Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy.

BACKGROUND: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking. OBJECTIVES: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls. METHODS: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection. RESULTS: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases. CONCLUSIONS: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Population-based incidence rates of 15 neuromuscular disorders: a nationwide capture-recapture study in the Netherlands.

Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders.

TCRß clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity.

Objectives: To characterize the T cell receptor (TCRß) repertoire in peripheral blood and muscle tissues of treatment naïve patients with newly diagnosed idiopathic inflammatory myopathies (IIMs). Methods: High throughput RNA sequencing of the TCRß chain was performed in peripheral blood and muscle tissue in twenty newly-diagnosed treatment-naïve IIM patients (9 DM, 5 NM/OM, 5 IMNM and 1 ASyS) and healthy controls. Results thereof were correlated with markers of disease activity. Results: Muscle tissue of IIM patients shows more expansion of TCRß clones and decreased diversity when compared to peripheral blood of IIM as well as healthy controls (both p=0.0001). Several expanded TCRß clones in muscle are tissue restricted and cannot be retrieved in peripheral blood. These clones have significantly longer CDR3 regions when compared to clones (also) found in circulation (p=0.0002), while their CDR3 region is more hydrophobic (p<0.01). Network analysis shows that clonal TCRß signatures are shared between patients. Increased clonal expansion in muscle tissue is significantly correlated with increased CK levels (p=0.03), while it tends to correlate with decreased muscle strength (p=0.08). Conclusion: Network analysis of clones in muscle of IIM patients shows shared clusters of sequences across patients. Muscle-restricted CDR3 TCRß clones show specific structural features in their T cell receptor. Our results indicate that clonal TCRß expansion in muscle tissue might be associated with disease activity. Collectively, these findings support a role for specific clonal T cell responses in muscle tissue in the pathogenesis of the IIM subtypes studied.