Urinary soluble CD163 is useful as "liquid biopsy" marker in lupus nephritis at both diagnosis and follow-up to predict impending flares.

Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC>0.972; p < 10-4 with a 100 % specificity threshold fixed at 320 ng/mmol), and for monitoring renal activity allowing prediction of impending flares and remissions in follow-up (AUC = 0.789, p < 10-4). LN-A patients with an elevated spot proteinuria/creatinuria ratio (p = 8 × 10-6) and sCD163/creatinuria ratio (p = 10-3) were at risk for developing end-stage kidney disease but sCD163/creatinuria ratio cannot substitute kidney biopsy to discriminate LN-A from other glomerulonephritis. Among serological markers (n = 14), anti-dsDNA and anti-C1q antibodies (Abs) (AUC>0.750 versus non-LN patients, and AUC>0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p < 0.001). In conclusion, and as compared to classical serological markers, the urinary sCD163/creatinuria ratio provides an additional parameter for monitoring LN patients.

Unexpected discovery of CRP analytical interference: A case report.

OBJECTIVES: Immunoturbidimetric assays are sensitive techniques in clinical biology that may be subjected to matrix effects, hook effects or aspecific reactions. Among these, large quantities of immunoglobulins can distort the intensity of the detected signal. This study illustrates the deleterious effect of analytical interference on clinical patient management, and assesses the practical relevance of a recently proposed algorithm for interference investigation. METHODS: Determination of C-Reactive Protein (CRP) concentration by liquid immunoprecipitation on latex particles coated with mouse anti-CRP monoclonal antibodies, rabbit anti-CRP polyclonal antibodies, by solid phase immunochemistry or by enzymatic assay. RESULTS: During the follow-up of a 75-year-old patient suffering from multiple chronic diseases in the Internal Medicine Department of Toulouse University Hospital, a severe infection was suspected facing a CRP plasma value over 700 mg/L while he was in remission of an indolent marginal zone lymphoma. Because of the absence of clinical signs of infection, an interference in the liquid immunoprecipitation CRP assay was suspected. The hypothesis of an interference due to anti-mouse autoantibodies was ruled out because of normal results for other immunoassays using different types of antibodies. Moreover, no interference was observed using solid phase immunochemistry assay. Protein electrophoresis and immunofixation documented a relapse of lymphoma along with the presence of abnormal monoclonal immunoglobulins interfering with CRP measurement. CONCLUSION: The interpretation of common clinical biochemistry parameters such as CRP can be difficult owing to analytical interferences. Reviewing all the pharmaco-clinico-biological data and collaboration with clinicians is of critical importance for optimal patient management.

Assessment of the predictive value of plasma calprotectin in the evolution of SARS-Cov-2 primo-infection.

BACKGROUND: The COVID-19 epidemic still calls for anticipation aimed at preventing the overloading of critical care services. With this in mind, the predictive value of easily accessible biomarkers is to be assessed. OBJECTIVE: Secretion of calprotectin is stimulated during an inflammatory process, especially in the cytokine storm. We tried to determine whether early plasma concentration of calprotectin in patients with primary SARS-CoV-2 infection could predict an adverse outcome in cases of COVID-19. METHODS: We included 308 patients with a primary diagnosis of SARS-CoV-2 confirmed by PCR. Heparinized tube samples, collected within the first 24 h of hospitalization, were used for biomarker assays, in which plasma calprotectin was included. Data from the patients' medical records and severity groups established subsequent to diagnosis at the end of hospitalization were collected. RESULTS: Early plasma calprotectin concentration is significantly associated with progression to a severe form of COVID-19 in patients with primary infection (Relative Risk: 2.2 [1.6-2.7]). In multivariate analysis, however, it does not appear to provide additional information compared to other parameters (age, GFR, CRP…). CONCLUSION: Our study shows that while an early single blood test for calprotectin could help to predict the progression of a primary SARS-CoV-2 infection, it is not superior to the other parameters currently used in emergency medicine. However, it paves the way for future considerations, such as the interest of this biomarker for high-risk infected patients (immunocompromised individuals…). Finally, the usefulness of early serial measurements of plasma calprotectin to assess progression towards severity of COVID-19 requires further assessment.

Evaluation of two anti-SARS-CoV-2 antibody immunoassays for monitoring patients on pre-exposure prophylaxis.

Pre-exposure prophylaxis (PrEP) is crucial to prevent severe COVID-19 in immunocompromised patients. A reliable method is needed to quantify anti-SARS-CoV-2 antibody levels for personalized monitoring during PrEP. We measured the binding antibody concentrations of 63 immunocompromised patients receiving 300mg or 600mg tixagevimab/cilgavimab on PrEP day and twice during the following 3 months. All blood samples were tested using the Abbott anti-SARS-CoV-2 IgG II Quant assay, the Roche Elecsys anti-SARS-CoV-2 S assay, and live virus-based neutralization assays. The results of the two immunoassays were correlated on day 0, 1 month, and 3 months post-PrEP. Passing-Bablok regression demonstrated higher anti-S concentration values measured with the Roche immunoassay compared to those measured with the Abbott immunoassay. Antibody concentrations were higher after 600 mg tixagevimab/cilgavimab prophylaxis than after 300 mg. The neutralizing antibody titers obtained using the omicron BA.5 and BA.2.75 strains were low. Both automated immunoassays are suitable for monitoring immunocompromised patients on PrEP.

Unusual circumstance for craniopharyngioma discovery on meningoencephalitis: a pediatric case report.

BACKGROUND: Craniopharyngioma is a rare condition in children, but it is the most frequent tumor that occurs in the hypothalamic pituitary region. Chemical meningitis has been described as an uncommon postoperative complication, but no chemical meningitis due to a spontaneous rupture leading to craniopharyngioma diagnosis in children has been reported. CASE PRESENTATION: This is a case of a 13-year-old boy presenting with fever, vomiting and headache for two days. The CT scan revealed a suprasellar lesion, and lumbar puncture showed aseptic meningitis. The cerebral MRI suggested a craniopharyngioma and the cerebrospinal fluid cholesterol concentration was abnormally high. A thorough medical history indicated some visual disturbance, which improved at the onset of meningitis, and an inflection of the growth curve. The anatomopathological analysis of the tumor confirmed the diagnosis of craniopharyngioma. CONCLUSIONS: This case is the first to report the discovery of a craniopharyngioma with meningoencephalitis caused by the rupture of a craniopharyngioma cyst in a child. Diagnosis was facilitated by determining the cholesterol level in the cerebrospinal fluid, as well as fine anamnesis to identify visual and growth disturbances.

Current immunoassays and detection of antibodies elicited by Omicron SARS-CoV-2 infection.

The present study aimed to determine whether current commercial immunoassays are adequate for detecting anti-Omicron antibodies. We analyzed the anti-SARS-CoV-2 antibody response of 23 unvaccinated individuals 1-2 months after an Omicron infection. All blood samples were tested with a live virus neutralization assay using a clinical Omicron BA.1 strain and four commercial SARS-CoV-2 immunoassays. We assessed three anti-Spike immunoassays (SARS-CoV-2 IgG II Quant [Abbott S], Wantaï anti-SARS-CoV-2 antibody ELISA [Wantaï], Elecsys Anti-SARS-CoV-2 S assay [Roche]) and one anti-Nucleocapsid immunoassay (Abbott SARS-CoV-2 IgG assay [Abbott N]). Omicron neutralizing antibodies were detected in all samples with the live virus neutralization assay. The detection rate of the Abbott S, Wantai, Roche, and Abbott N immunoassays were 65.2%, 69.6%, 86.9%, and 91.3%, respectively. The sensitivities of Abbott S and Wantai immunoassays were significantly lower than that of the live virus neutralization assay (p = 0.004, p = 0.009; Fisher's exact test). Antibody concentrations obtained with anti-S immunoassays were correlated with Omicron neutralizing antibody concentrations. These data provide clinical evidence of the loss of performance of some commercial immunoassays to detect antibodies elicited by Omicron infections. It highlights the need to optimize these assays by adapting antigens to the circulating SARS-CoV-2 strains.