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The prevalence of autoimmune diseases (AIDs) ranges from 3.2% to 9.4% and continues to increase. (1-3) Antinuclear antibodies (ANAs), which target specific cellular constituents, are commonly used in clinical practice. [...], * Context.--Antinuclear antibodies (ANAs) against certain antigens are useful for identifying autoimmune disorders. Although new solid phase-based immunoassays have been developed for evaluating ANAs, the conventional line immunoassay (LIA) is commonly used in clinical practice. Objective.--To compare the clinical performance of 2 newly developed methods for detecting specific ANAs with LIA. Design.--Six hundred ninety-six serum samples were collected from 559 patients with autoimmune disease (AID) and 137 controls. The samples were screened by using the LIA, digital liquid chip method (DLCM), and chemiluminescent immunoassay (CLIA) for specific ANAs. The agreement across assays and the clinical performance of each assay in diagnosing ANA-associated rheumatic diseases (AARDs) were evaluated. Results.--Almost perfect agreement was observed among all assays for anti-centromere protein B ([kappa] = 0.85-0.97), anti-ribosome P ([kappa] = 0.85-0.88), anti-SSA 52 ([kappa] = 0.86-0.89), and anti-SSA 60 ([kappa] = 0.89-0.91); moderate to substantial agreement was detected for the autoantibodies against Sm, Jo-1, ribonucleoprotein, Scl-70, and SSB ([kappa] = 0.55-0.80). LIA exhibited better sensitivity for diagnosing AARDs, while DLCM and CLIA demonstrated higher specificity. In the subset of AIDs, especially systemic lupus erythematosus, antibody positive percentages varied greatly between assays. Conclusions.--The 3 assays showed comparable qualitative agreement; however, the standardization of testing for ANAs remains challenging owing to intermanufacturer variations. Moreover, DLCM and CLIA exhibited better specificity in distinguishing non-AID individuals, whereas LIA was more sensitive in diagnosing AARDs.

Introduction Glioblastoma (GBM) is an aggressive and malignant brain tumor that arises from glial cells (1). GBM is one of the most common and deadly forms of brain cancer in [...], Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the [B.sub.Vax] (B cell- based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aimed to characterize the antigenic reactivity of [B.sub.Vax]-derived Abs and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and samples from patients with GBM. Our investigations revealed that [B.sub.Vax] distributed throughout the GBM tumor microenvironment and then differentiated into Ab-producing plasmablasts. Proteomics analyses indicated that the Abs produced by [B.sub.Vax] had unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these Abs inhibited critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of [B.sub.Vax]-derived Abs for patients with GBM, pointing toward a novel direction for GBM immunotherapy.

Author(s): Reena K. Sharma [1]; Mudita Gupta (corresponding author) [2] Introduction Systemic sclerosis (SSc) is a generalized disorder characterized by small vessel vasculopathy, autoantibody production, and fibrosis of multiple systems [...], Background: Systemic sclerosis is an autoimmune connective tissue disease characterized by fibrosis in skin and internal organs. Chronic exposure to silica may not only lead to silicosis of lungs but also systemic sclerosis. Systemic sclerosis is relatively commoner in females; however, occupational exposure to silica in males makes them vulnerable to silica--associated systemic sclerosis (Erasmus syndrome). Objective: To describe the clinico-epidemiological aspects of systemic sclerosis in males in a retrospective cohort study. Materials and Methods: The data were analysed retrospectively for demographic profile and clinical characteristics including examination findings, laboratory investigations, and treatments of all male patients diagnosed with systemic sclerosis with or without silica exposure, managed from January 2018 to December 2021. Results: Eight out of twelve patients were having silica exposure in the form of stone cutting, cement exposure, and working with concrete. The average age was 55 ± 10.72 years with average smoking exposure of around 24.4 ± 12.8 pack years. Skin thickening was reported by all patients with an average modified Rodnan score of 18.33/51 in diffuse and 7/51 in limited cutaneous systemic sclerosis. Raynaud's phenomenon and sclerodactyly were universal findings, while 9 (75) patients had digital pitted scars. Antinuclear antibodies were present in all patients and specific antibodies substantiated the clinical assessment in almost all patients. Interstitial lung disease was the most common systemic finding present in 11 (91) patients and tuberculosis was diagnosed in 2 (25) cases with silica exposure. Gastrointestinal and cardiac system involvement was seen in 5 (41.6) and 4 (33.3) patients, respectively. Conclusion: Systemic sclerosis in males against the gender predilection indicates the role of occupational exposure. Silicosis and systemic sclerosis synergistically add to lung damage, and at the same time, these patients are more prone to infections like tuberculosis. Keywords: Erasmus syndrome, systemic sclerosis, and silicosis

Introduction Viral pathogens such as flaviviruses, coronaviruses, and influenza viruses pose unique challenges for adaptive immune responses because of the existence of many serotypes and/or the frequent emergence of new [...], NKT cells are innate-like T cells, recruited to the skin during viral infection, yet their contributions to long- term immune memory to viruses are unclear. We identified granzyme K, a product made by cytotoxic cells including NKT cells, as linked to induction of Th1-associated antibodies during primary dengue virus (DENV) infection in humans. We examined the role of NKT cells in vivo using DENV-infected mice lacking CD1d-dependent ([CD1d.sup.dep]) NKT cells. In CD1d-KO mice, Th1- polarized immunity and infection resolution were impaired, which was dependent on intrinsic NKT cell production of IFN- [gamma], since it was restored by adoptive transfer of WT but not IFN-[gamma]-KO NKT cells. Furthermore, NKT cell deficiency triggered immune bias, resulting in higher levels of Th2-associated IgG1 than Th1-associated IgG2a, which failed to protect against a homologous DENV rechallenge and promoted antibody-dependent enhanced disease during secondary heterologous infections. Similarly, Th2 immunity, typified by a higher IgG4/IgG3 ratio, was associated with worsened human disease severity during secondary infections. Thus, [CD1d.sup.dep] NKT cells establish Th1 polarity during the early innate response to DENV, which promotes infection resolution, memory formation, and long-term protection from secondary homologous and heterologous infections in mice, with consistent associations observed in humans. These observations illustrate how early innate immune responses during primary infections can influence secondary infection outcomes.

I was a keen first-year medical student in Kuala Lumpur, standing in a pediatric bay. 'Isles of white in a sea of red,' my consultant said while inspecting the child's [...]

Introduction Autoantibodies have been identified in a wide range of autoimmune diseases (1-4). In many cases these autoantibodies are directly pathogenic (5-10), while in others they amplify or support T [...], Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human-derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B cell maturation antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and anti-CD20 therapies had minimal effects. These data both confirm that the autoreactome comprises autoantibodies secreted by plasma cells and strongly suggest that BCMA or other plasma cell- targeting therapies may be highly effective in treating currently refractory autoantibody-mediated diseases.

Author(s): Clarkson Crane [sup.1] , Erin Phebus [sup.2] , Elizabeth Ingulli [sup.1] Author Affiliations: (1) grid.266100.3, 0000 0001 2107 4242, Department of Pediatrics, Division of Pediatric Nephrology, Rady Children's Hospital, [...], Background Additional "booster" doses of mRNA SARS-CoV-2 vaccines have become standard of care for immunosuppressed patients, including kidney transplant recipients (KTR). While these additional doses have been shown to be efficacious in the adult KTR population, there is paucity of data for pediatric and adolescent KTR. Methods We conducted a retrospective single-center observational study to determine the proportion of pediatric and adolescent KTR who seroconverted following two- and three-dose regimens of an mRNA SARS-CoV-2 vaccine series. Results Forty-three pediatric and adolescent KTR at our center received at least two doses of an mRNA SARS-CoV-2 vaccine. Seroconversion was noted in 56% of those who received a 2-dose series and increased to 85% in those who received a third dose. In the 16 patients who did not seroconvert after a two-dose series, 12 (75%) seroconverted following the third dose. No serious adverse effects of immunization were noted. Conclusions Our results demonstrate that additional SARS-CoV-2 vaccine doses are not only safe and efficacious in pediatric and adolescent KTR, but may be necessary to optimize antibody response. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information