Elevated Antibody Research Articles

Multiplex assays to determine correlation of binding and neutralizing antibodies following SARS-CoV-2 infection and vaccination

Abstract The COVID-19 pandemic has led to the rapid development of many different therapeutics and vaccines to reduce the burden of the disease. Most vaccines target the highly immunogenic spike (S) protein for generating functional immune responses to block the entry of the virus into host cells. However, the mutations in the S-protein have led to the emergence of many variants that escape the immune response. We developed two multiplex assays using Luminex® xMAP® technology to assess antibody profiles after infection and vaccination; 1) to quantify the binding antibodies against SARS-CoV2 receptor binding protein (RBD), nucleocapsid protein (NP), S1-protein (S1), and Trimer having S1, S2, and extracellular domain protein; 2) a multiplex surrogate virus neutralization antibody assay targeting CoV2 wild type and various mutant viruses. The quantitative binding assay uses the WHO standard for determining the binding antibody unit (BAU)/mL. Surrogate virus neutralization assay measures the inhibition of ACE2 protein binding to wild-type and S protein variants coupled to beads in the presence of immune or convalescent sera. We determined the negative threshold using 81 pre-pandemic serum samples collected during 2017–18. We used 116 samples collected from 45 vaccinated and 15 infected subjects for antibody quantification. Binding antibodies to RBD, S1, and trimer were higher in vaccinated individuals with minimal reactivity to NP, whereas the NP antibody response was higher in the infected individuals. We observed a direct correlation between spike protein binding and neutralizing antibodies using the two assays. We saw the most elevated neutralization antibodies against variants from individuals with breakthrough infections.

Autoantibodies produced by SARS-CoV-2 infection trigger damage to the lacrimal and salivary glands and lead to the development of Sjögren’s Disease

Abstract Sjögren’s Disease (SjD) is a chronic, systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and mouth as the result of the secretory dysfunction of the lacrimal and salivary glands. In recent years, infectious agents have been shown to be associated with SjD. Several studies indicated that SARS-CoV-2 infection induces autoantibodies production, patients also experienced various autoimmune disorders. This study used SARS-CoV-2 WA1/2020 to infect hACE2 mice to investigate the relationship between SARS-CoV-2 infection and SjD. Infected mice showed dry eyes, decreased salivary flow, lymphocytic infiltration of the lacrimal and salivary glands, elevated antinuclear antibodies (ANA), specifically anti-SSB/La, and apoptotic cells near the acinar cells. Notably, counting of apoptotic cells showed a significantly higher number in the lacrimal glands of mice infected with a low viral load than high viral load. We confirmed with clinical data that we observed the elevation of SjD-specific autoantibodies (ANA, anti-SSB/Ro52, and anti-SSA/La) in sera from COVID-19 patients. Salivary gland biopsies of patients diagnosed with SjD several months after SARS-CoV-2 infection also showed lymphocytic infiltration and fibrosis. Lastly, to identify whether monoclonal antibodies produced by COVID-19 patients are reactive against nuclear antigens, antibodies tested for greater antiviral binding capacity were shown to be more responsive. Overall, by observing SjD-like phenotypes in mouse models and patients, our study confirms a direct pathogenic role of SARS-CoV-2 in SjD. It also provides a different pilot for the study of the mechanisms of autoimmune responses induced by viral infections. This research was funded by the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR), Division of Extramural Research (DE028544, PI-Nguyen; DE028544-02S1, PI-Nguyen), and the NIH/NIDCR Division of Intramural Research (Z01-DE000704, PI-Warner; Z01-DE00695, PI-Chiorini).

OC-STAMP-reactive IgG auto-antibody may upregulate osteoclastogenesis in association with elevated anti-P. gingivalisantibody

Abstract Objectives: Periodontal disease (PD) is a polymicrobial inflammatory lesion in which pathogenic bone loss is caused by osteoclasts (OC) differentiated from MCSF/RANKL-primed monocytes. Elevated IgG antibody to a keystone opportunistic pathogen, Porphyromonas gingivalis (Pg), is a hallmark humoral response in PD that is correlated with pathogenic bone loss. Whereas, a cell membrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), is engaged in cell-fusion event required for OC-genesis. This study examined the humoral immune responses to OC-STAMP expressed by human monocytes in relation to anti-Pg antibody. Methods: Blood serum (N=10) collected from systemically healthy human subjects (Precision for Medicine) were measured for IgG antibody titer to Pgor OC-STAMP peptides. Human peripheral blood mononuclear cells were stimulated with MCSF/RANKL with or without anti-OC-STAMP rabbit polyclonal antibody or control rabbit IgG. Affinity purified human anti-OC-STAMP antibody was also tested for its activity to alter the OC-genesis. OC-genesis induced in vitrowas evaluated by TRAP staining and pit formation assay. Results: IgG antibody titer to Pgpositively correlated with that to human OC-STAMP peptides (r=0.579, p<0.05). Anti-OC-STAMP auto-antibody purified from human serum with high IgG antibody titer to Pg, as well as anti-OC-STAMP rabbit antibody significantly promoted in vitroOC-genesis (p<0.05). Conclusions: The results indicated that Pginfection may be associated with development of anti-OC-STAMP auto-antibody which can promote OC-genesis, suggesting a novel immunological intervention in the pathogenesis of PD. Supported by grants from NIH NIDCR grants, DE-027851, DE-028715 and DE-331851

Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) as a differential diagnosis of Creutzfeldt-Jakob disease.

Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) is characterised by a wide range of neuropsychiatric symptoms and elevated thyroid antibodies. SREAT can mimic sporadic Creutzfeldt-Jakob disease (sCJD) and distinguishing between both entities is important because SREAT responds to corticosteroids. Data of patients reported to the National Reference Centre for the Surveillance of CJD in Göttingen, Germany between August 1994 and October 2008 was retrospectively reviewed. In the case and control groups, 49 patients had SREAT and 48 had sCJD with elevated thyroid antibodies. Antibodies against thyroid peroxidase were the most common antibodies in both SREAT (86%) and sCJD (88%), followed by antibodies against thyroglobulin (SREAT, 63.3%; sCJD, 39.6%; p = 0.020) and TSH-receptor-antibodies (SREAT, 14.3%; sCJD, 2.1%; p = 0.059). Epileptic seizures were observed more frequently in the SREAT group (SREAT, 44.9%; sCJD, 12.5%; p < 0.001). Dementia (SREAT, 61.2%; sCJD, 100%; p < 0.001), ataxia (SREAT, 44.9%; sCJD, 89.6%; p < 0.001), visual impairment (SREAT, 22.4%; sCJD, 50%; p = 0.005), extrapyramidal disorder (SREAT, 32.7%; sCJD, 60.4%; p = 0.006), myoclonus (SREAT, 38.8%; sCJD, 81.3%; p < 0.001) and akinetic mutism (SREAT, 6.1%; sCJD, 37.5%; p < 0.001) were observed more frequently in sCJD. Cerebrospinal fluid (CSF) pleocytosis was observed more frequently in SREAT patients (SREAT, 33.3%; sCJD, 6.4%; p = 0.001), as was a pathological increase in protein concentration (SREAT, 68.8%; sCJD, 36.2%; p = 0.001). In a case of encephalopathy, the diagnosis of SREAT should also be considered in suspected cases of CJD so as to be able to start corticosteroid treatment quickly.

A Rare Case of Thymoma-Associated Idiopathic Inflammatory Myopathy and Myasthenia Gravis (P1-5.009)

<h3>Objective:</h3> To describe the phenotype of and to support further research into the etiology and appropriate therapeutic management of thymoma-associated myasthenia gravis (MG)-inflammatory myopathy (IM) overlap syndrome. <h3>Background:</h3> While rare, the combination of MG and idiopathic IM has been previously documented. The prevalence of thymoma in patients with both IM and MG (70%) is significantly higher than in those with MG alone (10%). It has been postulated that thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway, may increase the risk of idiopathic IM and MG. <h3>Design/Methods:</h3> A 47-year-old male with a history of thymoma complicated by recent tumor recurrence presented to our tertiary referral center with rapid deterioration in bulbar and appendicular motor strength and a presumed diagnosis of amyotrophic lateral sclerosis. Prednisone, pyridostigmine, and IVIG previously provided no relief. Further workup was undertaken to elucidate the true etiology of his symptoms. <h3>Results:</h3> Electromyography/nerve conduction study was unremarkable. CSF studies revealed a normal protein and cell count. Creatine kinase was elevated at 2578 units/L. MRI of his cervical spine was remarkable for inflammatory changes along the myofascial planes of the posterior paraspinal muscles, concerning for myositis. Neural autoantibody testing, albeit after he had received IVIG, revealed multiple positive findings including acetylcholine receptor (AChR) blocking and modulating, smooth muscle, F-Actin, fibrillarin, and voltage-gated potassium channel antibodies. High dose methylprednisolone and plasmapheresis were initiated with marked clinical improvement. He has since been maintained on rituximab. On follow-up testing, continued positive antibodies include AChR binding, AChR blocking, and elevated striated muscle antibody. <h3>Conclusions:</h3> When presented with a patient with a history of recurrent thymoma and weakness of unclear etiology, MG-IM overlap syndrome should be considered in the differential diagnosis. Further study into the mechanism and appropriate management of this autoimmune dysregulation syndrome should be undertaken. <b>Disclosure:</b> Dr. Schmoll has nothing to disclose. Dr. Rodenbeck has nothing to disclose.

Use of Efgartigimod in Treatment of Myasthenia Gravis Relapse after Possible Recurrence of Invasive Thymoma: A Case Report. (P1-5.011)

<h3>Objective:</h3> NA <h3>Background:</h3> Myasthenia gravis is an autoimmune neuromuscular junction disorder with established association with thymoma. There is no consensus on optimal treatment of recurrent thymoma post-resection. Efgartigimod is a first-in-class FcRn antagonist approved by the FDA in December 2021 for treatment of AChR-antibody-positive adults with generalized MG. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 53-year-old right-handed man presented to us in September 2020 with a 10-month history of recurrent diplopia, ptosis, dysarthria, dysphagia, and bilateral hand weakness. Workup for MG revealed blocking, binding, and modulating AChR antibodies. CT scan of his chest demonstrated an invasive anterior mediastinal mass. He started pyridostigmine, mycophenolate and prednisone, and underwent a sternotomy with thymectomy with sparing of the directly adjacent right phrenic nerve in October 2020. Histopathology revealed a locally invasive Masaoka stage IIIA, pT1bN0M0, WHO type B2 thymoma. He received adjuvant radiotherapy until January 2021. He was weaned off prednisone and pyridostigmine by May 2021. He remained asymptomatic for about 18 months post-thymectomy except for transient dysarthria in September 2021 attributed to missed mycophenolate doses. Patient noticed recrudescence of bulbar and respiratory symptoms around April 2022. Tests showed elevated AChR antibodies but surveillance chest CT scans did not demonstrate tumor recurrence or metastases. His cardiothoracic surgeon remained suspicious of residual thymoma. He started efgartigimod in July 2022 which he tolerated well, resulting in symptom resolution and objective improvement on MG-specific outcome measures (MG-ADL, MG-QoL15r and MGC). His symptoms recurred during a COVID-19 infection a month later, but he rapidly became asymptomatic after completing the second efgartigimod cycle in September 2022. <h3>Conclusions:</h3> Our patient with AChR antibody-positive, thymoma-associated, generalized MG with recurrent symptoms despite mycophenolate treatment, thymectomy and radiotherapy showed a dramatic response to initial cycles of efgartigimod therapy without significant adverse effects. We propose that efgartigimod be considered early in the management of MG patients with recurrent symptoms after thymectomy. <b>Disclosure:</b> Dr. Akemokwe has stock in CVS HEALTH CORP. Dr. Akemokwe has stock in LABORATORY CORP AMERICAN HOLDINGS. Dr. Coskun has nothing to disclose. Dr. Meyerson has nothing to disclose. Dr. Ebong has nothing to disclose.

Horner’s Syndrome as an Atypical Presentation of Neuroborreliosis: A Case Report and Review of Literature (P1-9.006)

<h3>Objective:</h3> To localize and report postganglionic Horner’s syndrome as an unusual presentation of neuroborreliosis. <h3>Background:</h3> Lyme disease is the most common tick-born infection in the United Sates with ~30,000 reportable cases yearly, 10–15% involving the nervous system. Neuroborreliosis has a heterogenous spectrum of clinical manifestations. Currently, there are few case reports of associated Horner’s syndrome. Localization has not been well described with no cases reporting positive imaging findings. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 50-year-old healthy woman presented with four days of high-grade fever and left-sided headache followed by one day of left droopy eyelid. Symptoms developed two weeks after an outdoor summer trip to Massachusetts with exposure to insect bites. Her neurologic exam demonstrated 2mm left-sided ptosis, miosis with a briskly reactive right pupil from 6-to-2mm and left pupil from 3-to-2mm in the dark, and 2mm-difference in pupil size in the light with a smaller left pupil. She also developed macular patches over the head and trunk consistent with multifocal erythema migrans. Initial laboratory work-up showed mild anemia, thrombocytopenia, and elevated transaminase levels. MRI of brain and orbits with contrast revealed asymmetric enhancement within the left cavernous sinus and superior orbital fissure with mild edema of the left extraocular muscles. MRA/MRV did not show evidence of cavernous sinus thrombosis, carotid-cavernous fistula, or other abnormalities. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with negative Borrelia species detection by PCR. Further testing revealed elevated serum total Lyme antibody and Western blot IgM suggestive of Lyme neuroborreliosis. Patient was treated with oral doxycycline with resolution of symptoms. <h3>Conclusions:</h3> Neuroborreliosis has a highly variable clinical presentation. This case illustrates and localizes an isolated Horner’s syndrome as a masquerading presentation of neuroborreliosis. Therefore, clinical suspicion and early recognition are important, especially in the setting of a convincing history, to prompt early diagnosis and initiation of treatment and to prevent disease progression. <b>Disclosure:</b> Dr. Bou Reslan has nothing to disclose. Dr. Park has nothing to disclose. Dr. Sabadia has nothing to disclose. Dr. Grossman has nothing to disclose. The institution of Dr. Zakin has received research support from American Board of Psychiatry and Neurology.

Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome.

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Antibody titer after administration of mRNA-based vaccine against severe acute respiratory syndrome coronavirus 2 in liver transplant recipients.

The mRNA-based vaccine was released as a COVID-19 prophylactic; however, its efficacy in organ transplant recipients is unknown. This study aimed to clarify this in liver transplant recipients. Herein, liver transplant recipients from two hospitals who received vaccines were included. Immunoglobulin-G antibodies against the spike and nucleocapsid proteins were measured chronologically after the second, third, and fourth vaccine doses. Antibody levels in 125 liver transplant recipients and 20 healthy volunteers were analyzed. The median age at transplant was 35 (interquartile range 1, 53) years, and the period between transplant and the first dose was 15.2 ± 7.7 years. After the second and third doses, 89.1% and 100% of recipients displayed a positive humoral response, respectively. Anti-spike antibodies after the second dose were significantly reduced at 3 and 6 months, compared to that at 1 month (26.0 [5.4, 59.5], 14.7 [6.5, 31.4] vs. 59.7 [18.3, 164.0] AU/mL, respectively, p < 0.0001). However, a booster vaccine significantly elevated anti-spike antibodies in LT recipients (p < 0.0001) as well as in healthy controls (p < 0.0001). Additionally, the decay rate was comparable between the transplant recipients and controls (2.1 [0.8, 4.5] vs. 2.7 [1.1, 4.1] AU/mL/day, p = 0.9359). Only 4.0% of vaccinated transplant recipients were positive for anti-nucleocapsid antibodies. Liver transplant recipients can acquire immunity similar to that of healthy people through vaccination against SARS-CoV-2. The antibody decay rate is the same, and booster vaccinations should be administered similarly to that in healthy individuals.

Elevated Antibody Titers to Epstein-Barr Virus and Cytomegalovirus in Patients with Drug-Induced Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which has been associated with Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection. Drug-induced lupus (DIL) is a lupus-like disease caused by the intake of therapeutic drugs, which has been estimated to cause approximately 10-15% of lupus-like cases. Although SLE and DIL share common clinical symptoms, there are some fundamental differences between DIL and SLE onset. Moreover, it remains to be examined whether environmental factors, such as EBV and CMV infections, may contribute to the development of DIL. This study focused on examining the possible association between DIL and EBV and CMV infections, by examining IgG titers to EBV and CMV antigens in serum samples by enzyme-linked immunosorbent assays. Antibody titers to EBV early antigen-diffuse and CMV pp52 were found to be significantly elevated in both SLE and DIL patients compared to healthy controls, although no correlation was found for antibodies to the two virus antigens in the respective disease groups. Moreover, total IgG titers were reduced in SLE and DIL serum samples, which may reflect a general lymphocytopenia, which commonly is associated with SLE. The current findings support that EBV and CMV infections may contribute to the development of DIL and that onset of both diseases are related.

Prevalence and associated risk factors of Toxoplasma gondii infection in sheep and aborted women in Egypt

Toxoplasmosis has been associated with economic and public health concerns due to abortion in humans and animals. Detection for the presence of anti-Toxoplasma gondii antibodies in sera of 174 healthy sheep (IgG) and sera of 89 aborted women (IgG, IgM, and IgG avidity) using enzyme-linked immunosorbent assay and T. gondii in 59 sheep milk samples identified by PCR. The primary risk factors for sheep and women seropositive samples were also analyzed. Relatively higher seroprevalence of T. gondii, 62.6%, was recorded in sheep than 57.3% in aborted women. The IgM/IgG antibody responses in aborted women were 42.7%, 41.6%, 15.7%, and 0% for IgM -ve/IgG -ve (negative toxoplasmosis), IgM -ve/IgG +ve (chronic toxoplasmosis), IgM +ve/IgG +ve (maternal infection) and IgM +ve/IgG -ve (acute infection), respectively. IgM and IgG-positive samples showed a low avidity rate 14.3%, denoting acute maternal infection, while a much higher rate 78.6%, denoting chronic maternal infection. Molecular investigation of T. gondii in sheep milk samples revealed that 28.8% were positive by PCR at 470-bp. The respectable significant association between many risk factors and the seroprevalence of T. gondii in humans and sheep was recorded. The current study indicates elevated toxoplasmosis antibodies in sheep and aborted women from El-Beheira and Alexandria governorates, Egypt. Additionally, it demonstrates a correlation between age, mutton intake, miscarriage, cat exposure, drinking water source, and breeding practices with seropositivity to T. gondii. These results largely confirm the need for greater in-depth toxoplasmosis epidemiological research and public health education initiatives.

Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model

Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 2016 Zika virus (ZIKV) outbreak, rapid availability of vaccines can prove critical in reducing widespread disease burden. The recent successes of mRNA vaccines support their evaluation in pregnant animal models to justify their use in neonatal settings. Here we evaluated immunogenicity of self-amplifying replicon (repRNA) vaccines, delivered with our clinical-stage LION nanoparticle formulation, in pregnant rabbits using ZIKV and HIV-1 as model disease targets. We showed that LION/repRNA vaccines induced robust antigen-specific antibody responses in adult pregnant rabbits that passively transferred to newborn kits in utero. Using a matrixed study design, we further elucidate the effect of vaccination in kits on the presence of pre-existing maternal antibodies. Our findings showed that timing of maternal vaccination is critical in maximizing in utero antibody transfer, and subsequent vaccination in newbornsmaintained elevated antibody levels compared with no vaccination. Overall, our results support further development of the LION/repRNA vaccine platform for maternal and neonatal settings.

Role of age in dynamics of autoantibodies in pediatric Celiac disease

BackgroundCeliac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis.MethodsCD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts.ResultsCD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60–8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81–11.06]) and 62 (median age: 9.5 [IQR: 6.26–12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47–6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups.ConclusionCD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.

Incidence of Antiphospholipid Syndrome: Is Estimation Currently Possible?

Antiphospholipid syndrome is a systemic autoimmune disorder characterized by vascular thrombosis and/or obstetric events in association with persistently elevated antiphospholipid antibodies. Antiphospholipid syndrome is typically considered a rare disease, but the true incidence is uncertain owing to the diverse antiphospholipid antibody-related clinical manifestations, inconsistent definitions of antiphospholipid antibody positivity, under-recognition of the disease, and limited population-based studies. Published estimates of the incidence of antiphospholipid syndrome range from approximately 2 to 80 per 100 000 person-years. A targeted literature review and applied methodology were performed to derive a best available estimate. Significant limitations of the published literature were observed, some of which have been previously reported. The incidence of antiphospholipid syndrome in the United States was estimated to be approximately 7.1 to 13.7 per 100 000 person-years in the general population. Although this estimate is likely more accurate than previously reported estimates, large, contemporary, population-based studies that reasonably adhere to the antiphospholipid syndrome classification criteria are needed to further refine estimates of the incidence of antiphospholipid syndrome.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies

ObjectiveDetection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. MethodsWe performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb−) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. ResultsPatients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. ConclusionWe conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

About a case: affective psychosis and hyperthyroidism

IntroductionHyperthyroidism due to Graves-Basedow disease is a common cause of neuropsychiatric manifestations, such as anxiety, psychomotor restlessness, mood disturbances, insomnia and psychosis. Hashimoto’s encephalopathy rarely occurs in so-called autoimmune thyroiditis, which can present with hyperthyroidism and neuropsychiatric symptoms similar to Graves’ disease. We add that the mystical-religious beliefs, present in all human cultures, and decisive in the case at hand, make us propose an evolutionary origin of them.ObjectivesClinical case descriptionMethodsA clinical case based on medical reports is describedResultsWe present the case of a 72-year-old woman, a member of the Seventh-day Adventist Church, well adapted to the Community. Known history of elevated antithyroid antibodies since 2019, brought to the emergency room involuntarily due to a mystical-religious delusional condition associated with behavioral disturbance. On examination, cachectic appearance, distal tremor, emotional exaltation and megalomanic speech were highlighted. Laboratory tests revealed primary hyperthyroidism with elevated antibodies. During admission, the differential diagnosis between Graves-Basedow disease and Hashimoto’s encephalopathy was considered. Thyroid scintigraphy oriented the diagnosis to Graves-Basedow disease, not requiring lumbar puncture or corticosteroid treatment. Treatment was based on high-dose antithyroid and antipsychotic drugs, with clinical and analytical remission at 3 weeks. The patient was referred to a Social Health Center for functional recovery. The family refers to a similar episode in 2014, of less intensity and self-limited, which is proposed to be a hashitoxicosis.ConclusionsDifferential diagnosis between Graves-Basedow and Hashimoto disease is essential as they differ in treatment and prognosis. The continuity that the delusion presents with the previous beliefs of the patient, differing mainly in the affective-behavioral implication, makes us consider a predisposition to psychosis in our patient. Religiosity can be adaptive in certain environments, since mystical beliefs have existed throughout the history of the human species and seem to be part of our nature.Disclosure of InterestNone Declared

Alpha-Gal Sensitization in a US Screening Population Is Not Associated With a Decreased Meat Intake or Gastrointestinal Symptoms.

Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms. We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015. We quantified serum alpha-gal immunoglobulin E antibodies in participants who were prospectively enrolled at screening colonoscopy and compared diet intake and lower GI symptoms reported in standardized questionnaires among those with elevated versus no alpha-gal IgE antibodies. Alpha-gal IgE antibodies were common-31.4% of screening colonoscopy participants (127 of 404) had elevated serum alpha-gal IgE >0.1 kU/L. Alpha-gal-sensitized participants endorsed similar rates of abdominal pain compared with those without alpha-gal antibodies (33% vs 38%, adjusted odds ratio 0.9, 95% confidence interval 0.7-1.3). Mammalian meat consumption did not differ based on alpha-gal sensitization status (average 1.43 servings/d in sensitized subjects vs 1.50 in alpha-gal IgE-negative subjects, P = 0.9). Alpha-gal-sensitized participants with levels ≥10 (n = 21) were overrepresented in the lowest quartiles of mammalian meat consumption, but not among those with GI symptoms in general. Participants with high alpha-gal antibody levels >2 kU/L (n = 45) or ≥10 U/L (n = 21) did not have a reduced mean daily mammalian meat intake compared with seronegative people. Elevated alpha-gal IgE antibodies were common and not associated with a reduced mammalian meat intake, abdominal pain, or diarrhea. Seropositivity did not predict symptomatic alpha-gal sensitization in this general screening population. Other host factors likely contribute to the phenotypic expression of alpha-gal syndrome.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC]=0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC=0.85, 95% CI=0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Recent advance in management of herpes simplex in Japan.

Herpes simplex, a common infection caused by the herpes simplex virus (HSV), is transmitted through contact of the skin/mucous membrane and establishes latency in the sensory ganglia for the rest of the life of the host. HSV occasionally reactivates and forms blisters around the lips or genitalia in some patients. Repeated overt symptoms, and, much more frequent, subclinical reactivation in the mucosa, make the host retain anti-HSV immunity continuously, resulting in maintaining steadily elevated antibody titer at any point after infection. Clinical symptoms differ in primary infection and recurrence. Primary infections sometimes manifest as severe symptoms such as fever and lymphadenopathy in addition to blisters/erosions of the skin, gingiva, lips, and oral mucosa, while recurrent herpes is generally mild. Diagnosing typical herpes simplex is not difficult, but when the course and manifestations are typical, definitive tests to identify HSV infection are limited since serology is not useful except with primary infection. For treatment, safe and effective oral antiviral drugs are available. Patient-initiated therapy is a new method of administration labeled in Japan. Amenamevir, an inhibitor of viral helicase primase, is available in Japan and labeled in addition to herpes zoster. These new diagnostic and therapeutic tools should be used for better management of herpes simplex.

Association between the quality of plant-based diets and periodontitis in the U.S. general population.

To investigate the relationship between plant-based diet indices (PDIs) and periodontitis and serum IgG antibodies against periodontopathogens in the U.S. We analysed cross-sectional data on 5651 participants ≥40 years of age from the Third National Health and Nutrition Examination Survey. Food frequency questionnaire data were used to calculate the overall PDI, healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Periodontitis was defined using a half-reduced Centers for Disease Control and Prevention and American Academy of Periodontology case definition. Serum antibodies against 19 periodontopathogens were used to classify the population into two subgroups using hierarchical clustering. Survey-weighted multivariable logistic regressions were applied to assess the associations of PDI/hPDI/uPDI z-scores with periodontitis and hierarchical clusters after adjusting for potential confounders. A total of 2841 (50.3%) participants were defined as having moderate/severe periodontitis. The overall PDI z-score was not significantly associated with the clinical and bacterial markers of periodontitis. By considering the healthiness of plant foods, we observed an inverse association between hPDI z-score and periodontitis (odds ratio [OR]=0.925, 95% confidence interval [CI]:0.860-0.995). In contrast, higher uPDI z-score (adherence to unhealthful plant foods) might increase the risk of periodontitis (OR=1.100; 95% CI: 1.043-1.161). Regarding antibodies against periodontopathogens, the participants in cluster 2 had higher periodontal antibodies than those in cluster 1. The hPDI z-score was positively associated with cluster 2 (OR=1.192; 95% CI: 1.112-1.278). In contrast, an inverse association between uPDI z-score and cluster 2 was found (OR=0.834; 95% CI: 0.775-0.896). Plant-based diets were associated with periodontitis, depending on their quality. A healthy plant-based diet was inversely related to an increased risk of periodontitis but positively related to elevated antibody levels against periodontopathogens. For an unhealthy plant-based diet, the opposite trends were observed.