A specific diagnostic metabolome signature in adult IgA vasculitis.

INTRODUCTION: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. OBJECTIVE: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. METHODS: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. RESULTS: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. CONCLUSION: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.

Time for optimism in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is among the most common motor neuron diseases in adults. Nevertheless, ALS remains fatal, despite decades of research and clinical trials, which has led to negative conclusions until recently in regard to four specific treatments. It is well known that we can learn from failures, and we consider that the time has come to present positive insight on this disease. METHODS: We did a literature search using PubMed and Scopus for articles published in English from 1 January 2016, to 30 June 2022 dealing with "amyotrophic lateral sclerosis", diagnosis, treatment, and biomarkers. RESULTS: A comprehensive review of the literature on diagnosis, monitoring, and treatment of this condition showed convincing evidence that we are now able to diagnose earlier as well as to better monitor and treat ALS. CONCLUSIONS: Although ALS is often difficult to diagnose and remains incurable, there are many indications that an optimistic view of ALS management in the coming years is now realistic.

Comparison between PFN1 and SOD1 mutations in amyotrophic lateral sclerosis.

BACKGROUND: The objective of this study was to characterize the prototypical phenotype of patients with amyotrophic lateral sclerosis (ALS) associated with PFN1 mutations in profilin 1 (PFN1) and to determine clinical indications to test for mutations in this gene. MATERIAL AND METHODS: The phenotype of three relatives carrying the M114V PFN1 mutation are detailed here and are compared with those of patients with ALS linked to PFN1 previously reported in the literature. RESULTS: In this pedigree and in the literature, the main clinical findings which best describe familial ALS linked to PFN1 might be the following characteristics: pedigrees over five cases, age of onset around 50 years, site of onset systematically lower limbs and the absence of cognitive impairment. CONCLUSION: First, the infrequent incidence of patients with ALS linked to PFN1 mutation supports the pursuit of a precise characterization of the phenotype linked to PFN1 mutations. Then, the numerous similarities between the phenotype amongst patients linked to SOD1 and PFN1 mutations and between histological features amongst both mice models prompts a review of the current ALS classifications, taking into consideration both phenotype and genotype.

Evaluation of arterial blood gas parameters as prognostic markers in amyotrophic lateral sclerosis.

BACKGROUND: Forced vital capacity (FVC) remains difficult to determine for some patients suffering from amyotrophic lateral sclerosis (ALS) due to the rapid progression of the disease. Arterial blood gas (ABG) parameters could represent a valuable alternative. The aim of this study was therefore to evaluate the correlation between ABG parameters and FVC, along with the prognostic ability of ABG parameters, in a large cohort of ALS patients. METHODS: ALS patients (n=302) with FVC and ABG parameters available at diagnosis were included. Correlations between ABG parameters and FVC were evaluated. Cox regression was then carried out to determine the association of each parameter (ABG and clinical data) with survival. Finally, receiver operating characteristic (ROC) curves were built to predict the survival of ALS. RESULTS: Bicarbonates (HCO3 - ), oxygen partial pressure (pO2 ), carbon dioxide partial pressure (pCO2 ), base excess (BE), oxygen saturation and oxyhemoglobin were significantly correlated with FVC both in patients with spinal or bulbar onset. Univariate Cox regression showed that HCO3 - and BE were associated with survival but only in spinal forms. ABG parameters predicted the survival of ALS with a similar performance to FVC, HCO3 - being the parameter with the highest area under the curve. CONCLUSIONS: Our results suggest that there is an interest in conducting a longitudinal evaluation throughout disease progression to confirm the equal performances of FVC and ABG. This study highlights the benefits of performing ABG analysis that could be used as an interesting alternative to FVC when spirometry cannot be performed.

Implication of Central Nervous System Barrier Impairment in Amyotrophic Lateral Sclerosis: Gender-Related Difference in Patients.

Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours (n = 307) were included in this monocentric, retrospective study. In total, 92 patients (30%) had elevated QAlb levels. This percentage was higher in males (43%) than in females (15%). Interestingly, QAlb was not associated with age of onset, age at sampling or diagnostic delay. However, we found an association with ALS functional rating scale-revised (ALSFRS-r) at diagnosis but this was significant only in males. The QAlb levels were not linked to the presence of a pathogenic mutation. Finally, we performed a multivariate survival analysis and found that QAlb was significantly associated with survival in male patients (HR = 2.3, 95% CI = 1.2-4.3, p = 0.009). A longitudinal evaluation of markers of barrier impairment, in combination with inflammatory biomarkers, could give insight into the involvement of CNS barrier impairment in the pathogenesis of the disease. The gender difference might guide the development of new drugs and help personalise the treatment of ALS.

Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3 Ligase NEDL1.

The ubiquitin pathway, one of the main actors regulating cell signaling processes and cellular protein homeostasis, is directly involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). We first analyzed, by a next-generation sequencing (NGS) strategy, a series of genes of the ubiquitin pathway in two cohorts of familial and sporadic ALS patients comprising 176 ALS patients. We identified several pathogenic variants in different genes of this ubiquitin pathway already described in ALS, such as FUS, CCNF and UBQLN2. Other variants of interest were discovered in new genes studied in this disease, in particular in the HECW1 gene. We have shown that the HECT E3 ligase called NEDL1, encoded by the HECW1 gene, is expressed in neurons, mainly in their somas. Its overexpression is associated with increased cell death in vitro and, very interestingly, with the cytoplasmic mislocalization of TDP-43, a major protein involved in ALS. These results give new support for the role of the ubiquitin pathway in ALS, and suggest further studies of the HECW1 gene and its protein NEDL1 in the pathophysiology of ALS.

Clinical and biochemical footprints of inherited metabolic diseases. IX. Metabolic ear disease.

Damages to the ear are very diverse and can depend on the type of inherited metabolic diseases (IMD). Indeed, IMDs can affect all parts of the auditory system, from the outer ear to the central auditory process. We have identified 219 IMDs associated with various types of ear involvement which we classified into five groups according to the lesion site of the auditory system: congenital external ear abnormalities, acquired external ear abnormalities, middle ear involvement, inner ear or retrocochlear involvement, and unspecified hearing loss. This represents the ninth issue in a series of educational summaries providing a comprehensive and updated list of metabolic differential diagnoses according to system involvement.

The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.

The ubiquitin pathway regulates the function of many proteins and controls cellular protein homeostasis. In recent years, it has attracted great interest in neurodevelopmental and neurodegenerative diseases. Here, we have presented the first review on the roles of the 9 proteins of the HECT E3 ligase NEDD4 subfamily in the development and function of neurons in the central nervous system (CNS). We discussed their regulation and their direct or indirect involvement in neurodevelopmental diseases, such as intellectual disability, and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease or Amyotrophic Lateral Sclerosis. Further studies on the roles of these proteins, their regulation and their targets in neurons will certainly contribute to a better understanding of neuronal function and dysfunction, and will also provide interesting information for the development of therapeutics targeting them.

Effect of familial clustering in the genetic screening of 235 French ALS families.

OBJECTIVES: To determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved. METHODS: We conducted a targeted next-generation sequencing analysis on 235 French familial ALS (FALS), unrelated probands to identify mutations in 30 genes linked to the disease. The genealogy, that is, number of cases and generations with ALS, gender, age, site of onset and the duration of the disease were analysed. RESULTS: Regarding the number of generations, 49 pedigrees had only one affected generation, 152 had two affected generations and 34 had at least three affected generations. Among the 149 pedigrees (63.4%) for which a deleterious variant was found, an abnormal G4C2 expansion in C9orf72 was found in 98 cases as well as SOD1, TARBP or FUS mutations in 30, 9 and 7 cases, respectively. Considering pedigrees from the number of generations, abnormal G4C2 expansion in C9orf72 was more frequent in pedigrees with pairs of affected ALS cases, which represented 65.2% of our cohort. SOD1 mutation involved all types of pedigrees. No TARDBP nor FUS mutation was present in monogenerational pedigrees. TARDBP mutation predominated in bigenerational pedigrees with at least three cases and FUS mutation in multigenerational pedigrees with more than seven cases, on average, and with an age of onset younger than 45 years. CONCLUSION: Our results suggest that familial clustering, phenotypes and genotypes are interconnected in FALS, and thus it might be possible to target the genetic screening from the familial architecture and the phenotype of ALS cases.

Quality consideration for the validation of urine TMA and TMAO measurement by nuclear magnetic resonance spectroscopy in Fish Odor Syndrome.

OBJECTIVES: Trimethylaminuria, also known as Fish Odor Syndrome (FOS), is a condition characterized by the presence of high concentrations of trimethylamine (TMA) in urine, sweat and expired air of affected patients. Diagnosis of this benign but unpleasant disease is mainly based on clinical presentation and assessment of TMA and its metabolite, TMAO (trimethylamine-N-oxide), concentrations in urine of patients. MATERIAL AND METHODS: We here described the validation of an analytical method for measurement of TMA and TMAO in urine using nuclear magnetic resonance (NMR) according to the specifications of the ISO 15189 norm. We used a fast validation protocol, based exactitude profile method, enabling to determine accuracy, intra and inter-day precision from a limited number of samples. RESULTS: The linearity was established from 2.5 to 100 mg/L for TMA measurement and from 10 to 1000 mg/L for TMAO measurement, with good analytical performances i.e. accuracy, intra and inter-day precision. We also report a case diagnose for FOS from this method. CONCLUSIONS: This method validation ensures the robustness of NMR in routine use for diagnosis of trimethylaminuria, as part of the reference center for inherited metabolic diseases at the Tours hospital.

Sensitivity of Capillary Electrophoresis to Detect Monoclonal Immunoglobulins: a Report of Two Cases and a Systematic Review.

BACKGROUND: The detection of monoclonal immunoglobulins (MIg) is a key element in the diagnosis of monoclonal gammopathies. METHODS: Here we report two cases of high concentration serum IgM-kappa MIgs (6.4 g/L and 6.8 g/L) not detected with capillary electrophoresis (CE). A systematic literature search was conducted to assess the sensitivity of CE to detect MIgs. RESULTS: The CE sensitivity to detect MIgs did not exceed 0.9 to 0.95 compared to immunofixation as standard. On the one hand, MIgs with blood concentrations below 1 g/L may be hidden by other serum proteins. On the other hand, some MIgs of high concentrations are not detected due to their insolubility in the electrophoresis buffer. CONCLUSIONS: Performing a second SPE with agarose gel electrophoresis method or modifying buffer properties may reveal some MIgs not detected by a first SPE alone.

Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation.

Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations.

Optimization of Sample Preparation for Metabolomics Exploration of Urine, Feces, Blood and Saliva in Humans Using Combined NMR and UHPLC-HRMS Platforms.

Currently, most clinical studies in metabolomics only consider a single type of sample such as urine, plasma, or feces and use a single analytical platform, either NMR or MS. Although some studies have already investigated metabolomics data from multiple fluids, the information is limited to a unique analytical platform. On the other hand, clinical studies investigating the human metabolome that combine multi-analytical platforms have focused on a single biofluid. Combining data from multiple sample types for one patient using a multimodal analytical approach (NMR and MS) should extend the metabolome coverage. Pre-analytical and analytical phases are time consuming. These steps need to be improved in order to move into clinical studies that deal with a large number of patient samples. Our study describes a standard operating procedure for biological specimens (urine, blood, saliva, and feces) using multiple platforms (1H-NMR, RP-UHPLC-MS, and HILIC-UHPLC-MS). Each sample type follows a unique sample preparation procedure for analysis on a multi-platform basis. Our method was evaluated for its robustness and was able to generate a representative metabolic map.

Assessment of the glomerular filtration rate (GFR) in kidney transplant recipients using Bayesian estimation of the iohexol clearance.

Background Plasma iohexol clearance (CLiohexol) is a reference technique for glomerular filtration rate (GFR) determination. In routine practice, CLiohexol is calculated using one of several formulas, which have never been evaluated in kidney transplant recipients. We aimed to model iohexol pharmacokinetics in this population, evaluate the predictive performance of three simplified formulas and evaluate whether a Bayesian algorithm improves CLiohexol estimation. Methods After administration of iohexol, six blood samples were drawn from 151 patients at various time points. The dataset was split into two groups, one to develop the population pharmacokinetic (POPPK) model (n = 103) and the other (n = 48) to estimate the predictive performances of the various GFR estimation methods. GFR reference values (GFRref) in the validation dataset were obtained by non-compartmental pharmacokinetic (PK) analysis. Predictive performances of each method were evaluated in terms of bias (ME), imprecision (root mean square error [RMSE]) and number of predictions out of the ±10% or 15% error interval around the GFRref. Results A two-compartment model best fitted the data. The Bayesian estimator with samples drawn at 30, 120 and 270 min allowed accurate prediction of GFRref (ME = 0.47%, RMSE = 3.42%), as did the Brøchner-Mortensen (BM) formula (ME = - 0.0425%, RMSE = 3.40%). With both methods, none of the CL estimates were outside the ±15% interval and only 2.4% were outside the ±10% for the BM formula (and none for the Bayesian estimator). In patients with GFR ≤30 mL/min/1.73 m2, the BM formula performed very well, while the Bayesian method could not be evaluated in depth due to too small a number of patients with adequate sampling times. Conclusions GFR can be estimated with acceptable accuracy in kidney transplant patients using the BM formula, but also using a Bayesian algorithm.

The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: a resolution in sight?

Transactive response DNA-binding protein-43 (TDP-43) is an RNA/DNA binding protein that forms phosphorylated and ubiquitinated aggregates in the cytoplasm of motor neurons in amyotrophic lateral sclerosis, which is a hallmark of this disease. Amyotrophic lateral sclerosis is a neurodegenerative condition affecting the upper and lower motor neurons. Even though the aggregative property of TDP-43 is considered a cornerstone of amyotrophic lateral sclerosis, there has been major controversy regarding the functional link between TDP-43 aggregates and cell death. In this review, we attempt to reconcile the current literature surrounding this debate by discussing the results and limitations of the published data relating TDP-43 aggregates to cytotoxicity, as well as therapeutic perspectives of TDP-43 aggregate clearance. We point out key data suggesting that the formation of TDP-43 aggregates and the capacity to self-template and propagate among cells as a 'prion-like' protein, another pathological property of TDP-43 aggregates, are a significant cause of motor neuronal death. We discuss the disparities among the various studies, particularly with respect to the type of models and the different forms of TDP-43 used to evaluate cellular toxicity. We also examine how these disparities can interfere with the interpretation of the results pertaining to a direct toxic effect of TDP-43 aggregates. Furthermore, we present perspectives for improving models in order to better uncover the toxic role of aggregated TDP-43. Finally, we review the recent studies on the enhancement of the cellular clearance mechanisms of autophagy, the ubiquitin proteasome system, and endocytosis in an attempt to counteract TDP-43 aggregation-induced toxicity. Altogether, the data available so far encourage us to suggest that the cytoplasmic aggregation of TDP-43 is key for the neurodegeneration observed in motor neurons in patients with amyotrophic lateral sclerosis. The corresponding findings provide novel avenues toward early therapeutic interventions and clinical outcomes for amyotrophic lateral sclerosis management.

Predicting the microbial cause of community-acquired pneumonia: can physicians or a data-driven method differentiate viral from bacterial pneumonia at patient presentation?

BACKGROUND: Community-acquired pneumonia (CAP) requires urgent and specific antimicrobial therapy. However, the causal pathogen is typically unknown at the point when anti-infective therapeutics must be initiated. Physicians synthesize information from diverse data streams to make appropriate decisions. Artificial intelligence (AI) excels at finding complex relationships in large volumes of data. We aimed to evaluate the abilities of experienced physicians and AI to answer this question at patient admission: is it a viral or a bacterial pneumonia? METHODS: We included patients hospitalized for CAP and recorded all data available in the first 3-h period of care (clinical, biological and radiological information). For this proof-of-concept investigation, we decided to study only CAP caused by a singular and identified pathogen. We built a machine learning model prediction using all collected data. Finally, an independent validation set of samples was used to test the pathogen prediction performance of: (i) a panel of three experts and (ii) the AI algorithm. Both were blinded regarding the final microbial diagnosis. Positive likelihood ratio (LR) values > 10 and negative LR values < 0.1 were considered clinically relevant. RESULTS: We included 153 patients with CAP (70.6% men; 62 [51-73] years old; mean SAPSII, 37 [27-47]), 37% had viral pneumonia, 24% had bacterial pneumonia, 20% had a co-infection and 19% had no identified respiratory pathogen. We performed the analysis on 93 patients as co-pathogen and no-pathogen cases were excluded. The discriminant abilities of the AI approach were low to moderate (LR+ = 2.12 for viral and 6.29 for bacterial pneumonia), and the discriminant abilities of the experts were very low to low (LR+ = 3.81 for viral and 1.89 for bacterial pneumonia). CONCLUSION: Neither experts nor an AI algorithm can predict the microbial etiology of CAP within the first hours of hospitalization when there is an urgent need to define the anti-infective therapeutic strategy.

Aß1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sensitive molecules may be of interest in clinical practice. For example, markers related to other neurodegenerative diseases such as Alzheimer's disease (AD) could be fully explored. Here, we compared baseline levels of amyloidß1-42 (Aß1-42), total Tau, and phosphorylated-Tau (phospho-Tau) protein in the cerebrospinal fluid (CSF) of ALS patients to controls and correlated it with clinical parameters of ALS progression collected over 12 months. We observed increased levels of Aß1-42 (controls: 992.9 ± 358.3 ng/L; ALS: 1277.0 ± 296.6 ng/L; p < 0.0001) and increased Aß1-42/phospho-Tau ratio and Innotest Amyloid Tau Index (IATI) (both p < 0.0001). IATI and the phospho-Tau/total Tau ratio correlated positively with ALSFRS-R and weight at baseline. Multivariate analysis revealed that baseline ALSFRS-R was associated with Aß1-42 and phospho-Tau/total Tau ratio (p = 0.0109 and p = 0.0013, respectively). Total Tau and phospho-Tau levels correlated negatively with ALSFRS-R variation at months 6 and 9, respectively (p = 0.02 and p = 0.04, respectively). Phospho-Tau/total Tau ratio correlated positively with ALSFRS-R variation at month 9 (p = 0.04). CSF levels of Aß1-42 could be used as a complementary tool to ALS diagnosis, and total Tau and phospho-Tau levels may help establishing the prognosis of ALS. Further studies merit exploring the pathophysiological mechanisms associated with these markers. Despite their lack of specificity, phospho-Tau/total Tau and Aß1-42 should be combined to other biological and clinical markers in order to improve ALS management.

Raman spectroscopic screening of high and low molecular weight fractions of human serum.

This study explores the suitability of Raman spectroscopy as a bioanalytical tool, when coupled with ultra-filtration and multivariate analysis, to detect imbalances in both high molecular weight (total protein content, γ globulins and albumin) and low molecular weight (urea and glucose) fractions of the same samples of human patient serum, in the native liquid form. Ultracentrifugation was employed to separate and concentrate the high and low molecular weight fractions of the serum. Initially, aqueous solutions of the respective molecular species, covering physiologically relevant concentration ranges, were analysed to optimise the measurement protocols. An adapted Extended Multiplicative Signal Correction (EMSC) algorithm was applied to raw spectra to remove water background signal and spectral interferents (ß-carotene). Using a validated partial least squares regression modelling method, R2 values, Root Mean Square Error of Cross Validation (RMSECV) and standard deviations were established for the quantification of γ globulin, total protein, albumin, urea and glucose content of the patient serum samples. The study demonstrates that Raman spectroscopy in the liquid form is a viable alternative and/or adjunct to current clinical practice for the parallel analysis of high and low molecular weight fractions, and simultaneous analysis of multiple analytes in the low molecular weight fraction, of human serum for diagnostic applications.

Analysis of bodily fluids using vibrational spectroscopy: a direct comparison of Raman scattering and infrared absorption techniques for the case of glucose in blood serum.

Analysis of biomarkers present in the blood stream can potentially deliver crucial information on patient health and indicate the presence of numerous pathologies. The potential of vibrational spectroscopic analysis of human serum for diagnostic purposes has been widely investigated and, in recent times, infrared absorption spectroscopy, coupled with ultra-filtration and multivariate analysis techniques, has attracted increasing attention, both clinical and commercial. However, such methods commonly employ a drying step, which may hinder the clinical work flow and thus hamper their clinical deployment. As an alternative, this study explores the use of Raman spectroscopy, similarly coupled with ultra-filtration and multivariate analysis techniques, to quantitatively monitor diagnostically relevant changes of glucose in liquid serum samples, and compares the results with similar analysis protocols using infrared spectroscopy of dried samples. The analysis protocols to detect the imbalances in glucose using Raman spectroscopy are first demonstrated for aqueous solutions and spiked serum samples. As in the case of infrared absorption studies, centrifugal filtration is utilised to deplete abundant analytes and to reveal the spectral features of Low Molecular Weight Fraction analytes in order to improve spectral sensitivity and detection limits. Improved Root Mean Square Error of Cross Validation (RMSECV) was observed for Raman prediction models, whereas slightly higher R2 values were reported for infrared absorption prediction models. Summarising, it is demonstrated that the Raman analysis protocol can yield accuracies which are comparable with those reported using infrared absorption based measurements of dried serum, without the need for additional drying steps.