IgG and IgA autoantibodies against L1 ORF1p expressed in granulocytes correlate with granulocyte consumption and disease activity in pediatric systemic lupus erythematosus

BACKGROUND: Most patients with systemic lupus erythematosus (SLE) have IgG autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement. This study tested if these autoantibodies are also present in children with pediatric SLE (pSLE) and if the p40 protein itself could be detected in immune cells. METHODS: Autoantibodies in the plasma of pSLE patients (n = 30), healthy children (n = 37), and disease controls juvenile idiopathic arthritis (JIA) (n = 32) and juvenile dermatomyositis (JDM) (n = 60), were measured by ELISA. Expression of p40 in immune cells was assessed by flow cytometry. Markers of neutrophil activation and death were quantitated by ELISA. RESULTS: IgG and IgA autoantibodies reactive with p40 were detected in the pSLE patients, but were low in healthy controls and in JIA or JDM. pSLE patients with active disease (13 of them newly diagnosed) had higher titers than the same patients after effective therapy (p = 0.0003). IgG titers correlated with SLEDAI (r = 0.65, p = 0.0001), ESR (r = 0.43, p = 0.02), and anti-dsDNA antibodies (r = 0.49, p < 0.03), and inversely with complement C3 (r = -0.55, p = 0.002) and C4 (r = -0.51, p = 0.006). p40 protein was detected in a subpopulation of CD66b(+) granulocytes in pSLE, as well as in adult SLE patients. Myeloperoxidase and neutrophil elastase complexed with DNA and the neutrophil-derived S100A8/A9 were elevated in plasma from pSLE patients with active disease and correlated with anti-p40 autoantibodies and disease activity. CONCLUSIONS: Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, and this protein can be detected in circulating granulocytes in both pediatric and adult SLE patients. P40 expression and autoantibody levels correlate with disease activity. Markers of neutrophil activation and death also correlate with these autoantibodies and with disease activity, suggesting that neutrophils express L1 and are a source of p40. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-021-02538-3

Combining sequencing approaches to fully resolve a carbapenemase-encoding megaplasmid in a Pseudomonas shirazica clinical strain

ABSTRACTHorizontal transfer of plasmids plays a pivotal role in dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Plasmid sequencing is thus paramount for accurate epidemiological tracking in hospitals and routine surveillance. Combining Nanopore and Illumina sequencing allowed full assembly of a carbapenemase-encoding megaplasmid carried by multidrug-resistant clinical isolate FFUP\_PS\_41. Average nucleotide identity analyses revealed that FFUP\_PS\_41 belongs to the recently proposed new species Pseudomonas shirazica, related to the P. putida phylogenetic group. FFUP\_PS\_41 harbours a 498,516-bp megaplasmid (pJBCL41) with limited similarity to publicly-available plasmids. pJBCL41 contains genes predicted to encode replication, conjugation, partitioning and maintenance functions and heavy metal resistance. The |aacA7|blaVIM-2|aacA4| cassette array (resistance to carbapenems and aminoglycosides) is located within a class 1 integron that is a defective Tn402 derivative. This transposon lies within a 50,273-bp region bound by Tn3-family 38-bp inverted repeats and flanked by 5-bp direct repeats (DR) that composes additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach allowed full resolution of a carbapenemase-encoding megaplasmid from P. shirazica. Identification of novel megaplasmids sheds new light on the evolutionary effects of gene transfer and the selective forces driving antibiotic resistance

A pine butterfly impact survey on the Bitterroot National Forest and state of Montana lands, 1972

The pine butterfly, Neophasia menapia (Felder and Felder), currently is epidemic on approximately 40,000 acres of State, private, and National Forest land in the Bitter Root Valley. Butterfly populations were reported as becoming epidemic in 1969 and have continually increased to the present level (Bousfield and Dewey 1972). Because this is the first documented pine butterfly outbreak in Montana, we are uncertain how damaging it might be before it subsides. Two studies in southern and central Idaho have measured the impact of pine butterfly outbreaks on mature ponderosa pine. Both studies were rather limited in their scope

Status of the western hemlock looper in the northern region, 1972

Over 10,000 acres of aerially visible western hemlock looper defoliation on grand fir was detected on State and Federal forests of central Idaho in 1972. This is the first report of this insect building up in Region 1 since a widespread outbreak in 1937-39. The western hemlock looper has the potential of being one of the most destructive forest insects in North America. It can cause tree mortality in 1 or 2 years of feeding. Extensive tree mortality has been associated with nearly all past outbreaks. Outbreaks usually persist for about 3 years at epidemic levels prior to collapsing from natural control agents. Insecticides have been effective in protecting large stands during some looper infestations

Evaluation of mountain pine beetle infestations, Gallatin Ranger District, Gallatin National Forest, Montana, 1975

Mountain pine beetle has occurred at epidemic level in lodgepole pine stands in the west Gallatin River drainage since 1969. Infestation now encompasses about 5,500 acres. Since 1969, approximately 463,212 trees, with an estimated volume of 20,529,244 board feet have been killed. Approximately 69 percent of the stands on the Gallatin District are classed as susceptible. It is predicted that about 927,781 trees will be killed in 1976. Selective logging to remove infested and susceptible trees is recommended to reduce the potential for a continued epidemic

Sighting acute myocardial infarction through platelet gene expression

© 2019, The Author(s). Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs

Mental health in paediatric and adult myositis-related diseases : current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking. Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention