cohort, HPLBII-P was correlated to NGAL, KIM-1, and albumin in urine both in non-DM (all three biomarkers; p < 0.0001) and in DM (NGAL; p = 0.002, KIM-1; p = 0.02 and albumin; p = 0.01). Plasma glucose and HbA1c in blood showed correlations to U-HPLBII-P (r = 0.58, p < 0.001 and r = 0.42, p = 0.004, respectively). U-HPLBII-P and cathepsin S were correlated in the ULSAM group (r = 0.50, p < 0.001). No correlations were observed between U-HPLBII-P and serum creatinine or cystatin C. Conclusions: The urine measurement of HPLBII-P has the potential to become a novel and useful biomarker in the monitoring of glomerular activity in diabetes mellitus.

Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.

Abstract Sepsis is a growing problem worldwide and associated with high mortality and morbidity. The early and accurate diagnosis and effective supportive therapy are critical for combating mortality. The aim of the study was to compare the kinetics of four biomarkers in plasma in patients admitted to ICU including sepsis and during antibiotics treatment. Methods The biomarkers evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), HNL Total and PCT (Procalcitonin). Plasma was obtained at admission to ICU and during follow-up at days 2 and 3. Antibiotic treatment was started or reviewed on admission to ICU. The results were compared to SOFA and KDIGO-scores and to survival. 277 patients admitted to ICU were included of which 30% had sepsis. The other groups were categorized as miscellaneous, other medical and trauma. Results The plasma concentrations of all four biomarkers were highly elevated with the highest concentrations in sepsis patients. During the follow-up period HNL Dimer decreased already day 2 and further so day 3 (p < 0.00001) in contrast to unchanged concentrations of the other three biomarkers. HNL Total showed the strongest relationships to the clinical scores (p < 0.0001) and was by multiples regression analysis independently related to these scores. Conclusion The neutrophil specific biomarker HNL Dimer seems to be a superior means to monitor the response to antibiotic treatment in ICU patients and confirms earlier findings of a rapid decline after adequate antibiotic treatment in sepsis. HNL Total reflects epithelial cell activity in the body and is an interesting biomarker for the management of organ failure in such patients.

INTRODUCTION:Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. METHODS:We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. RESULTS:In patients achieving clinical remission (n = 27), a decrease in levels of FC ( P = 0.005), MPO ( P < 0.001), HNL ( P < 0.001), and EDN ( P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO ( P = 0.01) and HNL ( P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL ( P = 0.01) and EDN ( P < 0.001) at baseline, compared with patients without corticosteroids. DISCUSSION:Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.

Thymidine Kinase 1 (TK1) plays an important role in DNA precursor synthesis and serum TK1 activity has been used as a biomarker for prognosis and therapy monitoring of different malignancies. AroCell has developed a dual monoclonal antibody ELISA for determination of TK1 protein in clinical samples. The purpose of the study is to validate the ELISA analytically in relation to the gold standard, [3H]-deoxythymidine (dThd) phosphorylation assay for TK1 activity using sera from patients with different malignancies. The colorimetric TK 210 ELISA was validated analytically by assessment of precision, linearity, interfering substances, and stability. For the clinical validation, serum samples from patients with hematological malignancies (n = 100), breast cancer (n = 56), prostate cancer (n = 70) and blood donors (n = 159) were analyzed using TK 210 ELISA and TK1 activity by [3H]-deoxythymidine (dThd) phosphorylation assay. The sandwich TK 210 ELISA was highly specific for TK1 protein having a detection limit of 0.12 ng/mL, with a functional sensitivity of 0.25 ng/mL. Within-run CVs ranged from 5.5% to 10% and between-run CVs ranged from 5% to 15%. The ratio of observed to expected dilutional parallelism of 5 serum samples was in the range of 80–120%. Samples exhibited stability through four freeze/thaw cycles and 5 days at 4°C. Further, the ROC curve analysis showed that TK 210 ELISA and [3H]-dThd phosphorylation assay had similar sensitivity (62% vs 59%) in hematological malignancies. However, in the case of breast and prostate cancer sera, TK 210 ELISA had higher sensitivity (59% and 44%) compared to [3H]-dThd phosphorylation assay (47% and 25%) at a specificity of 98%. These data demonstrate that the dual monoclonal antibody based AroCell TK 210 ELISA is a robust, accurate and precise tool for measuring TK1 protein in different malignancies that can improve the clinical applications of TK1 as a biomarker in cancer management.

Sepsis is a major burden to society and our health care systems. Early detection and treatment are keys to the improvement of the outcome of patients with sepsis with lower morbidity and mortality. We show in this review the potential usefulness, and superiority to current biomarkers, of plasma measurements of HNL Dimer in the monitoring of antibiotics in patients with sepsis. Future studies should be initiated to confirm this important aspect of sepsis management.

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Counting numbers of blood neutrophils is one of the most common laboratory tests in modern clinical medicine. In this report, we have tested the idea that immunoassay of major constituents of mature neutrophils might serve as proxy of cell counting and allow the development of rapid and simple point-of-care tests. The procedure may also allow for the estimate of the state of maturity of the circulating blood cells. Immunoassays for myeloperoxidase (MPO) and lactoferrin (LF) were used to measure the respective protein in whole blood extracts of 275 unselected hospitalized patient and in 51 healthy controls and leukemia patients of which eight were followed before, during and after remission treatment. MPO was correlated to neutrophil counts in the unselected hospitalized population (r = 0.95, p <.0001). Huge variations were seen in whole blood extracts of patients with AML with very high MPO/LF ratios in half of the AML patients and in all three patients with APL. In extracts from patients with ALL no difference was found in the ratio as compared to healthy persons. The monitoring of AML patients during remission treatment showed intriguing patterns one of which suggested the possibility to monitor the myelopoietic activity in the bone marrow during the recovery phase. We show a novel and easy technology to count mature neutrophils in blood and also to monitor myeloid cell maturity in the blood as well as myelopoietic activity in the bone marrow. The technology lends itself to the development of a rapid and simple point-of-care test.

Diagnosing persons infected by COVID-19 is key to the control of the pandemic. It has, however, become increasingly important to identify those who have had the infection by measurement of circulating antibodies against Sars-COV-2 of the IgM and IgG type. In this report we show the development of a rapid and sensitive point-of-care assay for the measurement of IgG antibodies against the two spike proteins, S1 and S2, of the Sars-COV-2 virus.MethodThe AgPlus electrochemical technology was applied and the S1 and S2 proteins were biotinylated and immobilized onto streptavidin coated magnetic particles as the capture component of the assay. The IgG antibodies bound to the particles were detected by anti-human IgG and the signal expressed as nC (nano Coulomb). Assay time was <10 min.ResultsPlasma (n=211) from 117 SARS-Cov-2 PCR positive patients and from 78 persons with samples taken before the COVID-19 pandemic were analysed. The sensitivity and specificity of the assay were 91.9% and 100%, respectively. The assay was highly correlated to a predicate and FDA-approved IgG antibody ELISA (r=0.81). The IgG response was significantly lower in patients who died during their ICU stay.ConclusionsA poor IgG response after a COVID-19 infection is a serious risk factor as to death. A sensitive, rapid and accurate IgG antibody POC assay should be useful in the daily management and evaluation of COVID-19 infected patients.

Background Thymidine kinase 1 (TK1) is an intracellular protein associated with DNA synthesis, expressed during the G1 phase and remained elevated through the M phase, with a potential as a biomarker for cell proliferation. In this study, we explore the possible use of TK1 in Hodgkin lymphoma (HL). Methods Serum concentrations of TK1 (S-TK1) were measured in 46 newly diagnosed HL patients using prospectively collected biobanked serum samples. The samples were analyzed using a novel antibody-based TK1 immunosorbent assay (ELISA). Results The concentrations of S-TK1 were elevated in HL patients compared with healthy controls (median 0.32 μg/L vs. 0.24 μg/L, P = 0.003). A further increase in S-TK1 was observed during the treatment. The S-TK1 concentrations were higher in patients with advanced stage disease, low B-Hb, elevated P-LD and in those with B-symptoms. A high ESR correlated with low S-TK1. Conclusions The study results suggest that S-TK1, measured using a novel antibody-based assay, has the potential to be a biomarker in HL. However, while S-TK1 levels are elevated at baseline compared with healthy controls, a limited number of patients and comparatively short follow-up time render reliable conclusions difficult.

Background The inflammatory process in juvenile idiopathic arthritis (JIA) involves both the innate and the adaptive immune system. The turnover and activity of neutrophil granulocytes may be reflected by proteins secreted from primary or secondary granules and from the cytoplasm of sequestered cells. Our primary aim was to compare the levels of the secondary neutrophil granule protein human neutrophil lipocalin (HNL), in JIA patients and controls, and to explore a possible priming of neutrophils through parallel analyses in plasma and serum. A secondary aim was to relate the levels of HNL to two other well-studied leukocyte proteins, S100A8/A9 and myeloperoxidase (MPO), as well as to clinical aspects of JIA. Methods The concentrations of the three biomarkers in serum, two of them also in plasma, were measured using enzyme-linked immunosorbent assay in 37 children with JIA without medical treatment, in high disease activity based on juvenile arthritis disease activity score 27 (JADAS27), 32 children on medical treatment, mainly in lower disease activity, and 16 healthy children. We assessed for differences between two groups using the Mann-Whitney U test, and used the Kruskal-Wallis test for multiple group comparisons. Spearman rank correlation, linear and multiple regression analyses were used for evaluation of associations between biomarker concentrations and clinical scores. Results The concentrations of HNL and MPO in serum were significantly increased in children with JIA ( p < 0.001, p = 0.002) compared with healthy children, but we found no difference in the plasma levels of HNL and MPO between children with JIA and controls. The serum concentrations of MPO and HNL were unaffected by medical treatment, but S100A8/A9 was reduced by medical treatment and correlated with JADAS27 in both univariate (r = 0.58, p < 0.001) and multivariate (r = 0.59, p < 0.001) analyses. Conclusions Neutrophil granulocytes in children with JIA are primed to release primary and secondary granule proteins, without relation to medical treatment, whereas signs of increased turnover and sequestration of neutrophil granulocytes are reduced by treatment. Levels of neutrophil-originating proteins in serum most likely reflect underlying disease activities of JIA.

Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality (p < 0.001–0.046). B-HNL performed similarly with the exception of mild AKI and mortality (p < 0.001–0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 µg/L and 190 µg/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure.