Relationship between clinical manifestations and serological profile in patients affected by Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies - ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia. Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

Thermal processing of insect allergens and IgE cross-recognition in Italian patients allergic to shrimp, house dust mite and mealworm.

Edible insects are considered as a promising and sustainable alternative protein source for humans, although risk assessments, with particular reference to the allergic potential of insect proteins, are required. Considering that insects are likely to be consumed after processing, it is crucial to assess how processing can influence allergenicity. In our study, we investigated how boiling and frying affect the IgE cross-recognition of proteins from five edible insects (mealworm, buffalo worm, silkworm, cricket and grasshopper). We considered three groups of Italian patients allergic to shrimps and to house dust mites, who had never consumed insects before and two subjects with occupational allergy and food sensitization to mealworm. Our data suggest that thermal processing may change the solubility of proteins, thereby resulting in a protein shift from water-soluble fractions to water-insoluble fractions. Immunoblot and LC-MS/MS analyses have shown that tropomyosin may play an important role as a cross-allergen for house dust mite and shrimp allergic patients, while larval cuticle protein seems to play a major role in the cross-reactivity of patients primarily sensitized to mealworm. On the basis of our results, the effects of processing appear to be protein-, species- and treatment-specific. Therefore, house dust mite, shrimp and mealworm allergic patients should consume insects with caution, even after thermal processing.

Symptomatic cerebrospinal fluid HIV-1 escape with no resistance-associated mutations following low-level plasma viremia.

The majority of neurologically symptomatic cerebrospinal fluid HIV-1 escape cases are connected with resistance-associated mutations and potentially explained by low cerebrospinal fluid antiretroviral concentrations. However, there are still significant knowledge gaps regarding the physiopathology and long-term management of neurosymptomatic viral escape. We report a case of Parkinson-like syndrome following cerebrospinal fluid HIV-1 escape in a 40-year-old female patient with an history of persistent low-level plasma viremia under treatment. No resistance-associated mutations, high viral diversity (env deep sequencing), adequate pharmacokinetics, atypical CD3-CD14-CD4+CD5-CD2-/+CD7-/+ lymphocytes, low-level Epstein-Barr virus replication, and white matter autoimmune reactivity were observed in the cerebrospinal fluid. Antiretroviral regimen modification led to rapid clinical and radiological improvements. This case may increase the current uncertain knowledge on the origin of cerebrospinal fluid HIV-1 and illustrates the consequences of uncontrolled compartmental viral replication; it also highlights the relevance and persistence of immune activation and the possibility of various detrimental mechanisms underlying neurosymptomatic viral escape.

Cerebrospinal fluid viral load and neopterin in HIV-positive patients with undetectable viraemia.

BACKGROUND: Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. The aim of this study was to analyse the prevalence and predictors of non-detectable CSF HIV RNA using a commercial assay. METHODS: In adult HIV-positive HAART-treated patients with confirmed plasma HIV RNA <50 copies/ml, CSF HIV RNA (with Roche Amplicor Assay) and neopterin were measured. RESULTS: 112 adult patients were included. Plasma and CSF HIV RNA were non-detectable (target not detected [TND]) in 29 (25.9%) and 36 (32.1%) patients, respectively. CSF TND was observed more frequently in patients with plasma TND (P=0.005, OR=3.87). CSF neopterin levels were associated with age (rho =0.333, P=0.002) and current (rho= -0.272, P=0.015) and nadir (rho =-0.240, P=0.038) CD4+ T-lymphocytes; the lowest CSF neopterin concentration was observed in patients with CSF TND versus other viral load strata (0.62 mg/dl versus 0.78 mg/dl; P=0.048). CONCLUSIONS: Efficaciously treated HIV-positive patients with detectable plasma HIV RNA might imperfectly control CSF viral replication. Prospective studies addressing the management and neurocognitive consequences of CSF low-level viraemia are warranted.

Diagnostic accuracy of two tests for determination of anti-m2 in the diagnosis of primary biliary cirrhosis: Is it possible to predict the course of the disease?

To evaluate the analytical agreement between results obtained from the indirect immunofluorescence methods and from the multiplexed line-blot assay and EliA-M2, to analyze the diagnostic accuracy in a cohort of primary biliary cirrhosis (PBC) patients and in control patients of two different types of tests for anti-M2 and assess whether, with the advent of a quantitative test, the possibility exists to correlate disease activity with the value of AMA. Serum analysis of 67 patients with fluorescence patterns detected on Hep-2 cells suggestive of PBC-related antibodies and three groups of patients (15 PBC, 16 PBC suspect and 48 disease controls) was carried out. All samples were tested by both a qualitative test multiplexed line-blot Autoimmune Liver Disease Profile Euroline and by a quantitative test EliA-M2 IgG. In order to evaluate a possible correlation between the quantitative M2 and disease activity, we divided patients mixed in a further three groups based on the value EliA-M2. For each of these groups were calculated the average values of the main indices of cholestasis. A perfect agreement was shown between the EliA-M2 and the multiplexed line-blot method for AMA detection. All sera of patients with PBC were positive with both tests, with a 100 % sensitivity. Forty-seven of the 48 sera of the control group were negative for both tests with a 100 % next specificity, and only 70 % for the AMA-IIF. We had also observed in the other three groups of patients that the average of the values of γ-glutamyl transpeptidase and alkaline phosphatase increases with the increase of the value EliA-M2. The difference between the mean values of the most significant parameter which the alkaline phosphatase of the three groups is significant, with a statistically significant difference between the first and the third group (p value 0.023). Both the qualitative method Profile Euroline and the quantitative EliA-M2 have a high diagnostic accuracy for PBC, with a specificity higher than the immunofluorescence method. These preliminary data might suggest the possibility of using the dosage EliA-M2 not only in the diagnosis phase but also in the monitoring of disease activity.

Cerebrospinal fluid biomarkers in patients with plasma HIV RNA below 20 copies/mL.

INTRODUCTION: Low level HIV-1 CSF replication (CsfLLV) is often found even in patients with controlled plasma viraemia. The clinical consequences of such finding are uncertain; however, both symptomatic neurological disturbances and neurocognitive disorders may arise in the context of CSF-escape. Two reports suggested that low level replication in the CSF may be associated with increased CSF neopterine although the impact on other markers of neuroinflammation/damage is currently unknown. MATERIALS AND METHODS: Patients with neurocognitive disorders, new neurological symptoms or followed in longitudinal studies were included provided that they were on HAART, with last available viral load below 20 copies/mL and without central nervous system (CNS)-involving infections/neoplasms. After brain Magnetic Resonance (MR) CSF HIV RNA (CAP/CTM HIV-1 v2.0) and biomarkers [total tau (t-tau), phosphorylated tau (p-tau), 1-42 Beta amyloid (Beta42), neopterine and S100beta] were measured through validated methods. Data are presented as medians (IQR); non-parametric tests are used for all analysis. RESULTS: 70 patients [66.7% male, median age 47.8 years (40-56), median BMI 22.2 kg/m2 (20-24)] were enrolled. Current and nadir CD4+ cell count were 379 (219-656) and 116 cell/mm3 (46-225); HIV RNA was undetectable since 19.7 months (9-53). CSF HIV RNA was undetectable in 24 (34.3%), below 20 copies/mL in 26 (37.1%), above 20 copies/mL in 25 patients [35.7%, median 69 copies/mL (41-134]). Median (IQR) CSF biomarkers values were as follows: t-tau 109 pg/mL (<75-161), p-tau 31.6 pg/mL (23.4-35.4), Beta42 818 pg/mL (623-973), neopterine 0.58 ng/mL (0.45-0.87) and S100beta 149 pg/mL (110-186). Patients with CsfLLV did not show significant differences as for demographic, therapeutic, virological, radiological variables. t-tau (134 vs 92.6, p=0.05) and Beta42 (953 vs 675, p=0.007) were higher in patients with CsfLLV. Neopterine levels were directly associated with p-tau (rho=0.42, p=0.01), with CSF HIV RNA (rho=0.24, p=0.06). and inversely with current CD4 cell count (rho=-0.29, p=03). CONCLUSIONS: In patients with controlled HIV viraemia (below 20 copies/mL), CSF total tau, Beta42 and neopterine were higher in patients with detectable HIV RNA. Prospective and adequately powered studies are warranted for evaluating the clinical significance of compartmental viral replication and immune activation.

Antinuclear antibodies in recurrent idiopathic pericarditis: prevalence and clinical significance.

BACKGROUND: A positive result for antinuclear antibodies (ANA), often as a fortuitous observation, may be cause for concern in idiopathic recurrent pericarditis (IRP), nevertheless data are lacking on their prevalence and clinical significance. This study is sought to investigate the prevalence and clinical significance of ANA in IRP. METHODS: ANA titres were assessed in consecutive patients with recurrent pericarditis, and matched healthy controls. Baseline and follow-up data were recorded and compared according to ANA results. RESULTS: A total of 145 consecutive patients with recurrent pericarditis were studied: 122 patients with IRP, 23 patients with pericarditis due to known etiologies (rheumatologic diagnoses and postpericardiotomy syndrome), and 122 healthy controls. ANA were detected in 53 of 122 (43.4%) patients with IRP, and in only 12 of 122 (9.8%) controls (p<0.001). Low titres (1/40-1/80) were found in the majority of cases, while moderate positivity (1/160-1/320) was more common in patients with a known rheumatic disease (26.7% vs. 5.7%; p=0.020). High concentrations of ANA (> or =1/640) were not recorded. Women were at increased risk for ANA (OR 2.22 95%CI 1.07-4.60; p=0.033). During a mean follow-up of 32 months, complications and new diagnoses were similar in patients with or without ANA positivity. CONCLUSIONS: Low-positive titres are more common in patients with IRP than in controls, suggesting a possible autoimmune pathogenesis. Nevertheless, they are often a clinically non-specific finding. Routine serologic testing for ANA suggests a source for recurrent pericarditis in less than 10% of cases, and in these cases other evidence typically suggests the underlying disease.