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Background COVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection. Methods The cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto’s disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case–control study, a case–control with test-positive as cases, and one with test-negative as cases (CC-NEG). Results During the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested. Conclusions Lack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.

to describe an innovative algorithm to classify the general population, in homogeneous groups of severity and complexity of disease and real needs, by using three dimensions: health, frailty, and disability.retrospective cohort study.the study includes the population covered by the Agency for health protection of Metropolitan Area of Milan (3,4 million of habitants). We identified two cohorts of residents: the first at 01.01.2015 and the second at 01.01.2016, classified in four different and mutually exclusive groups based on health and social data of the previous year.we estimated prevalence by age of the four main groups and we studied the transition, observed among groups, from 2015 to 2016. The algorithm validation was performed using non-conditional logistic regression+R14 models to estimate the association with total mortality with increasing levels of severity through the odds ratio (OR) and corresponding 95% confidence intervals (95%CI). The model performance, i.e., its predictive power and calibration, was evaluated by means of C-index and Hosmer-Lemeshow test, respectively.a total of 19% of subjects is healthy (group A); 41.6% has non-specific access to the health regional system (group B); 17% is a vulnerable (group C); and 22% has a chronic condition (group D). Combining chronic conditions with the frailty level, we classified population into subgroups. The risk of death within a year increases linearly in relation with increasing complexity of the health category and frailty level, with a grow of estimates from 0.83 to 135.6, using the healthy subjects as reference. The evaluation of the overall predictive power of the model, calculated by the C-index, shows a value of 0.94. The calibration of the model evaluated using the Hosmer-Lemeshow test returns a value of 327.2 (χ2 8 df, p-value0.0001), underestimating the expected in the first three deciles and overestimating in the last deciles.the algorithm classify general population in homogeneous groups allowing to develop taking care models allocating health resources based on the real needs of patients.

to figure out if there are differences in access to psychiatric services between Italian and immigrant paediatric populations.we analysed the data of the year 2012 from the Banca dati del disagio psichico, a database on psychological distress created by the Epidemiological Unit of the Local Health Unit Milan 1 (Lombardy, Northern Italy). The database is based on a data warehouse system that integrates health and social data, and gives the opportunity to calculate the prevalence rates of the main clusters of psychiatric diseases according to ICD-10 categories.the sample includes 162,197 residents younger than 18 years (minors), divided into 4 subgroups depending on the place of birth (Italy or abroad) and citizenship (Italian or foreign).we calculated the standardised treated prevalence of the 11 clusters of mental diseases in the 4 subgroups and evaluated the Standardised Prevalence Ratio (SPR) and their confidence intervals using as reference the Italian paediatric population with Italian citizenship.in 2012, 7.2%minors were diagnosed a mental illness or accessed mental health services or were prescribed psychotropic medicines. We found the lowest SPRs of psychiatric illnesses in immigrants (0.91 born in Italy; 0.74 born abroad) and the higher in Italians born in foreign Countries (1.34). In particular, migrant minors born in Italy have lower SPR of developmental disorders (0.84) and behaviour and emotional disorders (0.68), but higher SPR of mental retardation (1.52) and anxiety disorders (1.36). Migrant minors born abroad have lower SPR of developmental disorders (0.52), but higher rates of mental retardation (1.30). Italians born in foreign Countries show a SPR for personality disorders and mental retardation of 4.86 and 2.02, respectively.immigrant minors have a lower prevalence of psychiatric diseases than Italian minors; however, Italians born in foreign Countries show a higher prevalence of psychiatric disorders.

We evaluated oligoclonal IgG band (OCB) patterns obtained by analyzing paired cerebrospinal fluid (CSF) and serum samples of 77 patients with acute demyelinating encephalomyelitis (ADEM) and 411 patients with multiple sclerosis (MS). OCBs were searched with isoelectric focusing and capillary immunoblotting. CSF-restricted OCBs were found in 89% of MS patients and 10% of ADEM patients (p

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8+ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.

Intracellular cytokine flow cytometry was used to analyse the percentages of interferon (IFN) gamma and interleukin (IL)-4 producing T cells in the peripheral blood of multiple sclerosis patients, before and after immunomodulatory treatment, and of healthy controls. After six months of treatment, different doses of IFN beta1a (Avonex or Rebif) decreased CD4+ (Th1, Th2) and CD8+ (Tc1) cells to a similar extent, without affecting the Th1/Th2 ratio. These T cell subsets were unmodified after nine months of glatiramer acetate (Copaxone) treatment, and after six day courses of high dose 6-methylprednisolone. The data suggest that IFN beta1a produces sustained downmodulation of IFN gamma and IL-4 producing T cells in vivo, which may contribute to its therapeutic efficacy; that glatiramer acetate possibly acts without altering non-specific cellular immunity; and that glucocorticoid induced lymphocytopenia does not affect the percentages of Th1, Th2, and Tc1 cells; at least in the periphery, none of the treatments caused a Th1 to Th2 shift that could account for their respective therapeutic effects.

Corrigendum to “Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease” [Neurobiol. Dis. 41/2 (2011) 508–527] F. L'Episcopo , C. Tirolo , N. Testa , S. Caniglia , M.C. Morale , C. Cossetti , P. D'Adamo , E. Zardini , L. Andreoni , A.E.C. Ihekwaba , P.A. Serra , D. Franciotta , G. Martino , S. Pluchino , B. Marchetti a,g,h,⁎

Emerging evidence points to reactive glia as a pivotal factor in Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of basal ganglia injury, but whether astrocytes and microglia activation may exacerbate dopaminergic (DAergic) neuron demise and/or contribute to DAergic repair is presently the subject of much debate. Here, we have correlated the loss and recovery of the nigrostriatal DAergic functionality upon acute MPTP exposure with extensive gene expression analysis at the level of the ventral midbrain (VM) and striata (Str) and found a major upregulation of pro-inflammatory chemokines and wingless-type MMTV integration site1 (Wnt1), a key transcript involved in midbrain DAergic neurodevelopment. Wnt signaling components (including Frizzled-1 [Fzd-1] and β-catenin) were dynamically regulated during MPTP-induced DAergic degeneration and reactive glial activation. Activated astrocytes of the ventral midbrain were identified as candidate source of Wnt1 by in situ hybridization and real-time PCR in vitro. Blocking Wnt/Fzd signaling with Dickkopf-1 (Dkk1) counteracted astrocyte-induced neuroprotection against MPP(+) toxicity in primary mesencephalic astrocyte-neuron cultures, in vitro. Moreover, astroglial-derived factors, including Wnt1, promoted neurogenesis and DAergic neurogenesis from adult midbrain stem/neuroprogenitor cells, in vitro. Conversely, lack of Wnt1 transcription in response to MPTP in middle-aged mice and failure of DAergic neurons to recover were reversed by pharmacological activation of Wnt/β-catenin signaling, in vivo, thus suggesting MPTP-reactive astrocytes in situ and Wnt1 as candidate components of neuroprotective/neurorescue pathways in MPTP-induced nigrostriatal DAergic plasticity.

Contains fulltext : 89601.pdf (Publisher’s version ) (Closed access) BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p

Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series.

Objective – Paired serum and cerebrospinal fluid (CSF) specimens were investigated for Chlamydia pneumoniae-specific oligoclonal bands (OCBs) to determine band specificity in multiple sclerosis (MS). Material and methods – Serum and CSF samples were collected from patients with relapsing–remitting MS (n = 56), other inflammatory (n = 18) or non-inflammatory (n = 15) neurologic diseases, and from 10 healthy controls. OCBs were determined with affinity immunoblotting of C. pneumoniae-specific IgG onto antigen-coated nitrocellulose paper after protein separation with agarose isoelectric focusing. Results – Chlamydia pneumoniae-specific OCBs were present in 5 of 56 patients with MS, and in 3 of 18 patients with other inflammatory neurologic diseases. Conclusions – The intrathecal production of C. pneumoniae-specific oligoclonal IgG occurs in a minority of patients with MS. This intrathecal anti-C. pneumoniae reactivity is likely part of a polyspecific humoral immune response in MS.

Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-γ- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-γ-producing CD4 + and CD8 + T cells (IFGCs), namely Th1 (mean, 21.4 ± S.D. 1.3) and Tc1 (12.6 ± 1.1), and the Th1/Th2 ratio (6.1 ± 0.2) in DS were significantly higher than in MR (15.9 ± 1.3, 7.9 ± 0.6, 4.8 ± 0.3) and in HCs (15.6 ± 1.9, 7.2 ± 1.1, 4.6 ± 0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.

The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma -interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly Lower in acute MS [468 +/- (S.E.M.) 18 pg/ml] than in stable MS (857 +/- 104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331 +/- 66 pg/ml; CSF 118 +/- 16 pg/ml) than in stable MS (serum 69 +/- 7 pg/ml; CSF 25 +/- 2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta 1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS. and these variations are inverse: and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10. (C) 2001 Elsevier Science B.V. All rights reserved.