Elevated Antibody Research Articles

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles

BackgroundInhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization.ResultsThe findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains.ConclusionMouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.

Condiciones trombofilicas y su riesgo en una cohorte latinoamericana de gestantes, estudio observacional descriptivo

Objective: To evaluate thrombophilias associated with venous thromboembolism during pregnancy. Methods: Descriptive observational study. Clinical and laboratory alterations were analyzed, as well as the classification of the related profile of a cohort of Latin American pregnant women with thrombotic events during gestation and up to the 120-day puerperium. Antiphospholipid syndrome antibodies, coagulation protein C, S, antithrombin III, mutations against factor V Leiden, mutations in methylenetetrahydrofolate reductase, hyperhomocysteinemia, prothrombin mutation, and elevation of factors VIII, IX, and XI were performed. Results: The mean age was 24,5 + 7,6 years, of which 9 patients (10,3%) had a history of thromboembolism, 23 patients (26,4%) had had at least one fetal loss. Elevated antiphosphatidylserine antibodies were found in 23 patients (26,4%), elevated antibodies against beta2-glycoprotein in 20 patients (22,9%), positive lupus anticoagulant in 16 patients (18,3%), elevated factor VIII in 13 patients (14,94%), elevated factor IX in 15 patients (17,2%), elevated factor XI in 12 patients (13,7%), prothrombin mutation in 7 patients (8,07%) and the others to a lesser extent. Conclusions: The results found here point to the high prevalence rate of underdiagnosed thrombophilic disorders in pregnant women. There is still a lack of strong evidence to analyze this relationship with worse results during pregnancy. Keywords: Coagulation, Thrombosis, Gynecology.

Prevalence and Clinical Associations of Anti-C1q Antibodies in Paediatric Systemic Lupus Erythematosus in Indian Children

Background: Paediatric systemic lupus erythematosus (pSLE) is a heterogeneous, chronic autoimmune disease characterised by multi-system inflammation and the production of antibodies-directed self-antigens. Anti-C1q has been associated with SLE as well as other connective tissue diseases. They have been considered as a marker for disease activity and the presence of nephritis. Objectives: To determine the prevalence of anti-C1q antibodies in the paediatric SLE and to determine clinical associations of elevated anti-C1q antibody levels, especially with lupus nephritis. Methods: All consecutive children with SLE on treatment with immunosuppressive drugs attending our clinic were recruited. After obtaining informed consent, blood samples were tested for anti-C1q antibodies by a commercially available ELISA kit. The prevalence of anti-C1q and its association with lupus nephritis were determined. Results: Out of a total 150 children with SLE, anti-C1q positivity was present in 95 children (64%), at a cut-off value of 20 U/mL. Children with proteinuria, low C3, low C4 and anti-dsDNA positivity had significantly more anti-C1q antibody positivity. Children with lupus nephritis were significantly more likely to have anti-C1q antibody positivity than children without renal involvement (74% vs. 51%, p = .02). Among the children with lupus nephritis, children with active renal disease were more likely to have anti-C1q positivity than in children with quiescent disease (88% vs. 53%, p = .002). Anti-C1q antibodies had a sensitivity of 74% and specificity of 54% at a cut-off value of 22 U/L for renal disease in pSLE. Conclusion: In our study, children with lupus nephritis were significantly associated with elevated anti-C1q antibodies, and children with active renal disease had higher anti-C1q positivity than those with quiescent disease. Anti-C1q levels showed significant associations with low C3, low C4 and anti-dsDNA positivity. Anti-C1q levels did not show significant associations with clinical features of SLE like malar rash, arthritis and CNS involvement. Anti-C1q antibody titres were found to have a positive correlation with renal disease and hence could be used as an adjunctive biomarker in monitoring the disease activity in children with lupus nephritis.

Does parity order or cow antibody level influence the humoral immunity of calves for cattle anaplasmosis?

Anaplasmosis is a widely distributed vector-borne disease of cattle caused by the bacteria Anaplasma marginale, which may lead to severe losses in beef and dairy cattle production. Anecdotal information among farmers suggested that some cows may deliver calves more resilient to anaplasmosis. To investigate this, we tested two hypotheses: (i) whether the parity order or (ii) cow antibody levels may influence the humoral immunity of pre-weaning calves against cattle anaplasmosis. For this study, we sampled 170 cattle (Bos taurus taurus, Angus breed) on a farm in Southern Brazil, comprising 85 cows (50 multiparous and 35 primiparous) and their 85 calves (50days old). Antibodies against A. marginale were investigated using iELISA. Eighty percent of the animals were considered seropositive (100% of the cows and 60% of the calves). There was no significant difference in seroprevalence between calves from primiparous and multiparous cows. However, calves from multiparous cows exhibited higher antibody levels. To address the second question, we classified cows based on their antibody levels to A. marginale (high or low). Calves from cows with high antibody levels also showed elevated antibody levels against A. marginale. Furthermore, calves from cows with high antibody levels had approximately four times greater odds of being seropositive for A. marginale at 50days old than those born to mothers with low antibody levels. In conclusion, the calf's antibody level against A. marginale appears to be related to the cow's parity order and the mother's antibody level.

DOP27 Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's Disease and chronic fatigue syndrome

Abstract Background Patients with Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit elevated antibody responses against gut microbiota flagellins. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) "stimulator" and (2) "silent" flagellins, binding TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 due to a specific C-terminal domain; (3) "evader" flagellins of pathogens, which circumvent TLR5 activation via mutated N-terminal TLR5 binding motifs. Here we studied the characteristics, epitope binding, and sequence (dis)similarity of anti-flagellin antibody responses in CD and ME/CFS. Methods Since conventional antibody profiling methods like enzyme-linked immunosorbent assays [ELISAs] do not allow for large-scale measurements of antibody repertoires, we leveraged phage-display immunoprecipitation sequencing (PhIP-Seq) to characterize 344,000 rationally selected peptide antigens in 256 patients with CD, 40 patients with ME/CFS and in two equally sized groups of age- and sex-matched healthy controls from population-based cohorts in the Netherlands and U.K., respectively. Different sequence alignment strategies were employed to compare flagellin peptide structures with observed antibody-bound flagellin peptide reactivity. Results Both patients with CD and ME/CFS exhibited elevated antibody responses against distinct regions of flagellin peptides compared to healthy individuals (P<0.001). N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling ‘stimulator’ and ‘silent’ flagellins more than evaders. However, C-terminal antibody-bound flagellins showed higher resemblance to stimulator than to silent flagellins in CD, but not in ME/CFS. This group of antibody-bound flagellins was exclusively identified in a subset (10-20%) of patients with CD and characterized by its strong overrepresentation (exceeding 20-fold), underscoring its potential significance in distinguishing pathophysiologic subtypes of CD. Conclusion Antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between diseases. Our results highlight the diagnostic potential of these antibody responses and their impact on innate/adaptive immunity balance.

P193 Fatigued patients with Inflammatory Bowel Disease exhibit distinct systemic antibody epitope repertoires

Abstract Background Patients with inflammatory bowel diseases (IBD) frequently experience fatigue, affecting up to 80% of those with active disease and approximately 50% with quiescent disease. The exact cause of IBD-associated fatigue is often unknown, making clinical management very challenging. In this study we aimed to explore whether patients with quiescent IBD reporting fatigue exhibit specific systemic antibody responses, which could provide insight into immune reactivities underlying fatigue. Methods Systemic antibody epitope repertoires were profiled in 327 patients with IBD (156 Crohn’s disease [CD]; 171 ulcerative colitis [UC]) leveraging phage-display immunoprecipitation sequencing (PhIP-Seq) against 344,000 rationally selected peptide antigens. Fatigue severity was assessed on a 10-point Likert scale, ranging from 1 (no fatigue) to 10 (highest fatigue severity). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] <5 or Simple Clinical Colitis Activity Index [SCCAI] <2.5) and biochemical remission (C-reactive protein [CRP] <5 mg/L) at time of sampling. Multivariable logistic regression analyses, allowing adjustment for potential confounding factors e.g. age, sex, and smoking, were performed to identify associations between fatigue and systemic antibody responses. Results A total of 105 different antibody-bound peptides were associated with fatigue (nominal P-value<0.05), albeit none passed adjustment for multiple comparisons. Among these antibodies, 50 (47.6%) were found to be less frequent in highly fatigued patients (fourth quartile, Q4), while 55 (52.4%) were identified as more frequent in highly fatigued patients compared to those with low fatigue scores (first quartile, Q1). Among highly fatigued patients, antibody responses were primarily directed towards viral antigens, notably several antigens from Epstein-Barr virus (EBV), as well as bacterial antigens, including functional proteins from Streptococcus and Staphylococcus species. Fatigued patients with CD exhibited elevated systemic antibody responses against allergens, Staphylococcus, Pseudomonas aeruginosa, and Shigella spp. Fatigued patients with UC showed higher frequencies of antibody responses against herpes simplex virus (HSV), influenza viruses, and few responses against allergens and Streptococcus bacteria. These results remained materially unchanged when repeating analyses in patients with quiescent IBD. Conclusion This study may suggest a potential role of viral antigens, particularly EBV, in the pathophysiology of fatigue in patients with IBD. However, larger confirmatory studies are needed to validate these findings. PhIP-Seq may represent a valuable strategy to approach the investigation of immune responses underlying complex symptoms such as fatigue.

DOP20 Changes in systemic antibody epitope repertoires from preclinical to established Inflammatory Bowel Disease

Abstract Background Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibit unique immunological changes early in development. Although >300 IBD-specific antibody responses have been identified1, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers. Methods This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq). Results A total of 178 individuals with new-onset IBD were identified (Fig. 1). Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals reported newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR<0.05) pre-diagnosis vs. post-diagnosis (Fig. 2), 14 of which (24%) were previously reported as IBD-specific1. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Those developing UC exhibited 33 differentially abundant antibody responses, while those with CD exhibiting only four (FDR<0.05). Individuals developing IBD exhibited lower frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and varicella-zoster virus, alongside higher antibody responses against bacterial flagellins. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis. Conclusion Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis. 1. Bourgonje et al. Immunity. 2023.

A rare case of anti-DPPX encephalitis combined with neuroleptospirosis

BackgroundNeuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF).Case presentationA previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy.ConclusionWe highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.

Immune characteristics of kidney transplant recipients with acute respiratory distress syndrome induced by COVID-19 at single-cell resolution

BackgroundCOVID-19-induced acute respiratory distress syndrome (ARDS) can result in tissue damage and multiple organ dysfunction, especially in kidney transplant recipients (KTRs) receiving immunosuppressive drugs. Presently, single-cell research on COVID-19-induced ARDS is considerably advanced, yet knowledge about ARDS in KTRs is still constrained.MethodsSingle-cell RNA sequencing (scRNA-seq) analysis was performed to construct a comprehensive single-cell immune landscape of the peripheral blood mononuclear cells (PBMCs) of eight patients with COVID-19-induced ARDS, five KTRs with COVID-19-induced ARDS, and five healthy individuals. Subsequently, we conducted a comprehensive bioinformatics analysis, including cell clustering, enrichment analysis, trajectory analysis, gene regulatory network analysis, and cell–cell interaction analysis, to investigate the heterogeneity of the immune microenvironment in KTRs with ARDS.ResultOur study revealed that KTRs exhibit significant heterogeneity with COVID-19-induced ARDS compared with those of other individuals, with significant reductions in T cells, as well as an abnormal proliferation of B cells and monocytes. In the context of dual influences from immunosuppression and viral infection, KTRs exhibited more specific plasma cells, along with significant enrichment of dysfunctional GZMB and XAF1 double-positive effector T cells and IFI27-positive monocytes. Additionally, robust communication existed among T cells and monocytes in cytokine signaling. These effects impede the process of immune reconstitution in KTR patients.ConclusionOur findings suggest that KTRs with COVID-19-induced ARDS show elevated antibody levels, impaired T cell differentiation, and dysregulation of innate immunity. In summary, this study provides a theoretical foundation for a comprehensive understanding of COVID-19-induced ARDS in KTRs.

Immune system perturbations in patients with long COVID

Klein et al. report multimodal analyses of immune cells, proteins, and physiological parameters in patients with long COVID (LC). At the group level, LC subjects exhibited elevated antibody responses to SARS-CoV-2, but also to herpes viruses, pointing to a general suppression of viral control mechanisms in LC.

P10 New rash in a child of skin of colour

Abstract A 7 year old Nigerian girl was referred by Haematology to the Paediatric Dermatology team with “suspected eczema”. She had known sickle cell disease, for which she was on hydroxycarbamide, Mum reported an 8 month history of a new rash with no systemic features. She had marked indurated plaques on face, forehead and forearms which were associated with scarring and hyperpigmentation. She had a number of investigation including negative urine dipstick. ANA was positive with elevated RO and RNP antibodies. Inflammatory markers were normal. Skin biopsy results were consistent with discoid lupus erythematosus. Stringent photo protection and sun blocking creams were advised. She was commenced on potent topical steroids and hydroxychloroquine which is first line systemic treatment. Within 4 weeks of commencing hydroxychloroquine there was significant flattening of the plaques. She was referred to Paediatric Rheumatology for assessment, given her high risk features. Clinical features of DLE in children are similar to adult DLE in presentation and chronic course. However it is rare in children with less than 2% of patients developing DLE before 10 years of age. DLE tends to be more common and severe in skin of colour. There are complications of scarring and pigmentation. It is important to be aware of the psychological impact on both parent and child’s quality of life. There is high risk of transition to SLE in children with DLE and hence screening bloods and early referral to Rheumatology should be considered.

COVID-19-Associated Neurological Complications in Children.

Neurological manifestations of Severe Acute Respiratory Syndrome coronavirus-2 have been well documented in adults during and after infection with the virus as well as after vaccination. The incidence of severe neurological symptoms among children is very low. This study aimed to analyze the varied neurological manifestations after COVID-19 infection among children and give a report on a single-center experience with these severe neurological symptoms. Case records of patients less than 18 years admitted between July 2021 to December 2022 with neurological manifestations and COVID-19 infection or with elevated COVID-19 antibodies after exclusion of other etiological diagnosis were analyzed. There were 10 cases in the age range of 1-15 years. All the cases had elevated COVID-19 antibodies with history of contact 2-3 weeks prior except one who was positive for COVID-19 infection. Two cases presented with acute ascending paralysis suggestive of Guillain-Barre syndrome. Four cases presented with features of encephalopathy with clinical presentation fulfilling the criteria of Multisystem inflammatory syndrome in children. One case presented with fever and focal seizures with MRI showing sagittal sinus thrombosis, and one presented with fever and altered sensorium with MRI showing leukoencephalopathy. One child had cerebral mucormycosis without any evidence of immunosuppression. There was one child with features of encephalopathy with active COVID-19 infection. The varied presentation highlights the central and peripheral nervous system involvement by the virus in the pediatric population. It also emphasizes the need to investigate for COVID-19 in children presenting with these complaints during the pandemic.

Гормональные, биохимические показатели и уровни микроэлементов крови у молодых женщин с субклиническим гипотиреозом в сочетании с носительством антител к тиреопероксидазе

Many studies have been devoted to investigating the relationship between subclinical hypothyroidism (SH), thyroid gland (TG) autoimmunity, and blood trace elements; however, the data presented in these studies are often contradictory. Aim of study. To identify the factors associated with SH in combination with the presence of Anti-thyroid peroxidase antibody (TPO-Ab). Design. Single-center, observational, single-cohort, cross-sectional, and uncontrolled study. Materials and Methods. This study analyzed 859 women aged 18–45 with SH and without TG dysfunction. Based on thyroid function and TPO-Ab status (presence (+) or absence (–)), four study groups were formed: Group 1 — Euthyroidism and TPO-Ab(–) (n = 503); Group 2 — Euthyroidism and TPO-Ab(+) (n = 164); Group 3 — SH and TPO-Ab(–) (n = 128); Group 4 — SH and TPO-Ab(+) (n = 64). Determination of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPO-Ab levels in serum was provided by enzyme immunoassay on the Evolis Robotized System using the test systems "Thyroid-ELISA-TSH, 0.23–3.4 µIU/ml", "Thyroid-ELISA FT4, 10–23.2 pmol/l", and "Thyroid ELISA-TPO-Ab < 30 U/ml". The reference values were taken from the instructions of the manufacturer Alkor Bio Group (Russia). Measurement of element concentrations was conducted on the atomic absorption spectrometer "МГА-915МД" from Lumex (Russia). Logistic regression analysis with a series of univariate and multivariate models was performed to determine independent predictors of the likelihood of SH and TPO-Ab positive status (relative to euthyroid and TPO-Ab negative individuals). Results. In young women, a decrease in FT4 is associated with increasing age, elevated levels of TSH, TPO-Ab, mercury, decreased heart rate, and reduced levels of thyroglobulin, alkaline phosphatase (ALP), manganese, nickel, selenium, lead, and the triglyceride/glucose index. An increase in TSH is associated with lower levels of ALP, manganese, and nickel, and higher mercury levels. The likelihood of having SH combined with the presence of TPO-Ab, compared to the group without thyroid dysfunction and elevated antibodies, increases with reduced concentrations of iodine (odds ratio (OR) = 0.739; 95% confidence interval (CI): 0.618–0.884, p = 0.001), selenium (OR = 0.987; 95% CI: 0.976–0.998, p = 0.018), and zinc (OR = 0.998; 95% CI: 0.997–0.999, p = 0.023), and with elevated lead levels (OR = 1.106; 95% CI: 1.006–1.217, p = 0.038). In a multivariate regression model, the probability also increases with decreased iodine and cadmium levels, and elevated lead levels. Conclusion. Reduced concentrations of iodine, selenium, and zinc, along with elevated blood lead levels, are factors associated with the activation of thyroid autoimmunity and the presence of SH in combination with elevated TPO-Ab levels. Keywords: thyroid gland, thyroid function hormones, microelements, thyroid peroxidase antibodies, young age, women.

High prevalence of long COVID in anti-TPO positive euthyroid individuals with strongly elevated SARS-CoV-2-specific T cell responses and moderately raised anti-spike IgG levels 23 months post-infection.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), causes post-acute infection syndrome in a surprisingly large number of cases worldwide. This condition, also known as long COVID or post-acute sequelae of COVID-19, is characterized by extremely complex symptoms and pathology. There is a growing consensus that this condition is a consequence of virus-induced immune activation and the inflammatory cascade, with its prolonged duration caused by a persistent virus reservoir. In this cross-sectional study, we analyzed the SARS-CoV-2-specific T cell response against the spike, nucleocapsid, and membrane proteins, as well as the levels of spike-specific IgG antibodies in 51 healthcare workers, categorized into long COVID or convalescent control groups based on the presence or absence of post-acute symptoms. Additionally, we compared the levels of autoantibodies previously identified during acute or critical COVID-19, including anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-neutrophil cytoplasmic antibodies, and anti-thyroid peroxidase (anti-TPO). Furthermore, we analyzed the antibody levels targeting six nuclear antigens within the ENA-6 S panel, as positivity for certain anti-nuclear antibodies has recently been shown to associate not only with acute COVID-19 but also with long COVID. Finally, we examined the frequency of diabetes in both groups. Our investigations were conducted at an average of 18.2 months (convalescent control group) and 23.1 months (long COVID group) after confirmed acute COVID-19 infection, and an average of 21 months after booster vaccination. Our results showed significant differences between the two groups regarding the occurrence of acute infection relative to administering the individual vaccine doses, the frequency of acute symptoms, and the T cell response against all structural SARS-CoV-2 proteins. A statistical association was observed between the incidence of long COVID symptoms and highly elevated anti-TPO antibodies based on Pearson's chi-squared test. Although patients with long COVID showed moderately elevated anti-SARS-CoV-2 spike IgG serum antibody levels compared to control participants, and further differences were found regarding the positivity for anti-nuclear antibodies, anti-dsDNA, and HbA1c levels between the two groups, these differences were not statistically significant. This study highlights the need for close monitoring of long COVID development in patients with elevated anti-TPO titers, which can be indicated by strongly elevated SARS-CoV-2-specific T cell response and moderately raised anti-spike IgG levels even long after the acute infection. However, our results do not exclude the possibility of new-onset thyroid autoimmunity after COVID-19, and further investigations are required to clarify the etiological link between highly elevated anti-TPO titers and long COVID.

Hashimoto’s Encephalopathy: A Review

The condition "Hashimoto's encephalopathy" (HE) refers to a cerebral dysfunction syndrome with elevated antithyroid peroxidase antibody titers that is thought to have an autoimmune cause. Similar to autoimmune thyroid illness, women are more likely than men to develop HE. It has been documented in adult, geriatric, and pediatric populations worldwide. The clinical appearance may be recurrent and remitting, with myriad symptoms involving myoclonus, seizures, episodes resembling strokes, cognitive deterioration, and neuropsychiatric symptoms. Clinically and biochemically, thyroid function is often normal. Although HE seems to be a rare disorder, it should be taken into consideration when treating "investigation negative encephalopathies" because it responds to corticosteroid treatment. The results of neuroimaging frequently do not help to clarify the diagnosis. High titers of antithyroid antibodies, specifically antithyroid peroxidase antibodies, are diagnosed in the setting of the usual clinical picture. Corticosteroid treatment is nearly always successful, although relapses are common. Other immunomodulatory treatments, like intravenous immunoglobulin and plasma exchange, are often effective as well. Despite a statistical correlation to autoimmune thyroid illness, the cause of HE is not well understood. Research is still needed to fully understand the connections between clinical images, thyroid disease, auto-antibody pattern, and brain pathology. It's possible that over time, a class of nonvasculitic autoimmune inflammatory meningoencephalopathies will include HE. Some writers have proposed severing all connections to Hashimoto and calling the illness, SREAT - "steroid responsive encephalopathy associated with autoimmune thyroiditis".

A case of autoimmune encephalitis in a patient with a solitary intracranial plasmacytoma.

A 65-year-old woman presented with fever and abnormal behavior. Magnetic resonance imaging showed swelling of the left medial temporal lobe and an intracranial extra-axial occipital tumor. While her neurological symptoms improved after the administration of corticosteroid therapy under the suspicion of autoimmune encephalitis, the occipital tumor unexpectedly shrank, and the diagnosis of a solitary plasmacytoma was confirmed by biopsy. Additional examinations revealed elevated anti-glutamate receptor antibodies in the cerebrospinal fluid. The patient was diagnosed with autoimmune encephalitis concurrent with an intracranial solitary plasmacytoma. Central nervous system involvement can be considered a neurological complication in patients with a solitary plasmacytoma.

Effectiveness of Covid-19 Vaccine in Pregnant Women: A Systematic Review

The newly developed COVID-19 vaccine faces public's concerns in terms of its effectiveness and safety as an approach in combating COVID-19 pandemic. It is well-established that COVID-19 vaccine is effective alongside being the most promising approach against COVID-19 infection in both general and vulnerable populations. This study aims to evaluate the effectiveness of COVID-19 vaccine in pregnant women as a subgroup of vulnerable population by analysing several important immunological parameters in pregnant women. Specifically, it investigates how effective the COVID-19 vaccine will reduce the infection rate and how it will affect the mothers' antibody levels against SARS-CoV-2. In this study, the immunological parameters investigated are maternal antibody response against SARS-CoV-2 and the transplacental transfer of the antibody. To test the hypothesis that COVID-19 vaccine is effective in pregnant women, a systematic review was conducted on previous studies regarding COVID-19 vaccine and its outcomes in pregnancy. Results were narratively analysed. The results showed reduced COVID-19 infection rate, elevated maternal antibody titre against SARS-CoV-2 and positive transplacental anti-SARS-CoV-2 IgG antibody transfer in vaccinated pregnant women in comparison to unvaccinated pregnant women. These results suggest that COVID-19 vaccine is highly effective against COVID-19 infection in pregnant women. Furthermore, COVID-19 vaccine not only elicits sufficient maternal antibody response as an immunity for mothers against COVID-19 infection but also provides similar protection for infants via passive immunity by means of transplacental antibody transfer. In conclusion, the uptake of COVID-19 vaccine and future booster dose by pregnant women should be strongly encouraged due to its favourable outcomes and protection against COVID-19 disease.

Evidence of a Sjögren's disease-like phenotype following COVID-19 in mice and humans.

Sjögren's Disease (SjD) is a systemic autoimmune disease characterized by lymphocytic inflammation of the lacrimal and salivary glands (SG), dry eyes and mouth, and systemic symptoms. SARS-CoV-2 may trigger the development or progression of autoimmune diseases. To test this, we used a mouse model of SARS-CoV-2 infection and convalescent patients' blood and SG in order to understand the development of SjD-like autoimmunity after infection. First, SARS-CoV-2-infected human angiotensin-converting enzyme 2 (ACE2) transgenic mice exhibited decreased salivation, elevated antinuclear antibodies (ANA), and lymphocytic infiltration in the lacrimal and SG. The sera from patients with COVID-19 sera showed increased ANA (i.e., anti-SSA [Sjögren's-syndrome-related antigen A]/anti-Ro52 and anti-SSB [SS-antigen B]/anti-La). Male patients showed elevated anti-SSA compared with female patients, and female patients exhibited diverse ANA patterns. SG biopsies from convalescent COVID-19 patients were microscopically similar to SjD SG with focal lymphocytic infiltrates in 4 of 6 patients and 2 of 6 patients exhibiting focus scores of at least 2. Lastly, monoclonal antibodies produced in recovered patients blocked ACE2/spike interaction and cross-reacted with nuclear antigens. Our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD-affected SGs were histologically indistinguishable from convalescent COVID-19 patients. The results implicate that SARS-CoV-2 could be an environmental trigger for SjD.

An overview of periodontal disease in pregnancy

Periodontal disease (PD), an inflammatory and infectious condition affecting the tissues supporting teeth, is prevalent among pregnant women due to hormonal changes. Studies indicate a link between PD and adverse pregnancy outcomes, including preterm labor and low birthweight newborns, likely due to increased inflammatory mediators. Oral pathogens like Tannerella forsythia and Porphyromonas gingivalis have been associated with these complications. The most prevalent oral conditions affecting pregnant women that may influence the course of their pregnancy are periodontitis, gingivitis, and dental caries. From supragingival plaques to subgingival infections and PD, these conditions are linked to one another. Elevated maternal serum antibodies to these pathogens and inflammatory markers correlate with poor pregnancy outcomes. Animal models further support the connection between PD and fetal health issues. While research suggests that periodontal treatment may reduce the risk, the exact mechanisms remain complex and multifactorial. Integrating dental care into prenatal care is vital for prevention and management.

Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus

Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1⍺, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity.