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Background: Upon infection activated plasma cells produce large quantities of antibodies which can lead to the emergence of a monoclonal component (MC), detectable by serum protein electrophoresis (SPEP). This study aims to investigate any correlation between SARS‐CoV‐2 infection and MC development and, if identified, whether it persists during follow‐up. Methods: SPEPs of 786 patients admitted to hospitals between March 01 2020 and March 31 2022 were evaluated. Positive (SARS‐CoV‐2+) and negative (SARS‐CoV‐2−) patients to nasopharyngeal swab for SARS‐CoV‐2 by RT‐PCR were included. The persistence/new occurrence of MC was investigated for all patients during follow‐up. Patient groups were compared by chi‐square analysis. Results: MC was identified in 12% of all patients admitted to hospital, of which 28.7% were SARS‐CoV‐2+. The most common immunoglobulin isotype in both groups was IgG‐k. There was no correlation between MC development and SARS‐CoV‐2 infection (p = 0.173). Furthermore, the risk of MC persistence in SARS‐CoV‐2‐negative patients was revealed to be higher than in the SARS‐CoV‐2+ at follow‐up (HR = 0.591, p = 0.05). Conclusions: Our study suggests that the detection of MC during SARS‐CoV‐2 infection is most likely due to the hyperstimulation of the humoral immune system, as also occurs in other viral infections. [ABSTRACT FROM AUTHOR]

Introduction: monoclonal antibodies therapeutic (t-mAbs) are used in the treatment of multiple myeloma (MM). They are composed of IgG-k and may interfere with the patient's endogenous IgG-k monoclonal component (MC). The Hydrashift test (Sebia, Lisses, FR), the daratumumab immunofixation reflex test (DIRA test), is able to eliminate interference by t-mAbs. This work aims to determine how many DIRA tests were performed in the laboratory of the Department of Laboratory Medicine of Modena (Italy) and how the DIRA test has been used in our daily practice and its impact on the clinical management of the patient as well. Methods: the DIRA test was applied by the laboratory on patients selected on the basis of: their clinical history, of monoclonal components, comparison with previous electrophoresis, the characteristic pattern of the gamma zone, and evidence of an additional peak in the gamma zone. The data were extracted from the laboratory information system. Results: from August 2021 to December 2022 we performed the DIRA test on 240 samples for a total of 160 patients. 198 (82.5%) samples came from onco-haematological wards or day hospitals, the remaining 17.5% included samples from external sampling centers or non-onco-haematological. In 88 (55%) patients the DIRA test was positive. Conclusions: the use of the DIRA test allowed a correct diagnosis in 55% of the patients undergoing electrophoretic examination. DIRA is an inexpensive test, easily performed in any laboratory; however, an effective use of the test requires a close collaboration between haematologists and the laboratory. [ABSTRACT FROM AUTHOR]

The protein concentration in urine is a valuable parameter in assessing kidney function. Usually, blood proteins do not pass through the renal filter in healthy subjects; proteinuria, which can sometimes be detected as a simple, occasional laboratory finding, is a relatively common condition of which those affected are unaware. Epidemiologically, it is a condition that involves almost 10% of the population worldwide. The mechanisms underlying the release of proteins by the kidneys are different: a newly detected proteinuria may precede the onset of renal disease or systemic diseases, and the physician must appropriately evaluate it. This paper provides a hint of epidemiology, some notes of pathophysiology, an overview of the types of proteinuria, a rundown on laboratory techniques and a brief, certainly not exhaustive, review of some non-oncological pathologies associated with proteinuria. The aim is to show the extent to which proteinuria can play a decisive role in the patient's overall assessment. The urine protein test, a basic, non-invasive test, easy to perform by any laboratory, even the most poorly equipped, is a fundamental indicator of a subject's health status in combination with other markers. Thus, it confirms once again the crucial role of the laboratory in providing the physician with necessary diagnostic and prognostic data that is easy to perform, inexpensive and yet of great benefit for the patient management. [ABSTRACT FROM AUTHOR]

Cryoproteinaemia is characterised by the presence of detectable proteins in both serum and plasma that precipitate at 4°C and dissolve at 37°C. Cryoglobulins are constituted by immunoglobulins and are detectable in both serum and plasma, whereas cryofibrinogen is detectable only in plasma. The importance of studying cryoproteinemia was the main theme of the meeting held in Modena in March 2023, entitled: Cryoglobulinemia. Laboratory and clinic, a fruitful collaboration for the correct management of a rare pathology - 4th edition, organised by the Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC) and the Italian Association for the fight against Cryoglobulinaemia (ALCRI). The aim of this conference is to promote a dialogue between clinicians and laboratory professionals, highlighting the information that the clinician expects from the laboratory and the critical points that the laboratory faces when performing a test that is still predominantly performed manually. During the meeting, data from three laboratories were presented and compared, and a group of clinicians who deal with cryoproteinemia in different medical fields -- rheumatologists, nephrologists, haematologists, and neurologists -- contributed their experience in treating patients with cryoproteinemia. The collaboration between laboratory and clinic and the respective scientific societies (SIBioC and ALCRI) have made possible to draw a common line to guide both entities in their daily activity. The road seems long and complex, but a common system is emerging from this interaction, the fruits from which patient will benefit. [ABSTRACT FROM AUTHOR]

Introduction: cryoproteinemia is associated with a broad spectrum of clinical symptoms and significant variability among patients; in this context, laboratory diagnostics play a crucial role in diagnosis and treatment. However, diagnosing cryoglobulinemia is difficult from a clinical point of view and in the laboratory. SIBioC (Italian Society of Clinical Biochemistry and Molecular Biology) has proposed a survey to the Italian laboratories to assess the adopted methods. Methods: the survey consisted of 40 questions: 8 concerning general items, 9 on the pre-analytical phase, 14 on the analytical phase, 4 on the post-analytical phase, and 5 on the cryofibrinogen. Results: sixty-six laboratories responded to the survey, mainly from Northern Italy. The results show non-homogeneous situation. Preanalytical phase: some laboratories are not equipped with adequate devices for transporting the sample maintaining a temperature-controlled chain. Analytical phase: not all laboratories apply the same procedures to separate the serum, to wash the cryo-precipitate and to measure the cryocrit. Postanalytical phase: almost all laboratories apply the Brouet classification. 11% of laboratories perform cryofibrinogen testing, 20% participate in an external quality assessment, and 62% of participants feel the need for an adequate scientific information and training. Conclusions: the survey shows that the procedures for cryoprotein testing vary widely among laboratories. The need of recommendations emerges strongly; these could start from the existing literature in the field, the already available procedures, trying make a synthesis where the processes are diversified. It is also crucial to participate to External Quality Assessment and to spread the culture of continuous dialogue with clinicians. [ABSTRACT FROM AUTHOR]

Cryofibrinogen (CF) is an abnormal protein in plasma that precipitates at 4 °C and dissolves at 37 °C. Whilst serum cryoglobulins (CGs) analysis is common practice, CF investigation is rarely performed. This study aims to describe the testing methodology developed at our laboratory, potential pitfalls for all analytical phases, the distribution among hospital wards and clinical conditions underlying test requests and clinical conditions in which to order CF analysis is useful. Retrospective analysis of laboratory samples received between January 2019 and June 2021 with CF testing requests. A complete protocol for CF pre-analytical, analytical and post-analytical phases are supplied. Most test requests were received from the rheumatology department for systemic sclerosis or liver transplant screening. Among the 103 in-patients included, CF+ was confirmed in 68 patients (66%). Of observed CF+ patients (n=68) most cases were CGs− (n=44, 67%). Isolated CF was found in 43% of the cases. Among CF− patients (n=35; 34%) only 2 patients had positive CGs (CGs+). Among rheumatology patients (n=66), isolated CF+ was observed in 45% (n=30/66), whilst among patients with systemic sclerosis with CF+ (n=19), isolated CF+ was detected in 79% (n=15/19). Described analytical procedures may be used for the creation of harmonized recommendations and indications for CF analysis. Isolated CF positivity among hospitalized patients, predominantly rheumatology and systemic sclerosis patients, appears higher than rates previously reported in literature. We propose CF test recommendations should be included in investigation protocols for diseases where cryofibrinogenemia may occur. [ABSTRACT FROM AUTHOR]

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays. [ABSTRACT FROM AUTHOR]

The article offers information on frequency and results of cryoglobulin retesting in patients. Topics include the cryoglobulinemia being a rare pathologic condition that being difficult to diagnose both clinically and in the laboratory, and beginning with the necessity of maintaining the sample at 37°C during the preanalytical phase until centrifugation in the laboratory.

The Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC) has long promoted harmonizing activities, focusing on the laboratory reports to guarantee accuracy and comparability of the results. There is a wealth of guidelines on the clinical usefulness and diagnostic accuracy of serum protein electrophoresis (SPE), but only few provide specific recommendations for reporting and commenting the results. According to surveys and international multi-center studies, there is considerable variability between SPE reports among laboratories, which negatively impacts the management of patients with monoclonal gammopaties (MGs). This document issued by the SIBioC Study Group on Proteins, provides guidance on how to standardize and harmonize laboratory SPE reports, formulated on the basis on the available reference literature as well as on expert consensus. Each SPE report should be accompanied by a descriptive comment, mainly related to the management of samples with monoclonal components (detection, quantification and immunotyping). Examples of comments are provided. Special attention should be dedicated to samples showing a possible interference by therapeutic monoclonal antibodies (tmAb) currently used for the treatment of Multiple Myeloma (MM). Failure to detect interference due to tmAb can lead to further unnecessary diagnostic procedures or incorrect interpretations of the efficacy of treatment, such as the failure to detect a complete response to treatment in MM patients. Close collaboration between laboratory professionals and clinicians is therefore of paramount importance to provide correct information that will be useful in every step of the management of MGs patients. [ABSTRACT FROM AUTHOR]

Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies. [ABSTRACT FROM AUTHOR]

Inflammation and inflammasomes have been proposed as important regulators of the host–microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) is a hematologic cancer originating from underlying precursor disorders, called Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). In order to predict the risk of progression from MGUS/SMM to MM, well-known prognostic factors are currently used in the clinical management, but the contribute of myeloma-specific T-cell immunity still remains to be addressed in this context. In this work, we shed light on the relevant dynamics of MM-specific T cells in a long-term cohort of MGUS/SMM patients, in particular describing a new prognostic tool, namely Multi-antigenic Myeloma-specific (MaMs) T-cell assay, which may be useful to assess the presence of a protective MM-specific immunity, possibly representing a novel immunologic marker of effective disease control. Our work can be considered a promising proof-of-concept for future larger studies, aiming to further explore the prognostic impact of MaMs-based tests in the management of patients with monoclonal gammopathies. Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information. [ABSTRACT FROM AUTHOR]