Newer Autoantibodies and Laboratory Assessments in Myositis.

Purpose Of Review: We aim to describe the immunoassays that have been used for myositis autoantibody discovery with a focus on newer methods. We describe recently identified myositis autoantibodies that do not yet form part of routine clinical testing, highlighting what is known about their associated clinical phenotype and potential clues as to their presence.

Recent Findings: Novel approaches to autoantibody detection have been employed in recent years including chemiluminescent immunoassay, phage immunoprecipitation-sequencing and modifications to the more traditional immunoprecipitation technique.

Anti-Sp4 and Anti-CCAR1 autoantibodies in UK vs. US patients with adult and juvenile-onset anti-TIF1Æ´-positive myositis.

Objectives: Anti-TIF1γ autoantibodies are associated with malignancy in adult-onset idiopathic inflammatory myopathy (IIM) and this risk is attenuated if patients are also positive for anti-specificity protein 4 (Sp4) or anti-cell division cycle apoptosis regulator protein 1 (CCAR1). In anti-TIF1γ positive US dermatomyositis (DM) patients, anti-Sp4 and anti-CCAR1 autoantibody frequencies are reported as 32% and 43% in adults and 9% and 19% in juveniles, respectively. This study aims to identify the frequency of anti-Sp4 and anti-CCAR1 in adult and juvenile UK anti-TIF1ƴ-positive myositis populations and report clinical associations.

Autoantibody testing in myositis: an update.

Purpose Of Review: This review aims to provide an update on myositis autoantibody testing strategies. We have focussed on the reliability and usefulness of different myositis autoantibody detection methods, including commonly used solid phase immunoassays and newer discovery techniques.

Recent Findings: Several studies have highlighted the limitations of currently available immunoassays, particularly when used in populations with low pretest probability and without supporting clinical evidence.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

Background: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD.

Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.

Objectives: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort.

Methods: Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow.

Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

Objectives: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ.

Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies.

Background: In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM.

Methods: We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies.

Incidence of giant cell arteritis is associated with COVID-19 prevalence: A population-level retrospective study.

Background: Following the first wave of the COVID-19 pandemic, it was observed that giant cell arteritis (GCA) diagnoses increased at the Royal National Hospital for Rheumatic Diseases (RNHRD) in Bath, UK. This finding may support the viral aetiology hypothesis of GCA. Better understanding of the causes of GCA may help improve diagnostic and treatment strategies leading to better outcomes for patients.

Health outcomes of penicillin allergy testing in children: a systematic review.

Background: Penicillin allergy labels are commonly acquired in childhood and lead to avoidance of first-line penicillin antibiotics. Understanding the health outcomes of penicillin allergy testing (PAT) can strengthen its place in antimicrobial stewardship efforts.

Objectives: To identify and summarize the health outcomes of PAT in children.

Monoaminergic mediation of hyperalgesic and analgesic descending control of nociception in mice.

Descending control of nociception (DCN; also known as conditioned pain modulation [CPM], the behavioral correlate of diffuse noxious inhibitory controls) is the phenomenon whereby pain inhibits pain in another part of the body and is the subject of increasing study because it may represent a biomarker of chronic pain. We recently discovered that pain modulation on the application of a DCN paradigm involving low-intensity test stimuli occurs in the direction of hyperalgesia in healthy mice and rats, whereas the use of high-intensity stimuli produces analgesia. To elucidate the physiological mechanisms underlying hyperalgesic DCN, we administered agonists and antagonists of norepinephrine (NE) and serotonin (5-HT) receptors, key neurochemical players in the production of analgesic DCN.

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population.

Background: The reliable detection of myositis-specific autoantibodies (MSA) provides valuable clinical information regarding prognosis, clinical progression and diagnostic confirmation.

Objectives: To evaluate the reliability of a commercial ELISA immunoassay in detecting myositis-specific autoantibodies in comparison to immunoprecipitation as the reference standard.

Methods: Serum samples were chosen from a biobank of more than 3000 samples.

Microglia-mediated degradation of perineuronal nets promotes pain.

Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn.

Olfactory exposure to late-pregnant and lactating mice causes stress-induced analgesia in male mice.

In an attempt to improve reproducibility, more attention is being paid to potential sources of stress in the laboratory environment. Here, we report that the mere proximity of pregnant or lactating female mice causes olfactory-mediated stress-induced analgesia, to a variety of noxious stimuli, in gonadally intact male mice. We show that exposure to volatile compounds released in the urine of pregnant and lactating female mice can themselves produce stress and associated pain inhibition.

mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation.

The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. Tissue inflammation, by changing the intrinsic properties of the nociceptive endings, leads to nociceptive hyperexcitability and thus to the development of inflammatory pain. Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain.

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence.

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing.

A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing.

Objectives: Anti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ.

4E-BP2-dependent translation in parvalbumin neurons controls epileptic seizure threshold.

The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as , , , , and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models with elevated mTORC1 activity.