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Introduction: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB. Clinical findings: We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision. Diagnosis: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients. Conclusion: NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella. [ABSTRACT FROM AUTHOR]

Abstract Introduction Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB. Clinical findings We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision. Diagnosis MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients. Conclusion NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella.

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Background Methods Results Conclusion This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database.Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear.This was a population‐based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non‐RA control was obtained by age and sex‐matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD‐10) code M05, prescription of disease‐modifying anti‐rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD‐10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD‐10 code of migraine (G43).A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow‐up of 4.4 years after a 1‐year lag period. Patients with RA had a 1.2‐fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17–1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15–1.24 in SPRA; aHR 1.26, CI 1.19–1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88–1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05).RA was linked to a higher migraine risk, regardless of seropositivity. [ABSTRACT FROM AUTHOR]

Introduction: Eculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting. Methods: We collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative). Results: Both treatments showed similar efficacy relative to the MG-ADL scale reduction (p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- (p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset (p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod (– 16.7 vs – 5.2 mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was – 13.1 mg of the daily dose for each month of follow-up for eculizumab-treated patients and – 3.2 for efgartigimod (p = 0.001). We found three serious events, all not related to treatment in the investigator's opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment. Conclusions: Our study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients. [ABSTRACT FROM AUTHOR]

Emerging evidence shows increased humoral response post‐omicron surge, but research on T cell responses is limited. This study investigated the durability, magnitude, and breadth of SARS‐CoV‐2‐spike‐specific T cell responses in 216 two‐dose vaccinated individuals pre‐ and post‐omicron surge. Post‐surge samples showed enhanced T cell responses, indicating widespread asymptomatic exposure to omicron. Further analysis of 105 individuals with multiple exposures to SARS‐CoV‐2 through boosters or infections showed that post‐omicron, two‐dose vaccinated individuals had T cell responses comparable to those of COVID‐19 convalescents or boosted individuals. Additionally, we report cross‐reactive T cell responses against omicron sub‐variants, including BA2.86, remained strong, with preserved frequencies of spike‐specific stem‐cell‐like memory T cells. In silico prediction indicates that mutated epitopes of JN.1 and KP.2 retain over 95.6% of their HLA binding capability. Overall, our data suggests that T cell responses are sustained, enhanced, and cross‐reactive against emerging SARS‐CoV‐2 variants following symptomatic or asymptomatic omicron infection. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. Objective: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. Methods: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). Results: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG– MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. Conclusions: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and—just like H+L- and Fcγ-specific testing—might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted. [ABSTRACT FROM AUTHOR]

Anti‐Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep‐2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti‐Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti‐Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High‐titre results (1 ≥ 1/320) were more common in patients with AID. Anti‐Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)‐positive patients, making it a remarkable finding. The majority of individuals with high‐titre anti‐Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti‐cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor (RF). Finally, high‐titre anti‐Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the clinical and immune characteristics of patients with primary Sjögren’s syndrome (pSS) who were negative for anti–Sjögren’s-syndrome-related antigen A antibodies (anti-SSA) and anti–Sjögren’s-syndrome-related antigen B antibodies (anti-SSB) in Chinese population. Methods A retrospective study were performed and 232 patients with pSS were analyzed. Patients positive for anti-SSA or/and anti-SSB were termed as seropositive pSS, and these negative for both anti-SSA and anti-SSB (non-antinuclear antibodies) as seronegative pSS. Clinical manifestations and laboratory findings were compared between the two groups. Results Among the 232 patients with pSS, 192 (82.8%) were seropositive pSS and 40 (17.2%) were seronegative pSS. Compared to seropositive pSS, seronegative pSS were older and with higher percentage of low disease activity (ESSDAI

Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both p < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2‐glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine‐prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2‐glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin‐cardiolipin complex, anti‐protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work‐out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified. [ABSTRACT FROM AUTHOR]

Objectives Autoantibody-negative RA differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. Methods Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular PsA and 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B cell chemoattractant CXCL13 were compared among groups. Results Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [ s. d.] 1.8 [1] vs 2.4 [0.6], P  = 0.03, and 38.2% vs 62.9%, P  = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. Conclusions The synovial and serum immunophenotype indicative of B lymphocyte involvement in autoantibody-negative RA differs from that of autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies. Aims: To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies. Methods: We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded. Results: Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18–39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40–59, 6% vs. 29%; p = 0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%). Conclusion: Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed. [ABSTRACT FROM AUTHOR]

Objective: The underlying pathology of autoimmune encephalitis is not well characterized due to the limited opportunities to study tissue specimens. Autopsy specimens available at prion surveillance centers from patients with suspected Creutzfeldt-Jakob disease offer a unique opportunity to study the pathology of autoimmune encephalitis. Our objective was to describe pathological findings of autoimmune encephalitis specimens submitted to the U.S. National Prion Disease Pathology Surveillance Center. Methods: Pathology reports were obtained from the National Prion Center. Specimens negative for prion disease were screened for inflammatory pathology and those suggestive of autoimmune encephalitis were analyzed. Cases identified on autopsy were compared to institutional cases with fatal seronegative autoimmune encephalitis and available brain biopsy. Results: Between 1998 and 2022, 7934 specimens were evaluated of which 2998 (38%) were negative for prion protein. Querying the database for alternative diagnoses of encephalitis/encephalopathy yielded 43 cases that were screened by an experienced neuropathologist yielding 14 (0.5%) cases consistent with autoimmune encephalitis. Most specimens showed diffuse inflammation involving the limbic system (86%), basal ganglia (86%), cortex (71%), diencephalon (71%), and in some cases the brainstem (43%) and cerebellum (43%). Lymphocytic inflammatory infiltrate was predominantly perivascular with parenchymal extension in 64%. Microglial activation/nodules were seen in 64% of cases. Neuronal loss was present only in 50%. Pathological findings were identical to biopsy specimens from our institutional cohort. Discussion: Seronegative AE may have consistent pathology with diffuse or multifocal perivascular inflammation and microglial activation. Half the patients do not have neuronal loss suggesting a potential for neurological recovery. These findings are preliminary and require further confirmation. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively. Case presentation: We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab. Conclusion: Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive. [ABSTRACT FROM AUTHOR]

Objective: Emerging evidence shows that patients with myasthenia gravis (MG) were at a higher risk for the co-occurrence of other autoimmune diseases, which reflects phenotypic heterogeneity in MG. The coexistence of MG and cryptogenic organizing pneumonia (COP) has rarely been reported. The present case is to report the coexistence of triple-seronegative MG and pathology-proven COP in a patient. Methods: The clinical data of the patient were derived from medical records of Nanjing First Hospital, Nanjing Medical University, China. Written informed consent was obtained from the patient. Results: We presented a 56-year-old man with acute respiratory syndrome, who was diagnosed with COP based on the intra-alveolar fibroinflammatory buds (Masson's bodies) in the pathology of bronchoscopy biopsy. Oral prednisone induced dramatic symptomatic improvement and complete resolution of previous lung lesions. After a stable course of no respiratory symptom for 2 months, he was referred to the neurology department with complaints of fluctuating generalized muscle weakness. He was diagnosed with triple-seronegative MG based on fluctuating weakness, neostigmine test-positivity and RNS-positivity. After three-month treatment with pyridostigmine in combination with tacrolimus, the symptoms gradually improved and he achieved minimal symptom expression. Conclusions: This case highlights the rare coexistence of triple-seronegative MG and pathology-proven COP. However, a causal association between COP and MG cannot be explicitly ascertained. In future, more data are needed to clarify the relationship, taking into account the limited number of cases reported with this coexistence of the diseases. [ABSTRACT FROM AUTHOR]

Background: Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. Methods: We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity. Results: Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11–1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12–2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24–1.60). Conclusions: In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA. [ABSTRACT FROM AUTHOR]

Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both p < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection.

Introduction: Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]). Methods: Sarilumab initiators from the ACR-RISE Registry, with ≥ 1 prescription on/after its FDA approval (2017–2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase 3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and Cohort C (characteristics matched to the phase 3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12 months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3 mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24 weeks. Results: Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12 months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5 mg/l) showed better response to sarilumab in rule-positive patients. Conclusions: In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data. Plain Language Summary: Rheumatoid arthritis (RA) is a condition that may cause joint damage, if untreated. Sarilumab is an advanced medication, approved for treating moderate-to-severe RA in patients not responding to initial standard medicines. Clinical trials have shown that sarilumab improves RA symptoms; however, some people do not respond. This is a common problem in RA treatment. Physicians measure proteins in people's blood (called biomarkers; e.g., anticyclic citrullinated peptide antibodies [ACPA], C-reactive protein [CRP], and rheumatoid factor [RF]) to predict a medicine's response. A previous study showed that people with positive blood tests for ACPA and CRP (> 12.3 mg/l) responded well to sarilumab; this study was based on machine learning (a branch of science using computers) and identified factors that could be linked to treatment benefits. The present study analyzed routine data of 2949 people from the ACR-RISE Registry and showed an improvement in RA symptoms after 6 and 12 months of sarilumab, with a greater improvement noted in patients previously treated with other medicines. Biomarkers were tested in 205 people to check whether they could predict treatment response in day-to-day life. People were called rule-positive if they tested positive for RF and/or ACPA with CRP > 12.3 mg/l, and otherwise rule-negative. After 24 weeks of treatment, rule-positive people had a greater chance of disease improvement than rule-negative people. These results showed the benefits of sarilumab in RA in routine care and suggested the usefulness of machine learning in identifying biomarkers that physicians can use to make treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Given the catastrophic results of antiphospholipid syndrome (APS) left untreated, the possible role of non-criteria antiphospholipid (aPL) in the diagnosis of seronegative (SN)-APS patients, and its impact on the timely treatment of people with SNAPS, the present review aimed to gather the available literature up to 2022 focusing on the role of non-criteria aPL in the diagnosis of SN cases suspected of APS using non-criteria aPL. Methods: All published papers focusing mainly on the diagnosis of the SN-APS patients by non-criteria aPL were searched in four databases of PubMed, Scopus, Medline, and Web of Sciences, followed by manual search up to 20 February 2022 using such keywords as "Antiphospholipid Syndrome", "Seronegative", and "Non-Criteria". Finally, 15 studies were selected after the detailed evaluation of the full-text versions. Results: Based on the obtained results of our study, 24% to 81.9% of the SN-APS cases were positive for at least one isotype of non-criteria aPL. Thrombophilia events were more frequent in the APS population, compared to SN-APS; however, obstetric manifestations were more frequent in the SN-APS population, compared to seropositive-APS. Antivimentin/cardiolipin and antiphosphatidylserine/prothrombin IgG/IgM were introduced as the best non-criteria aPL to detect seronegative cases that were correlated with clinical manifestations. Conclusion: It seems that a combination of testing for non-criteria aPL should be performed for cases suspected of APS with negative criteria markers. [ABSTRACT FROM AUTHOR]

Objective: To assess the demographics, neurologic manifestations, comorbidities, and treatment of patients with seronegative primary Sjögren's syndrome (pSS). Patients and methods: We conducted a retrospective chart review on patients with seronegative pSS evaluated by a neurologist at the University of Utah Health between January 2010 and October 2018. The diagnosis was based on characteristic symptoms, positive minor salivary gland biopsy according to the American-European Consensus Group 2002 criteria, and seronegative antibody status. Results: Of 45 patients who met the study criteria, 42 (93.3%) were Caucasian, and 38 (84.4%) were female. The patients' mean age at diagnosis was 47.8 ± 12.6 (range 13-71) years. Paresthesia, numbness and dizziness, and headache were noted in 40 (88.9%), 39 (86.7%), and 36 patients (80.0%), respectively. Thirtyfour patients underwent brain magnetic resonance imaging. Of these, 18 (52.9%) showed scattered nonspecific periventricular and subcortical cerebral white matter T2/fluid-attenuated inversion recovery hyperintense foci. Twenty-nine patients (64.4%) presented to the neurology clinic prior to pSS diagnosis, and the median delay in diagnosis from the first neurology clinic visit was 5 (interquartile ranges 2.0-20.5) months. Migraine and depression were the most common comorbidities in 31 patients (68.9%). Thirty-six patients received at least one immunotherapy, and 39 were on at least one medication for neuropathic pain. Conclusion: Patients often display various nonspecific neurological symptoms. Clinicians should express a high degree of skepticism regarding seronegative pSS and consider minor salivary gland biopsy to avoid delaying diagnosis, as undertreatment can affect patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis (AE) might be seropositive or seronegative, depending on whether antibodies targeting well-characterized neuronal antigens can be detected or not. Since data on treatment efficacy in seronegative cases, are scarce, the main rationale of this study was to evaluate immunotherapy response in seronegative AE in comparison to seropositive cases. Methods: An electronic database search retrospectively identified 150 AE patients, treated in our tertiary care university hospital between 2010 and 2020 with an AE. Therapy response was measured using both general impression and the modified Rankin Scale (mRS). Results: Seventy-four AE patients (49.3%) were seronegative and 76 (50.7%) seropositive. These cases were followed up for a mean of 15.3 (standard deviation, SD, 24.9) and 24.3 months (SD 28.1), respectively. Both groups were largely similar on the basis of numerous clinical and paraclinical findings including cerebrospinal fluid, electroencephalography, magnetic resonance imaging, and 18-F-fluor-desoxy-glucose-positron-emmission-tomography pathologies. The majority of patients (80.4%) received at least one immunotherapy, which were glucocorticoids in most cases (76.4%). Therapy response on general impression was high with 49 (92.5%) of treated seronegative, and 57 (86.4%) of treated seropositive AE cases showing improvement following immunotherapies and not significantly different between both groups. Notably, the proportion of patients with a favorable neurological deficit (mRS 0-2) was twice as high during long-term follow-up as compared to baseline in both groups. Conclusion: Since both, patients with seronegative and seropositive AE, substantially benefitted from immunotherapies, these should be considered in AE patients irrespective of their antibody results. [ABSTRACT FROM AUTHOR]

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals. [ABSTRACT FROM AUTHOR]

Background: RS3PE (remitting seronegative symmetrical synovitis with edema and pitting) is a rare entity of unknown etiology that has been related to genetic predisposition due to the presence of HLA-A2 in 50% of cases and less frequently HLA-B7. Its pathogenesis is unknown, but it has been related to growth factors, and some mediators (TNF, IL-6). It is common in elderly people and the course of this illness presents with acute symmetrical polyarthritis, accompanied by edema in hands and feet. The diagnosis requires a high index of suspicion and to differentiate it from other entities such as rheumatoid arthritis, complex regional pain syndrome, rheumatic polymyalgia, in addition to ruling out malignant neoplasms, since there are many reports of its association with both solid and hematological neoplasms, being of bad prognosis when there is association. When there is no association with cancer, it responds well to the use of low doses of steroids and its prognosis is usually favorable. Clinical case: 80-year-old woman with an acute onset with polyarthralgia, functional limitation associated with pitting edema in hands and feet. After approaching the patient and ruling out associated neoplasms, it was diagnosed RS3PE. It was managed with prednisone, observing a good response, with remission of the manifestations at 6 weeks and subsequent suspension of the steroid. Conclusions: RS3PE is a rare entity, and a high index of suspicion is required for the diagnosis. A complete approach is important to rule out cancer in patients affected with this syndrome. Prednisone continues to be the best therapeutic option. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

Opportunistic infections (OIs) are a significant cause of morbidity and mortality in immunosuppressed patients and may be due to bacteria, virus, protozoa, or fungi. Toxoplasmosis is a common cause of central nervous system infection in human immunodeficiency virus (HIV) patients. Coccidioidomycosis is a relatively common fungal infection that may lead to disseminated disease and fungemia in immune-compromised hosts living in endemic regions. This single-patient case report documents the presentation, diagnosis, management, and outcome of concomitant central nervous system toxoplasmosis and diffuse miliary pneumonia with fungemia due to disseminated seronegative Coccidioides immitis in a 33-year-old male patient recently diagnosed with chronic advanced HIV. Impaired cellular immune function, such as defects in the IL-12/IFN-γ pathway or T-helper IL-17-mediated response, is associated with increased severity of coccidioidomycosis. Fungemia and acute respiratory distress syndrome are both associated with very high mortality in coccidioidomycosis. In HIV hosts, negative Coccidioides serology can be seen in up to 25% of cases and therefore other diagnostic modalities should be initiated promptly and simultaneously. This case demonstrates simultaneous OI in the setting of advanced acquired immune deficiency syndrome and emphasizes the need for early diagnosis of HIV and OI in order to ensure prompt initiation of antiretroviral therapy, prophylactic, and therapeutic medications.

Background: Limbic encephalitis (LE) is a rare variant of autoimmune encephalitis. It often manifests with subacute neuropsychiatric symptoms of agitation, delusions, variable seizure semiology, and short-term memory loss. Seronegative limbic encephalitis can pose a diagnostic conundrum owing to its inadequately understood pathophysiology. Case presentation: We report a rare case of a young male with subacute neuropsychiatric manifestations of delusions, agitations and seizures. He was diagnosed with seronegative limbic encephalitis (SNLE). Brain MRI demonstrated bilateral Claustrum sparing sign. An EEG showed continuous left-sided epileptiform discharges in periodic to predominantly left middle temporal. Patient condition gradually improved with pulsed methylprednisolone, intravenous immunoglobulins and anti-seizure medications. Conclusion: Claustrum remains one of the least understood neuroanatomical structures. Claustrum sign has been reported in febrile infection-related epilepsy syndrome (FIRES), LE, and autoimmune refractory epilepsy. To the best of our knowledge, we report the first case in literature with Claustrum sparing sign in seronegative Limbic Encephalitis. Further experimental models and researches are warranted to better understand the unique function of the claustrum and unravel possible other attributable auto-antibodies, which could alter treatment and prognosis.

BackgroundAutoimmune encephalitis (AE) might be seropositive or seronegative, depending on whether antibodies targeting well-characterized neuronal antigens can be detected or not. Since data on treatment efficacy in seronegative cases, are scarce, the main rationale of this study was to evaluate immunotherapy response in seronegative AE in comparison to seropositive cases.MethodsAn electronic database search retrospectively identified 150 AE patients, treated in our tertiary care university hospital between 2010 and 2020 with an AE. Therapy response was measured using both general impression and the modified Rankin Scale (mRS).ResultsSeventy-four AE patients (49.3%) were seronegative and 76 (50.7%) seropositive. These cases were followed up for a mean of 15.3 (standard deviation, SD, 24.9) and 24.3 months (SD 28.1), respectively. Both groups were largely similar on the basis of numerous clinical and paraclinical findings including cerebrospinal fluid, electroencephalography, magnetic resonance imaging, and 18-F-fluor-desoxy-glucose-positron-emmission-tomography pathologies. The majority of patients (80.4%) received at least one immunotherapy, which were glucocorticoids in most cases (76.4%). Therapy response on general impression was high with 49 (92.5%) of treated seronegative, and 57 (86.4%) of treated seropositive AE cases showing improvement following immunotherapies and not significantly different between both groups. Notably, the proportion of patients with a favorable neurological deficit (mRS 0-2) was twice as high during long-term follow-up as compared to baseline in both groups.ConclusionSince both, patients with seronegative and seropositive AE, substantially benefitted from immunotherapies, these should be considered in AE patients irrespective of their antibody results.

We report a 34-year-old man who presented to us with mildly pruritic bilaterally symmetrical brownish plaques over the dorsum of both hands and feet for 2 months, whose dermatological and histopathological findings were in accordance with necrolytic acral erythema, but the serologic marker for hepatitis C virus was negative. He showed irrefutable clinical improvement with oral zinc therapy. Very few cases of necrolytic acral erythema without the presence of HCV infection has been reported, which led to this report.

• Most myasthenic mimics had never undergone thorough neurophysiologic assessment. • Mimics often received inappropriate and harmful therapy for years. • Functional neurological disorder was common. • Suspect mimics in static and refractory disease. • Diagnosing mimics is important to wean therapies. Myasthenia gravis often presents a diagnostic challenge and may be misdiagnosed, particularly in seronegative disease with active symptoms. We retrospectively evaluated 61 patients following the introduction of single fibre electromyography at our service, and identified 8 mimics which had been inappropriately diagnosed and treated as refractory myasthenia gravis. 6 of these were seronegative, but two had positive acetylcholine receptor (AChR) antibodies. The final diagnoses included one case each of chronic progressive external ophthalmoplegia, chronic ptosis, oculopharyngeal muscular dystrophy, and an undifferentiated disorder suspicious for either a mitochondrial cytopathy or low-grade myositis. Four were diagnosed with functional neurological disorder, one of which had a superimposed thyroid myopathy and orbitopathy. We found the average duration of misdiagnosis was 9 years (SD±5.2, median 11 years), and patients were often exposed to years of unnecessary treatment. All patients had received anticholinesterase therapy, three had immunotherapy, and three surgical interventions were performed including two thymectomies. We found myasthenic mimics should be suspected in disease that is static and treatment refractory, and functional mimics in disease with frequent flares. Thorough neurophysiologic assessment is important, particularly when making a diagnosis of seronegative myasthenia gravis. [ABSTRACT FROM AUTHOR]

Despite the highly infectious nature of the SARS-CoV-2 virus, it is clear that some individuals with potential exposure, or even experimental challenge with the virus, resist developing a detectable infection. While a proportion of seronegative individuals will have completely avoided exposure to the virus, a growing body of evidence suggests a subset of individuals are exposed, but mediate rapid viral clearance before the infection is detected by PCR or seroconversion. This type of "abortive" infection likely represents a dead-end in transmission and precludes the possibility for development of disease. It is, therefore, a desirable outcome on exposure and a setting in which highly effective immunity can be studied. Here, we describe how early sampling of a new pandemic virus using sensitive immunoassays and a novel transcriptomic signature can identify abortive infections. Despite the challenges in identifying abortive infections, we highlight diverse lines of evidence supporting their occurrence. In particular, expansion of virus-specific T cells in seronegative individuals suggests abortive infections occur not only after exposure to SARS-CoV-2, but for other coronaviridae, and diverse viral infections of global health importance (e.g., HIV, HCV, HBV). We discuss unanswered questions related to abortive infection, such as: 'Are we just missing antibodies? Are T cells an epiphenomenon? What is the influence of the dose of viral inoculum?' Finally, we argue for a refinement of the current paradigm that T cells are only involved in clearing established infection; instead, we emphasise the importance of considering their role in terminating early viral replication by studying abortive infections. [ABSTRACT FROM AUTHOR]

Background. Since the beginning of the coronavirus disease (COVID-19) pandemic, numerous infections have been observed with various symptoms and degrees of severity. Not all patients have had a confirmation of infection made using reverse transcription polymerase chain reaction (RT-PCR) or antigen tests. It has been observed that some people, including convalescents or those without knowledge of a past infection, perform serological tests to detect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Objectives. We aimed to evaluate the levels of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies in a cohort of convalescents and in individuals not previously infected, who were willing to get vaccinated. We also aimed to assess several socio-clinical factors associated with participants' humoral responses. Materials and methods. We recruited 298 individuals from the region of Lower Silesia who were willing to get vaccinated for SARS-CoV-2. The participants were divided into 2 groups: convalescents (group I) and participants without a past infection (group II). Several seropositive individuals in group II were identified, and they were transferred to group I, resulting in a final distribution of 171 individuals in group I and 127 individuals in group II. For serological testing, the QuantiVac anti-SARS-CoV-2 (IgG) enzyme-linked immunosorbent assay (ELISA) was used. Results. The results showed the presence of anti-SARS-CoV-2 IgG antibodies in participants from group I, with an average number of 190.3 IU/mL. Twenty-three participants (13.45%) did not have a detectable level of antibodies despite a previous SARS-CoV-2 infection. In 21 participants (12.28%), antibodies were detected despite no previous symptoms of infection (average level: 145.0 IU/mL). Conclusions. Older participants were more likely to experience a symptomatic SARS-CoV-2 infection, and the severity of the symptoms was related to higher antibody titers seen later after COVID-19. Numerous individuals from group II were unaware of past SARS-CoV-2 infections. In several participants, antibodies were not detected despite a previous infection. [ABSTRACT FROM AUTHOR]

Objective: We investigated the factors that affect rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) positivity in patients with rheumatoid arthritis (RA).Methods: The study included all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017. We recorded age at diagnosis, sex, smoking habit, BMI (kg/m2), and family history, and investigated the association between these variables and RF and anti-CCP positivity.Results: We recruited 1685 patients with RA. The mean age at diagnosis was 51.9 years, and 83.4% of the patients were women. Positivity rates of RF and anti-CCP almost linearly decreased along with the increase in age at RA diagnosis (grouped by decade) after ≥ 30 years of age (RF: 80.5%, 84.2%, 81.1%, 78%, 74.6%, 62.6%, 51.4%, P < 0.001; anti-CCP: 79.9%, 87.4%, 81.7%, 74%, 70.5%, 60.2%, 37.1%; P < 0.001). Multivariable analysis revealed that age was independently associated with seronegativity in women (RF: odds ratio [OR] 0.98, 95% CI 0.97-0.99, P < 0.001; anti-CCP: OR 0.97, 95% CI 0.96-0.98; P < 0.001), nonsmoking history (RF: OR 0.98, 95% CI 0.97-0.99, P < 0.001; anti-CCP: OR 0.97, 95% CI 0.96-0.98; P < 0.001), and BMI < 25 (RF: OR 0.98, 95% CI 0.97-0.99; P < 0.001; anti-CCP: OR 0.97, 95% CI 0.97-0.98; P < 0.001).Conclusion: Aging is an independent contributor for seronegative RA in patients who are female, have a nonsmoking history, and a BMI < 25. [ABSTRACT FROM AUTHOR]

• The prevalence of "clustered" AChR- as well as MuSK- and LRP4- autoantibodies in "triple seronegative" myasthenia gravis assessed by a live cell-based assay (L-CBA) was low. • "Clustered" AChR-autoantibodies were identified in only 4.5% of patients, while none of the patients were positive for MuSK- or LRP4 autoantibodies in l -CBA. • Two out of the three sera that were reactive to the adult AchR showed also binding to the fetal AchR. • The cohort of conventionally tested triple seronegative patients studied is representative when compared to clinical data from the German myasthenia gravis registry. Autoantibody testing is the mainstay in confirming the diagnosis of autoimmune myasthenia gravis (MG). However, in approximately 15% of patients, antibody testing in clinical routine remains negative (seronegative MG). This study aimed at assessing the prevalence of "clustered" AChR- and MuSK- and LRP4- autoantibodies using a live cell-based assay in a large German cohort of seronegative myasthenia gravis (SNMG) patients. A total of 67 SNMG patients were included. Clustered AChR-ab were identified in 4.5% (n = 3) of patients. Two out of the three patients showed binding to the adult AchR as well as the fetal AchR. None of the patients was positive for MuSK- or LRP4-autoantibodies. There were no differences in clinical characteristics between the patients with and without clustered AChR-ab detection. Comparison of clinical data of our cohort with clinical data from the nationwide Myasthenia gravis registry showed broad similarities between seronegative MG patients of both cohorts. [ABSTRACT FROM AUTHOR]

The factors determining whether infection will occur following exposure to SARSCoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen – single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Study was conducted with aim of comparing subtypes types of NMOSD based on serology. Methods: In this retrospective study, patients ≥18 years were included satisfying IPND 2015 criteria. Three groups were created based on seropositivity for AQP4 antibody, MOG antibody or double seronegative. Demographic, clinical and imaging were compared using regression analysis. Results: Forty-six patients, 28 (60.9%) AQP4+, 11 (23.9%) MOG + and remaining 7 (15.2%) double seronegative were included. Thirty-seven patients (80.4%) had presenting symptoms localized to optic nerve and/or cord [AQP4 + 22 (78.5%), MOG + 9 (81.8%) and double seronegative 6 (85.7%)]. Presentation with bilateral optic neuritis was more common in AQP4- patients. Twenty (86.8%) out of the 23 patients who had relapsing disease localized to optic nerve and/or spinal cord [AQP4 + 13/14 (92.8%), MOG + 3/5 (60%) and double seronegative 4/4 (100%)]. Relapses were more common in AQP4+ (77% vs 12% vs10%). In AQP4 negative group disability (EDSS 4.2 vs 3.3) and progression index was relatively less (1.6 vs 1.1). CSF pleocytosis (38.8% vs 17.9%) and raised proteins (66.6% vs 32.1%) were also more common. Optic nerve MRI (>50% optic nerve and chiasma involvement) was more commonly abnormal in AQP4 negative (52.9% vs 31.2%). Regression analysis revealed females to be significantly higher in AQP4 positive NMOSD (89.3%) when compared to MOG positive (36.4%) and double seronegative (42.9%). Conclusion: Gender was the only significant difference between the three groups. There was trend towards greater disability and more relapses in AQP4 + groups.

Abstract Background Seronegative antiphospholipid syndrome (SN-APS) is often defined as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a different note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifestations without non-criteria features/aPL positivity (controls). Methods Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospitals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared. Results A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2–6.5, p

The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen – single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.

This case-control study was conducted to determine the antibody titer against the measles virus in childhood cancer survivors' post-chemotherapy treatment to determine the patient's immune status against the measles virus. We enrolled 38 children who were in complete remission and whose treatments had been stopped for at least 3 months and 38 age and sex-matched healthy controls. We analyzed the medical records of the cancer survivors, and each study participant's serum sample was analyzed by the ELISA method to determine the antibody titer against measles. The cancer survivors had significantly lower measles antibody titers than the healthy control participants, and 78.9% of cancer survivors were unprotected (seronegative) compared to 7.9% in healthy controls. After multivariate analysis, there was no statistically significant factor associated with loss of protective humoral immunity against measles. These results underline the need for post-chemotherapy measles antibody testing and revaccination of seronegative survivors. [ABSTRACT FROM AUTHOR]

Background: To investigate the frequency of difficult-to-treat (D2T) rheumatoid arthritis (RA) in patients early escalated to biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) after failure of treat-to-target with methotrexate (MTX)., Methods: From a prospective cohort of early RA, all patients with their first access in the years 2005-2018, and eventually starting a b/tsDMARD before the end of 2022, were included and followed-up until April 2024. Study outcomes included drug survival on each consecutive b/tsDMARDs, development of D2T (according to the EULAR definition and subsequent modifications), and its predictors., Results: Of a total cohort of 722 early RA patients treated with initial MTX and followed-up for at least 3 years from diagnosis, 155 (21.5%) had started a b/tsDMARD after a median of 19 months. In more than 70% of the cases, RA was uncontrolled despite optimal doses of MTX of ≥ 15 mg/day. The retention rates of the first and the second b/tsDMARD were approximatively 70% after 1 year but dropped to 40% after 5 years. After a median (IQR) follow up of 72.6 (34.5-134.2) months, 45 patients (29%) fulfilled the EULAR D2T criteria. At multivariable analysis, higher number of swollen joints and worse pain scores were confirmed as predictors of D2T. Furthermore, in this early RA cohort, shorter disease duration at the start of treatment with b/tsDMARDs, together with negativity for autoantibodies, were also independent predictors of D2T., Conclusions: Early implementation of treatment after failure of treat-to-target with MTX may not prevent the development of D2T in RA. Patients showing early refractoriness to conventional drugs and those lacking autoantibodies are at higher risk of multiple treatment failures., (© 2024. The Author(s).)

Abstract Background Diagnosing seronegative rheumatoid arthritis (RA) can be challenging due to complex diagnostic criteria. We sought to discover diagnostic biomarkers for seronegative RA cases by studying metabolomic and lipidomic changes in RA patient serum. Methods We performed comprehensive metabolomic and lipidomic profiling in serum of 225 RA patients and 100 normal controls. These samples were divided into a discovery set (n = 243) and a validation set (n = 82). A machine-learning-based multivariate classification model was constructed using distinctive metabolites and lipids signals. Results Twenty-six metabolites and lipids were identified from the discovery cohort to construct a RA diagnosis model. The model was subsequently tested on a validation set and achieved accuracy of 90.2%, with sensitivity of 89.7% and specificity of 90.6%. Both seropositive and seronegative patients were identified using this model. A co-occurrence network using serum omics profiles was built and parsed into six modules, showing significant association between the inflammation and immune activity markers and aberrant metabolism of energy metabolism, lipids metabolism and amino acid metabolism. Acyl carnitines (20:3), aspartyl-phenylalanine, pipecolic acid, phosphatidylethanolamine PE (18:1) and lysophosphatidylethanolamine LPE (20:3) were positively correlated with the RA disease activity, while histidine and phosphatidic acid PA (28:0) were negatively correlated with the RA disease activity. Conclusions A panel of 26 serum markers were selected from omics profiles to build a machine-learning-based prediction model that could aid in diagnosing seronegative RA patients. Potential markers were also identified in stratifying RA cases based on disease activity.

Ahmed Seri,1,2 Hala Kamal Ali Mohamed,3– 5 Mohammed Elmujtba Adam Essa,6 Elnour Mohammed Elagib,7,8 Noha Ibrahim Ahmed Eltahirm,7,8 Salma Mohammed Alfatih Mansour,9 Abdelkareem A Ahmed6 1Department of Clinical Immunology, Royal Care International Hospital, Khartoum, Sudan; 2Department of Immunology, Institute of Endemic Disease, University of Khartoum, Khartoum, Sudan; 3Department of Microbiology, Faculty of Medicine, African International University (AIU), Khartoum, Sudan; 4Department of Clinical Immunology, Sudan Medical Specialization Board (SMSB), Khartoum, Sudan; 5Faculty of Medicine, Sudan University of Science and Technology, Khartoum, Sudan; 6Department of Clinical Medicine, Medical and Cancer Research Institute, Nyala, Sudan; 7Department of Rheumatology, Omdurman Military Hospital, Khartoum, Sudan; 8Department of Medicine, Faculty of Medicine, Karary University, Khartoum, Sudan; 9Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum, SudanCorrespondence: Mohammed Elmujtba Adam EssaDepartment of Clinical Medicine, Medical and Cancer Research Institute, Nyala, SudanTel +249 90700938Email Awadali818@yahoo.comIntroduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovial membrane. RA is classified as seropositive or seronegative, according to the absence or presence of primarily IgM RF, RF, and/or ACPA. The aim of this study is to identify the relationship between the serotype of rheumatoid arthritis and the level of ESR.Methods and Materials: This is a descriptive, cross-sectional study done in Omdurman military hospital, Khartoum, Sudan. Conducted with 60 patients with RA, data were collected through a designated questionnaire which included demographic, age, gender, duration of the disease, laboratory finding. All the patients in the study were treated with conventional DMARDs and diagnosed according to the 2010 ACR/EULAR criteria; their disease activity status was assessed by DAS28/ESR. Data were analyzed using SPSS version 23.Results: The study found that 91.7% of the patients were females, patients of age group between 36 and 50 years had the highest percentage at 38.3% followed by those between 51 and 70 years and the least age group between 20 and 35 years, 36.7% and 15%, respectively. Of all the patients 61.7% were found to be SPRA, while the remaining 38.3% were seronegative (SNRA). Altogether 55% of the patients had moderate disease activity, followed by 16.7% who had a remission, 15% had high disease activity and the remaining 13.3% had low disease activity. The metacarpophalangeal (MCP) joint was found to be the only joint that was significantly associated with DAS28 and its involvement was greater among seropositive patients. The most affected joints were found to be shoulders, knees, wrist, MCP, PIP and elbow, in that order.Conclusion: Females, middle-age group and shoulder joint were the most affected. Most RA was found to be SPRA, and the seropositive group was found to be more associated with high disease activity, while the seronegative group was associated with remission and low disease activity.Keywords: seropositive, seronegative, RA, female, high disease activity

Simple Summary: Toxoplasmosis is a zoonotic disease caused by T. gondii infection. The main aims of this study were to assess the seropositivity to toxoplasmosis of an exotic breed of cattle (n = 400) from different farms using the Latex Agglutination Test, validate the Cattle Toxo IgG ELISA kit with the help of the commercially available ELISA kit and compare the efficacy of the LAT and Cattle Toxo IgG ELISA kit for assessing seropositivity of cattle to toxoplasmosis. Four hundred cattle sera were collected from an exotic breed of cattle in Pakistan. These sera were evaluated through an LAT and Cattle Toxo IgG ELISA kit. Of 400 samples, 90 were elected and screened through a commercially available ELISA kit. The sensitivity and specificity of the Cattle Toxo IgG ELISA kit came out to be 100% and 96.15%, and in LAT, it was found as 26.31% and 61.53%, respectively. The Cattle Toxo IgG ELISA kit revealed 29.75% (119/400) seropositivity, 6% less than that found through LAT. The results of this study show that Cattle Toxo IgG ELISA kit is a highly accurate and reliable serodiagnostic tool to diagnose bovine toxoplasmosis. Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis in warm-blooded vertebrates, globally. The main aims of this study were to assess the seropositivity to toxoplasmosis of an exotic breed of cattle (n = 400) from different farms using the Latex Agglutination Test and validate Cattle Toxo IgG ELISA kit. Of a total of 400 cattle sera that were evaluated by LAT, 143 (35.75%) were found positive. Based on these data, 90 samples (n = 60 seronegative by LAT; n = 30 seropositive by LAT) were elected for screening through a commercially available ELISA kit. The same 90 samples were screened through a Cattle Toxo IgG ELISA kit for validation purposes. Of 90 samples, 40 were seropositive in the Cattle Toxo IgG ELISA kit (100% sensitivity), and 38 were seropositive in a commercially available ELISA kit. All 50 samples in the Cattle Toxo IgG ELISA kit (96.15% specificity) were also seronegative in the commercially available ELISA kit. Hence, the sensitivity and specificity of the Cattle Toxo IgG ELISA kit came out to be 100% and 96.15%, and in LAT, it was found as 26.31% and 61.53%, respectively. Therefore, the Cattle Toxo IgG ELISA kit is a highly reliable serodiagnostic tool to diagnose bovine toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background & objectives: Serosurvey of COVID-19 provides a better estimation of people who have developed antibodies against the infection. Undertaking such a serosurvey in certain districts of India which are densely populated with prominent tribes can provide valuable information regarding seropravelance of SARS-CoV-2 antibodies among such indigenous populations. In this context, two rounds of population-based, cross-sectional serosurveys for SARS-CoV-2 IgG antibody were carried out in Jharkhand, a tribal-dominated State of India, to compare the seroprevalence of SARS-CoV-2 infection and to determine the associated demographic risk factors. Methods: The surveys were carried out in June 2020 and February 2021 in ten districts of the State of Jharkhand. Blood samples were collected from the residents of the selected districts by random sampling and tested for anti-SARS-CoV-2 antibodies using an automated chemiluminescence immunoassay platform. A total of 4761 and 3855 eligible participants were included in round 1 and round 2, respectively. Results: The age- and gender-standardized seroprevalence for COVID-19 during round 1 was 0.54 per cent (0.36-0.80) that increased to 41.69 per cent (40.16-43.22) during round 2 with a gap of eight months in between. The seropositivity among male and female participants was 0.73 and 0.45 per cent, respectively, during the first round and 51.35 and 33.70 per cent, respectively, during the second round. During the first round, 17.37 per cent of the participants were tribal with seropositivity of 0.24 per cent (0.02-0.87), and during the second round, 21.14 per cent were tribal with seropositivity of 39.14 per cent (35.77-42.59). Compared to tribal group, non-tribal participants had an adjusted odds of 1.24 (95% confidence interval=1.04-1.48) for SARS-CoV-2 seropositivity. Interpretation & conclusions: COVID-19 seroprevalence was found to be low during the first round (0.54%) of the survey, possibly due to the travel restrictions during lockdown better adherence to social distancing and wearing of face masks among the people. Understanding the dynamics of SARS-CoV-2 transmission and the susceptibility to infection at the individual as well as community level will inform decision and help policy makers to design and implement effective public health strategies to mitigate the pandemic in this State. [ABSTRACT FROM AUTHOR]

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10–15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study. We identified 15 seronegative MG patients with 17 MCs and 142 AChR-MG with 159 MCs. Seronegative MCs were younger (54.3 ± 14.5 vs 66.5 ± 16.3 years; p = 0.0037), had a higher rate of thymus hyperplasia (29.4% vs 3.1%; p = 0.0009), and were more likely to be female (58.8% vs 37.7%; p = 0.12) compared to AChR-MCs. Time between diagnosis of MG and MC was significantly longer in seronegative patients (8.2 ± 7.6 vs 3.1 ± 4.4 years; p < 0.0001). We found no differences in duration of mechanical ventilation (16.2 ± 15.8 vs 16.5 ± 15.9 days; p = 0.94) and length of stay at intensive care unit (17.6 ± 15.2 vs 17.8 ± 15.4 days; p = 0.96), or in-hospital mortality (11.8% vs. 10.1%; p = 0.69). We conclude that MC in seronegative MG affects younger patients after a longer period of disease, but that crisis treatment efficacy and outcome do not differ compared to AChR-MCs. [ABSTRACT FROM AUTHOR]

Following a rubella outbreak in 2011, Vietnam implemented a mass measles-rubella vaccination campaign for children aged 1–14 years in 2014–2015, further expanding the target age to 16–17 years in 2016; routine vaccination was introduced in 2014. However, there was concern that a substantial proportion of women of child-bearing age were still susceptible to rubella, with the fear of congenital rubella emergence. Thus, we conducted a prospective cohort study in Nha Trang, Vietnam, from 2017–2018 to investigate pregnant women’s susceptibility to rubella infection, the incidence of congenital rubella infection, and factors associated with susceptibility. Cord blood was tested for rubella-specific immunoglobulin M (IgM) and IgG; neonatal saliva and cord blood specimens were examined for rubella-RNA. We analyzed 2013 mother-baby pairs. No baby was rubella-IgM or rubella-RNA positive. Overall, 20.4% of mothers were seronegative (95% confidence interval, 18.6%–22.1%). The seronegativity was significantly low among mothers aged