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Antibodies against aquaporin-4 (AQP4) are specific and pathogenetic for Neuromyelitis Optica (NMO). In a previous study, three linear intracellular AQP4 B-cell epitopes were uncovered in NMO patients. A particular epitope showed high-sequence similarity with a segment of the human TAX1BP1 protein, which is necessary for the replication of HTLV-1 virus. The aim of the present study was to investigate whether immunization of mice with the TAX1BP1 peptide could produce specific antibodies against AQP4 epitopes or induce symptoms. Eight C57Bl/6 mice were immunized with TAX1BP1pep in Complete Freund’s Adjuvant and eight with adjuvant only. Animals received three subcutaneous injections and sera were obtained before each immunization and at sacrifice. All sera were evaluated by ELISA for antibodies against the TAX1BP1peptide, the homologous AQP4 peptide and all linear AQP4 epitopes. Homologous and cross-inhibition assays were performed to ensure binding specificity, and reactivity against conformational AQP4 epitopes was evaluated by a cell-based assay. Sera from immunized animals showed high reactivity against the immunization peptide, and the homologous AQP4 epitope. Inhibition assays confirmed binding specificity. No antibodies were produced against any other epitopes, either linear or conformational. No clinical or brain inflammatory signs were observed in the animals. The induction of antibodies to an AQP4 epitope in mice immunized with the TAX1BP1-derived peptide suggests that a latent HTLV-1 infection could lead to TAX1BP1 antigen presentation and the production of anti-AQP4 antibodies, probably through T cell-mediated mechanisms. Further studies are needed for exploring triggering factors for NMO especially in HTLV-1-endemic regions. [ABSTRACT FROM PUBLISHER]

Background: The prevalence of peripheral neuropathy in patients with Sjögren syndrome remains unclear owing to conflicting results in the published series, with numbers ranging from 2% to over 60% of Sjögren syndrome patients. Whether peripheral neuropathy is a feature of the systemic or glandular disease or whether it is related to a circulating antineuronal antibody remains also uncertain.Methods: The authors reviewed the records of patients with primary Sjögren syndrome (pSS), fulfilling the Revised European-American Classification Criteria, seen in their department from 1992 to 2009. The patients with previously recorded neuropathic features were re-examined clinically and electrophysiologically. Other causes of polyneuropathy were excluded. The authors also searched for circulating antineural antibodies using immunofluorescence and western blot and for antibodies against muscarinic and nicotinic acetylcholine receptors as potential biomarkers.Results: 509 cases met the diagnostic criteria for pSS. Among these, 44 patients were recorded as having neuropathic symptoms. After completing the evaluation, however, only nine (1.8%) had polyneuropathy with objective clinical signs and abnormal electrophysiological findings. The neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The patients with peripheral neuropathy had extraglandular manifestations such as palpable purpura and vasculitis. No evidence of antineural autoimmunity was found, and no candidate biomarkers were identified.Conclusion: Polyneuropathy is a rare manifestation of pSS occurring in 1.8% of patients. In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy of mainly the salivary and lacrimal glands associated with high prevalence of lymphoma. Akt is a phosphoinositide-dependent serine/threonine kinase, controlling numerous pathological processes, including oncogenesis and autoimmunity. Herein, we sought to examine its implication in pSS pathogenesis and related lymphomagenesis. The expression of the entire and activated forms of Akt (partially and fully activated: phosphorylated at threonine-308 (T308) and serine-473 (S473), respectively), and two of its substrates, the proline-rich Akt-substrate of 40 kDa (PRAS40) and FoxO1 transcription factor has been immunohistochemically examined in minor salivary glands (MSG) of pSS patients (n = 29; including 9 with pSS-associated lymphoma) and sicca-complaining controls (sicca-controls; n = 10). The entire and phosphorylated Akt, PRAS40, and FoxO1 molecules were strongly, uniformly expressed in the MSG epithelia and infiltrating mononuclear cells of pSS patients, but not sicca-controls. Morphometric analysis revealed that the staining intensity of the fully activated phospho-Akt-S473 in pSS patients (with or without lymphoma) was significantly higher than sicca-controls. Akt pathway activation was independent from the extent or proximity of infiltrates, as well as other disease features, including lymphoma. Our findings support that the Akt pathway is specifically activated in MSGs of pSS patients, revealing novel therapeutic targets. [ABSTRACT FROM AUTHOR]

To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity. • Modifications in immunosuppressive treatment improve SARS-CoV-2 vaccine immunogenicity. • Seroconversion is compromised by methotrexate, mycophenolate, and rituximab therapy. • Overall disease activity remains stable and vaccination side-effects are mild. [ABSTRACT FROM AUTHOR]

A recent study published in the Journal of Internal Medicine explores the use of IL-1β/DNA complex levels as a diagnostic tool for distinguishing autoinflammatory disorders from autoimmune and infectious diseases. The researchers developed a novel ELISA assay to measure the amount of IL-1β bound to extracellular DNA in plasma samples. They found that circulating IL-1β/DNA complex levels were significantly higher in patients with autoinflammatory disorders compared to those with autoimmune rheumatic diseases, acute infections, and healthy individuals. The assay also showed promise in evaluating treatment response in patients receiving IL-1 inhibitors. Further studies are needed to validate the diagnostic and prognostic utility of this assay in diverse inflammatory disorders. [Extracted from the article]

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren's syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto′s thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens. [ABSTRACT FROM AUTHOR]

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using 'in-house' methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of 'non-responders' a misnomer. [ABSTRACT FROM AUTHOR]

The prevalence of autoantibodies during pregnancy was studied. Sera from 568 women (203 pregnant and 365 non-pregnant) were tested for autoantibodies to double-stranded DNA, car diolipin and extractable cellular antigens. Nineteen out of 203 pregnant women (9.4%) had at least one autoantibody against double-stranded DNA or cardiolipin, mainly of the IgM class. The non-pregnant control group had significantly higher incidence of autoantibodies (17.8%; X2 = 7.39, P < 0.01). Sixty-six out of 568 women had had spontaneous abortions in their past medical history, but there was no correlation between them and the presence of anticardiolipin antibodies. Two of the non-pregnant women had anti-Ro(SSA) antibodies. These findings suggest that (a) the prevalence of autoantibodies decreases during pregnancy; and (b) the presence of anticardiolipin antibodies in healthy pregnant women does not cor relate with any pregnancy-related complications. However, our results indicated that auto immunity is a rather common disorder in healthy women. [ABSTRACT FROM PUBLISHER]

Salivary gland ultrasonography is a promising tool for the evaluation of Sjögren’s syndrome. Cumulative data suggest that ultrasonography is comparable with older imaging modalities such as sialography and scintigraphy. However, certain issues remain to be addressed before it can be integrated into current or future classification systems. [ABSTRACT FROM AUTHOR]