How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative

Immunologic Research - Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a...     

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico

Journal of Clinical Immunology - Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe...     

The effect of desire thinking on facilitating beliefs in alcohol use disorder: An experimental investigation

Permissive beliefs relate to the acceptability of engaging in alcohol use in spite of obvious potential negative consequences. They are considered the most proximal and precipitating cognitive factor in the decision to use alcohol and/or the activation of strategies to obtain it. Recent research suggested that ‘desire thinking’ may be involved in the escalation of craving and addictive behaviours and can play a role in strengthening permissive beliefs. The current study tested whether the induction of desire thinking would have a stronger effect on rate of conviction in permissive beliefs compared to a control cognitive response in the form of neutral thinking and whether this effect would be specific for patients with alcohol use disorder (AUD). Thirty AUD patients and 30 social drinkers (SD) were randomly allocated to two thinking manipulation tasks (desire thinking and neutral thinking). Current permissive beliefs were measured before and after manipulation and after a resting phase. Findings showed that desire thinking increased the level of current permissive beliefs after manipulation relative to the neutral thinking condition for the AUD group but not for the SD group. This effect was not purely dependent on the concurrent level of perceived craving. This study supports a causal relationship between the induction of desire thinking and rate of conviction in permissive beliefs and highlights the relevance of targeting desire thinking in the treatment for AUD patients.     

Evaluation of the commercial AD fosfomycin test for susceptibility testing of multidrug-resistant Enterobacterales and Pseudomonas aeruginosa

ObjectivesTo compare fosfomycin susceptibility testing with the commercial agar dilution (AD) test, AD Fosfomycin (Liofilchem, Roseto degli Abruzzi, Italy) and the reference AD method, using a collection of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa clinical isolates.MethodsThe collection included 119 carbapenemase-producing Enterobacterales, 53 Enterobacterales producing acquired AmpC-type and/or extended-spectrum β-lactamases and 38 carbapenemase-producing P. aeruginosa, including representatives of different high-risk clones. AD Fosfomycin and AD reference method (ISO 20776-1:2019) were performed starting from the same microbial suspension. Results were interpreted according to EUCAST clinical breakpoints (10.0). Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization.ResultsOf 172 Enterobacterales, 143 (83.1%, including 92.9% (52 of 56) of the NDM-producers and 84.2% (48 of 57) of the KPC-producers) were susceptible to fosfomycin using reference AD. A CA of 91.9% (158 of 172; 95% CI 87.1%–95.3%) and an EA of 92.5% (136 of 147; 95% CI 87.4%–96.0%), respectively, were calculated for the commercial AD Fosfomycin test, with 9.8% (14 of 143) of major errors and no very major errors (0 of 29). Overall, 86.8% (33 of 38) of P. aeruginosa showed a fosfomycin MIC ≤128 mg/L using reference AD. An EA of 84.8% (95% CI 66.3%–92.0%) was calculated for the commercial AD Fosfomycin test, with a CA of 100% (95% CI 93.6%–100%) when considering a tentative breakpoint at 128 mg/L.ConclusionsAD Fosfomycin showed an overall good concordance compared with reference AD.     

JAK inhibitors and psoriatic arthritis: A systematic review and meta-analysis

BackgroundDespite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, additional drugs are needed to improve care of this disease. JAK inhibitors (JAKinhibs) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA. Tofacitinib and Upadacitinib were recently approved for the treatment of PsA. Our aim was to assess the efficacy and safety of JAKinhibs for the treatment of PsA.MethodsA systematic review of the literature was performed to identify RCTs by electronic search of MEDLINE and EMBASE database until April 2021. RCTs were considered eligible if included only patients with PsA treated with JAKinhibs. The pooled efficacy and safety outcomes were calculated by meta-analysis and expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I² statistic.ResultsFive RCTs for a total of 3293 PsA patients treated with different JAKinhibs or placebo were included (2 phase III studies on Tofacitinib, 1 phase II study on Filgotinib and 2 phase III studies on Upadacitinib). All the studies were judged at low risk of bias according to Cochrane criteria. JAKinhibs showed a significantly higher ACR20 response rate compared to placebo (OR 3.78, 95% CI 2.72–5.24, I^2 = 57%, random effect model).and were associated with a non-statistically significant higher risk of serious adverse events (OR 1.12, 95% CI 0.14–2.82, I^2 = 46%, random effect model).ConclusionsThis is the first systematic review that performed a comprehensive evaluation of the efficacy and safety of JAKinhibs for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKinhibs that appear to be effective and safe over placebo for the treatment of PsA.     

Autoimmunity and cancer

In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. The link between autoimmunity and cancer is dynamic and bidirectional. Recent advances in terms of knowledge of biology, epidemiology, and long-term outcomes for the autoimmune rheumatic diseases have revealed several new connections between these two entities. Data suggest that chronic inflammation from the rheumatic diseases or their therapies may contribute to the onset and promotion of cancer. Conversely, antitumor immune responses may become cross-reactive with self-tissues resulting in the development of autoimmunity. In this review, we discuss about the potential mechanisms that link autoimmune rheumatic diseases and cancer and the association of malignancies with common autoimmune disorders. The increased incidence of malignancy in autoimmune rheumatic diseases has been largely described, although the biology underpinning this relationship should be further investigated. The development of evidence-based cancer screening recommendations in patients with autoimmune rheumatic diseases is complex due to the heterogeneity of clinical rheumatic phenotypes, cancer sites at risk and exposure to anti-neoplastic and anti-rheumatic treatment. In order to lay the foundation of risk stratification and targeted cancer screening, larger longitudinal cohort studies that provide a more detailed framework of the links between cancer and autoimmunity are urgently needed.     

The biology,pathogenetic role,clinical implications,and open issues of serum anti-neutrophil cytoplasmic antibodies

Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies, predominantly IgG, involved in the pathogenesis of several autoimmune disorders, detected either through indirect immunofluorescence or enzyme-linked immunosorbent assay. By means of indirect immunofluorescence, the main patterns are C-ANCA (cytoplasmic) and P-ANCA (perinuclear), while proteinase 3 (PR3) and myeloperoxidase (MPO) represent the main autoantigens in granulomatosis with polyangiitis and microscopic polyangiitis, both belonging to the family of ANCA-associated vasculitis (AAV). While several experiments established the pathogenicity of MPO-ANCA, evidence remains elusive for PR3-ANCA and an additional target antigen, i.e. LAMP2, has been postulated with specific clinical relevance. The presence of a subset of AAV without ANCA may be explained by the presence of further target antigens or the presence of molecules in blood which make ANCA undetectable. A rise in ANCA titers is not necessarily predictive of a flare of disease in AAV if not accompanied by clinical manifestations. ANCA may develop through variable mechanisms, such as autoantigen complementarity, apoptosis impairment, neutrophil extracellular traps dysfunction and molecular mimicry. We will provide herein a comprehensive review of the available evidence on the biological mechanisms, pathogenetic role, and clinical implications of ANCA testing and disease management. Further, we will address the remaining open challenges in the field, including the role of ANCA in inflammatory bowel disease and in cocaine-induced vasculitis.     

Circulating prostaglandin E2: a novel potential prognostic biomarker in patients with hepatocellular carcinoma

Clinical and Experimental Medicine - We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC),...     

When Old Meets New: Emotion Recognition from Speech Signals

Cognitive Computation - Speech is one of the most natural communication channels for expressing human emotions. Therefore, speech emotion recognition (SER) has been an active area of research with...     

Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.