Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency.

Genetic defects in the ability to deliver effective perforin have been reported in patients with hemophagocytic lymphohistiocytosis. We tested the hypothesis that a primary perforin deficiency might also be causal in severe SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to intensive care units or non-intensive care units and age- and sex-matched healthy controls. Compared with healthy controls, the percentage of perforin-expressing CD3-CD56+ NK cells quantified by flow cytometry was low in COVID-19 patients (69.9 ± 17.7 versus 78.6 ± 14.6%, p = 0.026). There was no correlation between the proportions of perforin-positive NK cells and T8 lymphocytes. Moreover, the frequency of NK cells producing perforin was neither linked to disease severity nor predictive of death. Although IL-6 is known to downregulate perforin production in NK cells, we did not find any link between perforin expression and IL-6 plasma level. However, we unveiled a negative correlation between the degranulation marker CD107a and perforin expression in NK cells (r = -0.488, p = 10-4). PRF1 gene expression and the frequency of NK cells harboring perforin were normal in patients 1 y after acute SARS-CoV-2 infection. A primary perforin defect does not seem to be a driver of COVID-19 because NK perforin expression is 1) linked neither to T8 perforin expression nor to disease severity, 2) inversely correlated with NK degranulation, and 3) normalized at distance from acute infection. Thus, the cause of low frequency of perforin-positive NK cells appears, rather, to be consumption.

An immuno-DOT diagnostic assay for autoimmune nodopathy.

OBJECTIVES: Autoimmune nodopathy (AN) is a life-threatening peripheral neuropathy mediated by four autoantibodies targeting axoglial cell adhesion molecules at the nodes of Ranvier: Neurofascin-155 (Nfasc155), PanNeurofascin (PanNfasc), Contactin-1 (CNTN1), and Contactin-associated protein 1 (CASPR1). Antibody detection is a strong biomarker for AN diagnosis and treatment monitoring. The aim of this study was to develop an immuno-dot assay (immuno-DOT) compatible with routine implementation in medical laboratories. METHODS: This new approach was compared to standard techniques: indirect immunofluorescence assay, cell-based assay, and ELISA. Sensitivities (Se) and specificities (Sp) were calculated on a cohort composed of 58 patients diagnosed with AN, 50 seronegative patients with chronic inflammatory demyelinating polyradiculoneuropathy, 20 healthy controls, 30 patients with Guillain-Barré syndrome, 20 with monoclonal gammopathy and 20 with Charcot-Marie-Tooth disease. The patients were diagnosed with AN based on compatible electro-clinical arguments and at least two positive standard techniques. RESULTS: Immuno-DOT sensitivities and specificities were Se=91 %, Sp=97 % for anti-Nfasc155; Se=80 %, Sp=94 % for anti-PanNfasc; Se=93 %, Sp=98 % for anti-CNTN1; and Se=87 %, Sp=94 % for anti-CASPR1. Immuno-DOT allowed the diagnosis within 3 h and the accurate follow-up of the immune reactivity and isotype, and dot intensity correlated with antibody titers following treatments. A longitudinal study indicated that immuno-DOT yielded reliable results even after six months of storage at -20 °C. CONCLUSIONS: The diagnostic performance of immuno-DOT was satisfactory and compatible with routine implementation in medical laboratories.

Immune-mediated diseases involving central and peripheral nervous systems.

BACKGROUND AND PURPOSE: In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS). METHODS: To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria. RESULTS: Thirty patients (20 males) were included and followed during a median of 79.5 months (interquartile range [IQR] = 43-145). The median age at onset was 51.5 years (IQR = 39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n = 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n = 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n = 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n = 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n = 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n = 1), and systemic vasculitis (multineuropathy + CNS vasculitis/pachymeningitis, n = 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy + CNS demyelinating lesions, n = 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n = 4). CONCLUSIONS: We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers.

Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19.

BACKGROUND: Lymphopenia is predictive of survival in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: The aim of this study was to understand the cause of the lymphocyte count drop in severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Monocytic production of reactive oxygen species (ROSs) and T-cell apoptosis were measured by flow cytometry, DNA damage in PBMCs was measured by immunofluorescence, and angiotensin II (AngII) was measured by ELISA in patients infected with SARS-CoV-2 at admission to an intensive care unit (ICU) (n = 29) or not admitted to an ICU (n = 29) and in age- and sex-matched healthy controls. RESULTS: We showed that the monocytes of certain patients with COVID-19 spontaneously released ROSs able to induce DNA damage and apoptosis in neighboring cells. Of note, high ROS production was predictive of death in ICU patients. Accordingly, in most patients, we observed the presence of DNA damage in up to 50% of their PBMCs and T-cell apoptosis. Moreover, the intensity of this DNA damage was linked to lymphopenia. SARS-CoV-2 is known to induce the internalization of its receptor, angiotensin-converting enzyme 2, which is a protease capable of catabolizing AngII. Accordingly, in certain patients with COVID-19 we observed high plasma levels of AngII. When looking for the stimulus responsible for their monocytic ROS production, we revealed that AngII triggers ROS production by monocytes via angiotensin receptor I. ROSs released by AngII-activated monocytes induced DNA damage and apoptosis in neighboring lymphocytes. CONCLUSION: We conclude that T-cell apoptosis provoked via DNA damage due to the release of monocytic ROSs could play a major role in COVID-19 pathogenesis.

Comparative Evaluation of Four Commercially Available Immunoassays for Therapeutic Drug Monitoring of Infliximab and Adalimumab.

Therapeutic drug monitoring (TDM) of anti-TNF-α is an important tool in clinical practice for inflammatory diseases. In this study, we have evaluated the performance of several assays for drug and antidrug antibodies (ADA) measurement in the serum. 50 sera from patients treated with infliximab (IFX) and 49 sera from patients treated with adalimumab (ADAL) were monitored with four immunoassays. We have compared Promonitor, i-Track10®, and ez-track1 assays to our gold standard Lisa Tracker® ELISA using Cohen's kappa, Passing-Bablok, and Bland-Altman analysis. The qualitative analysis evaluated by Cohen's kappa values found for IFX measurements an "almost perfect" concordance for Promonitor, "moderate" for i-Track10® and "substantial" for ez-Track1. For ADAL, kappa values were "moderate" for all tested methods. For anti-IFX, kappa values were "almost perfect" for Promonitor, "fair" for i-Track10®, and "substantial" for ez-Track1. For anti-ADAL, kappa values were "almost perfect" for all three assays. For quantitative analysis of drug measurements, Pearson's r values were all above 0.9 and Lin's concordance coefficients of all immunoassays were around 0.80. Performances of the four evaluated immunoassays were acceptable for TDM based on our laboratory experience. Nevertheless, concordance between the four methods for IFX measurement was not perfect and we recommend the use of the same assay for the follow-up of a given patient. The performances of the four immunoassays evaluated were similar and are acceptable for TDM based on our laboratory experience.

Oleic acid based experimental evolution of Bacillus megaterium yielding an enhanced P450 BM3 variant.

BACKGROUND: Unlike most other P450 cytochrome monooxygenases, CYP102A1 from Bacillus megaterium (BM3) is both soluble and fused to its redox partner forming a single polypeptide chain. Like other monooxygenases, it can catalyze the insertion of oxygen unto the carbon-hydrogen bond which can result in a wide variety of commercially relevant products for pharmaceutical and fine chemical industries. However, the instability of the enzyme holds back the implementation of a BM3-based biocatalytic industrial processes due to the important enzyme cost it would prompt. RESULTS: In this work, we sought to enhance BM3's total specific product output by using experimental evolution, an approach not yet reported to improve this enzyme. By exploiting B. megaterium's own oleic acid metabolism, we pressed the evolution of a new variant of BM3, harbouring 34 new amino acid substitutions. The resulting variant, dubbed DE, increased the conversion of the substrate 10-pNCA to its product p-nitrophenolate 1.23 and 1.76-fold when using respectively NADPH or NADH as a cofactor, compared to wild type BM3. CONCLUSIONS: This new DE variant, showed increased organic cosolvent tolerance, increased product output and increased versatility in the use of either nicotinamide cofactors NADPH and NADH. Experimental evolution can be used to evolve or to create libraries of evolved BM3 variants with increased productivity and cosolvent tolerance. Such libraries could in turn be used in bioinformatics to further evolve BM3 more precisely. The experimental evolution results also supports the hypothesis which surmises that one of the roles of BM3 in Bacillus megaterium is to protect it from exogenous unsaturated fatty acids by breaking them down.

Cytotoxic CD8+ T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons.

Adaptive immune response is part of the dynamic changes that accompany motoneuron loss in amyotrophic lateral sclerosis (ALS). CD4+ T cells that regulate a protective immunity during the neurodegenerative process have received the most attention. CD8+ T cells are also observed in the spinal cord of patients and ALS mice although their contribution to the disease still remains elusive. Here, we found that activated CD8+ T lymphocytes infiltrate the central nervous system (CNS) of a mouse model of ALS at the symptomatic stage. Selective ablation of CD8+ T cells in mice expressing the ALS-associated superoxide dismutase-1 (SOD1)G93A mutant decreased spinal motoneuron loss. Using motoneuron-CD8+ T cell coculture systems, we found that mutant SOD1-expressing CD8+ T lymphocytes selectively kill motoneurons. This cytotoxicity activity requires the recognition of the peptide-MHC-I complex (where MHC-I represents major histocompatibility complex class I). Measurement of interaction strength by atomic force microscopy-based single-cell force spectroscopy demonstrated a specific MHC-I-dependent interaction between motoneuron and SOD1G93A CD8+ T cells. Activated mutant SOD1 CD8+ T cells produce interferon-γ, which elicits the expression of the MHC-I complex in motoneurons and exerts their cytotoxic function through Fas and granzyme pathways. In addition, analysis of the clonal diversity of CD8+ T cells in the periphery and CNS of ALS mice identified an antigen-restricted repertoire of their T cell receptor in the CNS. Our results suggest that self-directed immune response takes place during the course of the disease, contributing to the selective elimination of a subset of motoneurons in ALS.

New Process for the Sulfonation of Algal/PEI Biosorbent for Enhancing Sr(II) Removal from Aqueous Solutions-Application to Seawater.

Sulfonic resins are highly efficient cation exchangers widely used for metal removal from aqueous solutions. Herein, a new sulfonation process is designed for the sulfonation of algal/PEI composite (A*PEI, by reaction with 2-propylene-1-sulfonic acid and hydroxylamine-O-sulfonic acid). The new sulfonated functionalized sorbent (SA*PEI) is successfully tested in batch systems for strontium recovery first in synthetic solutions before investigating with multi-component solutions and final validation with seawater samples. The chemical modification of A*PEI triples the sorption capacity for Sr(II) at pH 4 with a removal rate of up to 7% and 58% for A*PEI and SA*PEI, respectively (with SD: 0.67 g L-1). FTIR shows the strong contribution of sulfonate groups for the functionalized sorbent (in addition to amine and carboxylic groups from the support). The sorption is endothermic (increase in sorption with temperature). The sulfonation improves thermal stability and slightly enhances textural properties. This may explain the fast kinetics (which are controlled by the pseudo-first-order rate equation). The sulfonated sorbent shows a remarkable preference for Sr(II) over competitor mono-, di-, and tri-valent metal cations. Sorption properties are weakly influenced by the excess of NaCl; this can explain the outstanding sorption properties in the treatment of seawater samples. In addition, the sulfonated sorbent shows excellent stability at recycling (for at least 5 cycles), with a loss in capacity of around 2.2%. These preliminary results show the remarkable efficiency of the sorbent for Sr(II) removal from complex solutions (this could open perspectives for the treatment of contaminated seawater samples).

Very high-dose methylprednisolone for treatment of nivolumab-induced limbic encephalitis: A case report.

INTRODUCTION: Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis. CASE REPORT: We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. MANAGEMENT AND OUTCOME: The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. DISCUSSION: Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids.

Risk factors of clinical dysimmune manifestations in a cohort of 86 children with 22q11.2 deletion syndrome: A retrospective study in France.

In this study, we describe the biological immune profiles and clinical dysimmune manifestations (infections, autoimmune diseases, and allergies) of patients with 22q11.2 deletion syndrome with the aim of determining risk factors for clinical events. This retrospective study concerned all the patients with 22q11 deletion syndrome attending the Montpellier University Hospital from January 1, 1992, to December 31, 2014 who had at least one immune investigation before the age of 18. We analyzed the clinical features, biological tests and the course of infections, autoimmunity, and allergy of 86 children. Among these 86 children, 48 (59%) had a low T lymphocyte level. Twenty-nine patients (34%) had a severe infection. The only risk factor for severe infection was the low level of CD4+ T-cells (OR: 3.3; 95% confidence interval (CI) [1.020-11.108]). Eleven patients (13%) developed an autoimmune disease; the only risk factor was an antecedent of severe infection (OR: 4.1; 95% CI [1.099-15.573]). Twenty-three patients (27%) had allergic episodes. A low level of CD8+ T-cells (OR: 3.2; 95% CI [1.07-9.409]) was significantly associated with allergy manifestations. Patients with 22q11 deletion syndrome have a high rate of dysimmune manifestations. We found statistic correlations among CD4+ T-cell count, infectious manifestations, and autoimmunity.

Use of Anti-transcriptional Intermediary Factor-1 Gamma Autoantibody in Identifying Adult Dermatomyositis Patients with Cancer: A Systematic Review and Meta-analysis.

Anti-transcriptional intermediary factor-1γ (TIF-1γ) autoantibody may be associated with cancer in adult patients with dermatomyositis. The aim of this study was to evaluate the risk of cancer in the presence of anti-TIF-1γ autoantibody in adult dermatomyositis. A comprehensive database search of EMBASE, MEDLINE and the Cochrane Library up to May 2018 was performed using the main key words "dermatomyositis", ""myositis", "inflammatory myopathies" and "anti-TIF-1". Eighteen studies, with a total of 1,962 dermatomyositis, were included in the meta-analysis. The pooled prevalence of cancer-associated dermatomyositis in patients with anti-TIF-1γ autoantibody was 0.41 (95% confidence interval (CI) 0.36-0.45). In the presence of anti-TIF-1γ autoantibody, the overall diagnostic odds ratio of cancer was 9.37 (95% CI 5.37-16.34) with low heterogeneity (Cochran's Q: 14.88 (df = 17, p = 0.604); I2 = 0%). The results of this systematic review confirm that detection of anti-TIF-1γ autoantibody is a valuable tool to identify a subset of adult dermatomyositis patients with higher risk of cancer.

Amidoxime Functionalization of Algal/Polyethyleneimine Beads for the Sorption of Sr(II) from Aqueous Solutions.

There is a need for developing new sorbents that incorporate renewable resources for the treatment of metal-containing solutions. Algal-polyethyleneimine beads (APEI) (reinforced with alginate) are functionalized by grafting amidoxime groups (AO-APEI). Physicochemical characteristics of the new material are characterized using FTIR, XPS, TGA, SEM, SEM-EDX, and BET. AO-APEI beads are tested for the recovery of Sr(II) from synthetic solutions after pH optimization (≈ pH 6). Uptake kinetics is fast (equilibrium ≈ 60-90 min). Sorption isotherm (fitted by the Langmuir equation) shows remarkable sorption capacity (≈ 189 mg Sr g-1). Sr(II) is desorbed using 0.2 M HCl/0.5 M CaCl2 solution; sorbent recycling over five cycles shows high stability in terms of sorption/desorption performances. The presence of competitor cations is studied in relation to the pH; the selectivity for Sr(II) is correlated to the softness parameter. Finally, the recovery of Sr(II) is carried out in complex solutions (seawater samples): AO-APEI is remarkably selective over highly concentrated metal cations such as Na(I), K(I), Mg(II), and Ca(II), with weaker selectivity over B(I) and As(V). AO-APEI appears to be a promising material for selective recovery of strontium from complex solutions (including seawater).

Algal Foams Applied in Fixed-Bed Process for Lead(II) Removal Using Recirculation or One-Pass Modes.

The incorporation of brown algae into biopolymer beads or foams for metal sorption has been previously reported. However, the direct use of these biomasses for preparing foams is a new approach. In this study, two kinds of porous foams were prepared by ionotropic gelation using algal biomass (AB, Laminaria digitata) or alginate (as the reference) and applied for Pb(II) sorption. These foams (manufactured as macroporous discs) were packed in filtration holders (simulating fixed-bed column) and the system was operated in either a recirculation or a one-pass mode. Sorption isotherms, uptake kinetics and sorbent reuse were studied in the recirculation mode (analogous to batch system). In the one-pass mode (continuous fixed-bed system), the influence of parameters such as flow rate, feed metal concentration and bed height were investigated on both sorption and desorption. In addition, the effect of Cu(II) on Pb(II) recovery from binary solutions was also studied in terms of both sorption and desorption. Sorption isotherms are well fitted by the Langmuir equation while the pseudo-second order rate equation described well both sorption and desorption kinetic profiles. The study of material regeneration confirms that the reuse of the foams was feasible with a small mass loss, even after 9 cycles. In the one-pass mode, for alginate foams, a slower flow rate led to a smaller saturation volume, while the effect of flow rate was less marked for AB foams. Competitive study suggests that the foams have a preference for Pb(II) over Cu(II) but cannot selectively remove Pb(II) from the binary solution.

Boron removal by a composite sorbent: Polyethylenimine/tannic acid derivative immobilized in alginate hydrogel beads.

A novel composite material was prepared by the grafting of tannic acid on polyethylenimine (PEI), which allows an efficient sorption of boron (sorption capacity close to 0.89 mmol B g-1). The encapsulation of this chelating sorbent (finely crushed) facilitates its use (readily solid/liquid separation, use in fixed-bed columns) at the expense of a loss in sorption capacity (proportionally decreased by the introduction of alginate having poor efficiency for boron uptake). Sorption isotherms are modeled using the Langmuir equation, while the kinetic profiles are presented a good fit by pseudo-second order rate equation. In addition, the encapsulating matrix introduces supplementary resistance to intraparticle diffusion, especially when the resin is dried without control: freeze-drying partially limits this effect. The stability (at long-term storage) of the sorbent is improved when the sorbent is stored under nitrogen atmosphere. The presence of an excess of NaCl was investigated. The degradation of the hydrogel (by ion-exchange of Ca(II) with Na(I)) leads to a decrease in the sorption performance of composite material but the action of Ca(II) ions in the solutions re-stabilizes the hydrogel.

Alginate and Algal-Based Beads for the Sorption of Metal Cations: Cu(II) and Pb(II).

Alginate and algal-biomass (Laminaria digitata) beads were prepared by homogeneous Ca ionotropic gelation. In addition, glutaraldehyde-crosslinked poly (ethyleneimine) (PEI) was incorporated into algal beads. The three sorbents were characterized by scanning electron microscopy (SEM) coupled with energy dispersive X-ray analysis (EDX): the sorption occurs in the whole mass of the sorbents. Sorption experiments were conducted to evaluate the impact of pH, sorption isotherms, and uptake kinetics. A special attention was paid to the effect of drying (air-drying vs. freeze-drying) on the mass transfer properties. For alginate, freeze drying is required for maintaining the porosity of the hydrogel, while for algal-based sorbents the swelling of the material minimizes the impact of the drying procedure. The maximum sorption capacities observed from experiments were 415, 296 and 218 mg Pb g(-1) and 112, 77 and 67 mg Cu g(-1) for alginate, algal and algal/PEI beads respectively. Though the sorption capacities of algal-beads decreased slightly (compared to alginate beads), the greener and cheaper one-pot synthesis of algal beads makes this sorbent more competitive for environmental applications. PEI in algal beads decreases the sorption properties in the case of the sorption of metal cations under selected experimental conditions.

Immobilization of Metal Hexacyanoferrate Ion-Exchangers for the Synthesis of Metal Ion Sorbents--A Mini-Review.

Metal hexacyanoferrates are very efficient sorbents for the recovery of alkali and base metal ions (including radionuclides such as Cs). Generally produced by the direct reaction of metal salts with potassium hexacyanoferrate (the precursors), they are characterized by ion-exchange and structural properties that make then particularly selective for Cs(I), Rb(I) and Tl(I) recovery (based on their hydrated ionic radius consistent with the size of the ion-exchanger cage), though they can bind also base metals. The major drawback of these materials is associated to their nanometer or micrometer size that makes them difficult to recover in large-size continuous systems. For this reason many techniques have been designed for immobilizing these ion-exchangers in suitable matrices that can be organic (mainly polymers and biopolymers) or inorganic (mineral supports), carbon-based matrices. This immobilization may proceed by in situ synthesis or by entrapment/encapsulation. This mini-review reports some examples of hybrid materials synthesized for the immobilization of metal hexacyanoferrate, the different conditionings of these composite materials and, briefly, the parameters to take into account for their optimal design and facilitated use.

Extensive cerebral white matter involvement in a patient with NMO spectrum disorder.

Abnormal brain MRI has been described in up to 60% of patients with NMO patients. However, white matter T2 hyperintensities have been rarely observed. We report the case of a 49-year-old woman with long-lasting neuromyelitis optica (NMO) spectrum disorder and diffuse cerebral white matter T2-weighted hyperintensities. Our case suggests that some NMO patients can progressively develop l extensive cerebral involvement.

Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis.

BACKGROUND: auto-antibodies against the potassium channel inward rectifying potassium channel 4.1 (Kir4.1) have previously been identified in 46% of patients with multiple sclerosis (MS). OBJECTIVES: to confirm these findings. METHODS: we evaluated the presence of anti-Kir4.1 antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence in 268 MS patients, 46 patients with other neurological diseases (OND) and 45 healthy controls. RESULTS: anti-Kir4.1 antibodies were found in 7.5% of MS patients, 4.3% of OND patients and 4.4% of healthy controls. Immunofluorescence analysis did not identify any specific staining. CONCLUSIONS: we confirmed the presence of anti-Kir4.1 antibodies in MS patients, but at a much lower prevalence than previously reported.

TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease.

Since their appearance in the armamentarium for inflammatory bowel disease (IBD) more than a decade ago, antitumor necrosis factor (TNF) inhibitors have demonstrated beneficial activity in induction and maintenance of clinical remission, mucosal healing, improvement in quality of life, and reduction in surgeries and hospitalizations. However, more than one-third of patients present primary resistance, and another one-third become resistant over time. One of the main factors associated with loss of response is the immunogenicity of anti-TNF biologics leading to the production of antidrug antibodies (ADAbs) accelerating their clearance. In this review we present the current state of the literature on the place of TNF and its blockage in the treatment of patients with IBD and discuss the usefulness of serum trough levels and ADAb monitoring in the optimization of anti-TNF therapies.