Elevated Antibody Levels Research Articles

Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report

BackgroundHINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia.Case presentationA 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up.ConclusionsConcurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology.

Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated P. gingivalis peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from P. gingivalis (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined. B cells from inflamed gingival tissue were single-cell sorted, and immunoglobulin (Ig) genes were amplified, sequenced, cloned and expressed (n=63) as recombinant monoclonal antibodies, and assayed for citrulline-reactivities by enzyme-linked immunosorbent assay. Additionally, affinity-purified polyclonal anti-cyclic-citrullinated peptide (CCP2) IgG, and monoclonal antibodies derived from RA blood and synovial fluid B cells (n=175), were screened for CPP3-reactivity. Elevated anti-CPP3 antibody levels were detected in RA (11%), mainly CCP2+ RA, compared to controls (2%), p<0.0001, with a significant association to HLA-DRB1 shared epitope alleles, smoking and baseline pain, but with low correlation to autoimmune ACPA fine-specificities. Monoclonal antibodies derived from gingival B cells showed cross-reactivity between P. gingivalis CPP3 and human citrullinated peptides, and a CPP3+/CCP2+ clone, derived from an RA blood memory B cell, was identified. Our data support the possibility that immunity to P. gingivalis derived citrullinated antigens, triggered in the inflamed gum mucosa, may contribute to the presence of ACPA in RA patients, through mechanisms of molecular mimicry.

GluR3B Antibody Was a Biomarker for Drug-Resistant Epilepsy in Patients With Focal to Bilateral Tonic-Clonic Seizures.

Considering the role of GluR3B antibody-mediated excitotoxicity in the progression of epilepsy, the purpose of this study was to evaluate the clinical significance of GluR3B antibody level as a novel biomarker for the prognosis of unknown etiology drug-resistant epilepsy (DRE) in patients with focal to bilateral tonic-clonic seizures. The study included 193 patients with focal to bilateral tonic-clonic seizures in the modeling cohort. Serum and CSF samples from patients were collected, and GluR3B antibody levels were detected by an ELISA kit. Serum and CSF GluR3B antibody levels in patients with DRE were significantly increased compared with those in patients with drug-responsive epilepsy. Univariate logistic regression analysis underlined that patients with high GluR3B antibody levels had a significantly increased risk of developing DRE. A logistic regression model demonstrated that increased GluR3B antibody levels were an independent factor in predicting DRE. External verification showed that the model constructed for the prediction of DRE had good adaptability. Finally, decision curve analysis highlighted the superior clinical net benefit in DRE prognosis by GluR3B antibody level. In summary, elevated levels of GluR3B antibody are an early biomarker to predict the prognosis of DRE; in addition, targeting GluR3B antibody may be a promising treatment strategy for patients with DRE.

Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies.

The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BackgroundThe inactivated Sinopharm/BBIBP COVID‐19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low‐ and middle‐income nations due to their low storage requirements.ObjectiveThis study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster.MethodsA total of 353 healthy adult participants, aged 20–74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine‐induced virus‐specific antibody levels (SARS‐CoV‐2‐IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points.ResultsNeutralizing titers induced by the two doses of inactivated vaccine for COVID‐19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster.ConclusionBy monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer

BackgroundIn patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits.MethodsIn this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization.ResultsAmong 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of −0.3 percentage points (two-sided 90% CI, −2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported.ConclusionsIn patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.)

Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity.

Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.

Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.

Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host’s immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.

Persistence of Anti-SARS-CoV-2 Antibodies in Long Term Care Residents Over Seven Months After Two COVID-19 Outbreaks.

BackgroundAs part of the public health outbreak investigations, serological surveys were carried out following two COVID-19 outbreaks in April 2020 and October 2020 in one long term care facility (LTCF) in British Columbia, Canada. This study describes the serostatus of the LTCF residents and monitors changes in their humoral response to SARS-CoV-2 and other human coronaviruses (HCoV) over seven months.MethodsA total of 132 serum samples were collected from all 106 consenting residents (aged 54-102) post-first outbreak (N=87) and post-second outbreak (N=45) in one LTCF; 26/106 participants provided their serum following both COVID-19 outbreaks, permitting longitudinal comparisons between surveys. Health-Canada approved commercial serologic tests and a pan-coronavirus multiplexed immunoassay were used to evaluate antibody levels against the spike protein, nucleocapsid, and receptor binding domain (RBD) of SARS-CoV-2, as well as the spike proteins of HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43. Statistical analyses were performed to describe the humoral response to SARS-CoV-2 among residents longitudinally.FindingsSurvey findings demonstrated that among the 26 individuals that participated in both surveys, all 10 individuals seropositive after the first outbreak continued to be seropositive following the second outbreak, with no reinfections identified among them. SARS-CoV-2 attack rate in the second outbreak was lower (28.6%) than in the first outbreak (40.2%), though not statistically significant (P>0.05). Gradual waning of anti-nucleocapsid antibodies to SARS-CoV-2 was observed on commercial (median Δ=-3.7, P=0.0098) and multiplexed immunoassay (median Δ=-169579, P=0.014) platforms; however, anti-spike and anti-receptor binding domain (RBD) antibodies did not exhibit a statistically significant decline over 7 months. Elevated antibody levels for beta-HCoVs OC43 (P<0.0001) and HKU1 (P=0.0027) were observed among individuals seropositive for SARS-CoV-2 compared to seronegative individuals.ConclusionOur study utilized well-validated serological platforms to demonstrate that humoral responses to SARS-CoV-2 persisted for at least 7 months. Elevated OC43 and HKU1 antibodies among SARS-CoV-2 seropositive individuals may be attributed to cross reaction and/or boosting of humoral response.

Subcutaneous parasitic infection in Slovenia: a case report

Filariasis is a parasitic disease caused by infection with roundworms of the Filarioidea superfamily. Depending on the species of roundworm, the disease can present itself in one of three forms. It can affect the lymphatic system, the subcutaneous tissue, or serous cavities. We present the case of a male patient from central Europe with a subcutaneous manifestation similar to filariasis. Laboratory findings showed eosinophilia and elevated levels of IgE antibodies, and histological examination of skin biopsy material showed granulation tissue with lymphoid and plasma cell infiltration. When the lesion was examined under a microscope following an excision, live wormlike parasites about 3.5 cm long were detected. Such parasitic infections are usually encountered in tropical regions and sometimes reported in travelers returning from endemic countries. Our patient, however, had never left Europe, which is what makes this case so interesting.

Ispitivanje povezanosti između vrste i titra antifosfolipidnih antitela sa kliničkim manifestacijama antifosfolipidnog sindroma

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by arterial or venous thromboses and/or spontaneous abortions associated with a persistently elevated level of antiphospholipid antibodies. To date, no clear relationship has been established between levels and types of autoimmune antibodies and clinical manifestations of APS, which can range from mild coagulation disorders to life-threatening conditions. Aim: The aim of this study is to examine the relation between antiphospholipid antibody type and titer and the most common clinical manifestations of APS. Materials and methods: The retrospective study included 32 patients with a confirmed laboratory finding of elevated antiphospholipid antibodies, who came for follow-up examinations to the Hemophilia Unit of the University Clinical Center of Serbia, between June 1, 2017 and December 31, 2018. Data on patients were taken from their medical records. Basic demographic data, type and titer of antiphospholipid antibodies, and their association with the present clinical manifestations of APS were analyzed using standard statistical methods. Results: There was no significant difference regarding the frequency of positive results for lupus anticoagulant, anti-cardiolipin, and anti-beta-2-GP-I antibodies, between the symptomatic and asymptomatic group. The percentage of persons with simultaneous positivity for two or all three antiphospholipid antibodies was the same in both groups of subjects. Conclusion: As opposed to previous studies, our study did not demonstrate a correlation between the titer of antiphospholipid antibodies and the clinical manifestations of APS. Symptomatic and asymptomatic patients did not significantly differ in the frequency of elevated antibodies. These results indicate that the presence of other factors, which are as yet little-known, is necessary for the clinical manifestations of APS.

Lymphocytic Thyroiditis- Association between Cytology and Biochemical Findings

Introduction: Hashimoto’s thyroiditis otherwise called as chronic lymphocytic thyroiditis is the most common cause of hypothyroidism and one of the most common thyroid lesions in Fine Needle Aspiration Cytology (FNAC). Diagnosis depends on clinical findings, ultrasonographic findings, thyroid profile and antithyroid antibody levels along with the FNAC findings. Not much studies are there which have assessed the association of the clinical and biochemical parameters with the cytological findings. Aim: To grade the cytological features of lymphocytic thyroiditis and to study the association of the grades with Thyroid Function Test (TFT) and antithyroid antibody levels. Materials and Methods: A prospective time bound analytical observational study of one year was carried out in the Department of Pathology at Government Medical College, Palakkad, Kerala, India after obtaining approval from the Institutional Ethics Committee (IEC). Out of the total of 462 cases of thyroid lesions who underwent Fine Needle Aspiration (FNA), 147 cases were lymphocytic thyroiditis as per cytology. Of these, 40 cases had Thyroid Stimulating Hormone (TSH), Antithyroglobulin Antibody (ATG) and Antithyroid Peroxidase Antibody (ATPO) levels known which were included in the study. Cytological grading of those were done and the association of the same with the above mentioned parameters was studied. Data was analysed using Statistical Package for the Social Sciences (SPSS) software. Descriptive statistics were calculated and presented as percentages, mean and Standard Deviation (SD). Chi-square test was used to find the association between the categorical variables. The p-value &lt;0.05 was taken as statistically significant. Results: Cytomorphology was diagnostic of thyroiditis in all the cases. Out of the 40 cases, 32 were females.The most common age group affected was 31-40 years, though it ranged from 18-68 years. Most common clinical presentation was diffusely enlarged thyroid, though a few presented as nodular disease. Most of the patients had grade 1 thyroiditis (23 cases) followed by grade 2 (13 cases). Elevated antithyroid antibody levels - ATPO elevated in 32 cases and ATG in 20 cases. TSH was seen elevated in 28 cases of thyroiditis. No association was observed with the antithyroid antibody levels and the cytological grade. Conclusion: Lymphocytic infiltration into the follicles is the diagnostic cytological feature of chronic lymphocytic thyroiditis. TSH elevation and positive ATPO levels strongly suggest Hashimoto’s thyroiditis. No association was found between the cytological grade and TSH and antibody levels.

Non-SARS Coronaviruses in Individuals with Psychiatric Disorders.

The pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has highlighted the importance of coronaviruses in human health. Several seasonal, non-SARS Coronaviruses are endemic in most areas of the world. In a previous study, we found that the level of antibodies to these seasonal Coronaviruses was elevated in persons with a recent onset of psychosis. In the current study, the level of antibodies to seasonal Coronaviruses was compared between individuals with psychiatric disorders and a non-psychiatric comparison group. Participants (N=195) were persons with a diagnosis of schizophrenia, bipolar disorder, major depressive disorder, or without a psychiatric disorder. Each participant had a blood sample drawn from which were measured IgG antibodies to the spike proteins in four non-SARS Coronaviruses, 229E, HKU1, NL63, and OC43, using a multiplex electrochemiluminescence assay. Linear regression models were employed to compare the levels of antibodies between each psychiatric group and the comparison group adjusting for demographic variables. Logistic regression models were employed to calculate the odds ratios associated with increased levels of antibodies to each seasonal Coronavirus based on the 50th percentile level of the comparison group. The schizophrenia group had significantly increased levels of antibodies to the seasonal Coronaviruses OC43 and NL63. This group also had increased odds of having elevated antibody levels to OC43. The major depression group showed a significantly lower level of antibodies to Coronavirus 229E. There were no significant differences between any of the psychiatric groups and the comparison group in the levels of antibodies to seasonal Coronaviruses 229E or HKU1. The elevated level of antibodies to OC43 and NL63 in the schizophrenia group indicates increased exposure to these agents and raises the possibility that Coronaviruses may contribute to the etiopathology of this disorder. The cause-and-effect relationship between seasonal Coronaviruses and psychiatric disorders should be the subject of additional investigations focusing on longitudinal cohort studies.

Establishment of a Hyperacute Rejection Model of ABO-Incompatible Renal Transplantation in Nonhuman Primates.

The establishment of a hyperacute rejection (HAR) model of ABO-incompatible kidney transplantation (ABOi-KTx) in nonhuman primates is of great significance for the study of the relevant clinical pathophysiological processes and related interventions in ABOi-KTx. In this study, blood group B cynomolgus monkeys were presensitized with synthetic blood group A-antigen conjugated to keyhole limpet hemocyanin (A-KLH) to boost circulating anti-A antibody levels. The serum anti-A antibody levels were measured by flow cytometry using type A human reagent red blood cells (RBCs) or monkey primary renal tubular epithelial cells (RTECs) as target cells. ABOi-KTx was performed in type B monkeys using type A monkeys as donors. After 14 days of A-KLH sensitization, 12 of 16 (75%) type B monkeys had significantly elevated anti-A antibody levels. We found that in order to avoid irregular results in the detection of blood group antibodies by flow cytometry, it was more effective to use RTECs rather than RBCs as target cells. In the absence of presensitization, ABOi-KTx in three monkeys with relatively high levels of natural anti-A antibodies did not produce HAR. However, when four Type B monkeys with significantly increased anti-A antibodies after presensitization were randomly selected as recipients for ABOi-KTx, the allografts in all four monkeys developed HAR with typical pathologic characteristics. Thus, we have successfully established a monkey model of HAR in ABOi-KTx via blood group antigen presensitization, which will be helpful for the further study of rejection, accommodation, and clinical intervention in ABOi-KTx.

740 A case of acute Campylobacter COLI myocarditis post-mRNA anti-SARS-CoV-2 vaccine. Was vaccination an innocent bystander or a determining factor?

A 24-year-old healthy man, smoker (2 pack-years), was admitted to the Cardiology Unit for chest pain and fever occurred 2 days after anti-SARS-CoV-2 vaccination. There were no pathological findings at physical examination. The electrocardiogram showed diffuse ST elevation. Laboratory tests showed a significant increment of Troponin I levels (4697 ng/l → 6236 ng/l after 3 h), White Blood Cells (17 610/mmc) and C-Reactive Protein (8.36 mg/dl). Echocardiography showed normal left ventricular systolic function with no evidence of pericarditis. These findings were consistent with a probable case of acute myocarditis. Cardiac magnetic imaging demonstrated myocardial oedema of the posterior wall of the left ventricle at T2-weighted images, with patchy areas of subepicardial late gadolinium enhancement. Based on Centers for Disease Control and Prevention myocarditis diagnostic criteria, a diagnosis of acute myocarditis was made and treatment with Non-Steroidal Anti-Inflammatory Drugs was started. Regarding etiology agent determination, in the COVID19 era, the first suspect was anti-SARS-CoV-2 mRNA-vaccine-induced myocarditis. Several case series and analyses of a large national health care organization database helped to identify features linked to these types of myocarditis. The highest incidence was observed among male juvenile subjects, usually 48–72 h after the second dose of vaccination, with elevated levels of spike antibody for SARS-CoV-2. Nevertheless, in the presented clinical case, the patient had received the first dose of BNT162b2 vaccination two days before hospital admission and showed negative serology tests for SARS-CoV-2. In recent medical history, two days before the onset of fever and chest pain, the patient had episodes of diarrhea which persisted during the first week of hospitalization. All immunological and microbiological tests result negative, except for a stool culture positive for Campylobacter coli. Interestingly a revision of literature showed several cases of myocarditis linked to Campylobacter species. In particular, of 13 reported cases, 12 (92%) were male with a mean age of 26 ± 8.8 years, and cardiac symptoms present generally 2–4 days after diarrhea. In this particular setting, the first and more obvious hypothesis was strongly questioned because of an unexpected finding in the stool culture. In fact, Campylobacter spp. related myocarditis is an extremely rare condition, even if this pathogen is associated with important immunological interferences, as shown by its relationship with the Guillain-Barre syndrome. Further, myocarditis related to mRNA anti-SARS-CoV-2 vaccine is considered a rare complication. We hypothesized that the association of the two components could have acted synergistically to produce an immune system activation against cardiac muscle. Additional investigations are required to clarify the link between vaccination and possible improper immune response. In conclusion, this case represents a typical example in which the cause of the disease should be well investigated because the initial etiological theory is not definitive, especially in the SARS-CoV-2 era.

Transitional elevation of anti-tissue transglutaminase antibodies in children with type 1 diabetes mellitus without coeliac disease

The frequent association of type 1 diabetes mellitus with coeliac disease is well known. Development of transitional elevation of anti-tissue transglutaminase antibodies in the diagnosis of type 1 diabetes is reported in some studies. In these cases, the anti-tissue transglutaminase antibodies returned to normal without gluten-free diet. Our aim was to assess the frequency of transitional elevation of anti-tissue transglutaminase in our type 1 diabetes patients. We aimed to investigate the prevalence of coeliac disease in patients with type 1 diabetes. Patients with type 1 diabetes at the Ist Department of Paediatrics, Semmelweis University, were enrolled in the study (238 girls, 265 boys; the median age at the time of type 1 diabetes diagnosis was 7.83 [4.67-11] years). Descriptive statistical analysis was done and the time of appearance, extent, frequency and type of elevated anti-tissue transglutaminase antibodies were examined. The proportion of children with diagnosed coeliac disease was 12.52%. We detected transitional anti-tissue transglutaminase elevation in 48 cases (10.9%). Temporarily elevated antibody levels were measured 71 times. In 34 children (70.83%), the temporary elevation occured once, while in the others, antibody levels became positive 2-8 times. The elevation of the IgA antibody was more frequent than the elevation of the IgG antibody (54 vs. 5). The frequency of temporary elevated anti-tissue transglutaminase levels is considered high. Our study confirms the recommendation that in the case of moderate anti-tissue transglutaminase levels with lack of clinical symptoms, control antibody measurement is necessary with ongoing gluten consumption. Orv Hetil. 2021; 162(48): 1924-1930.

Effects of animal protein intake during pregnancy on autoimmune thyroiditis in pregnant women with mild iodine deficiency.

Iodine and animal protein may affect thyroid function. In the present study, we explored the association between animal protein intake and thyroid antibody status in pregnant women following universal salt iodisation. Pregnant women were enrolled using a multistage, stratified random sampling method in Shanghai. In total, 4646 eligible women were interviewed in person. We used a validated food frequency questionnaire and food composition tables to calculate the daily intakes of protein and iodine. We collected urine samples and performed thyroid antibody tests. Positive thyrotropin receptor antibody (TR-Ab) rates were different among animal protein intake groups (p < 0.05). Median urinary iodine concentration (UIC) was higher in the thyroid peroxidase antibody (TPO-Ab) positive group than in the negative group (p < 0.05). The median of total protein intake, animal protein intake and UIC was higher in the TR-Ab positive group than in the negative group (p < 0.05). The median of total protein intake and UIC was higher in the TPO-Ab/TG-Ab/TR-Ab positive group than in the negative group (p < 0.05). Multivariable logistic regression results showed that insufficient iodine had a negative correlation with positive TPO-Ab and positive TR-Ab (p < 0.05). The middle third and top third animal protein intakes served as protective factors for TR-Ab (coefficient = 0.559, 95% confidence interval [CI] = 0.415-0.752, p < 0.001; coefficient = 0.0.406, 95% CI = 0.266-0.621, p < 0.001) and positive TPO-Ab/TR-Ab/TG-Ab (coefficient = 0.817, 95% CI = 0.687-0.971, p = 0.022; coefficient = 0.805, 95% CI = 0.672-0.964, p = 0.018). Adequate animal protein intake protects against elevated anti-thyroid antibody levels in pregnant women with mild iodine deficiency.

Facial nerve paresis in the course of masked mastoiditis as a revelator of GPA

PurposeThe aim of this study was to present a series of 6 patients with facial nerve palsy and masked mastoiditis which constituted as revelators of localized granulomatosis with polyangiitis (GPA) and to evaluate the utility of the ACR/EULAR 2017 provisional classification criteria for GPA in such cases.MethodsStudy group included 58 patients with GPA. Cases with facial nerve palsy and masked mastoiditis were thoroughly analyzed.ResultsThe mean age of patients was 37 years. All manifested unilateral facial nerve palsy and hearing loss, while only 2 reported aural complaints suggesting inflammatory cause of the disease. All cases were qualified for surgical intervention. Intraoperative findings were similar: granulation tissue in tympanic cavity and/or pneumatic spaces of the mastoid process. Only 50% of histopathological results suggested vasculitis. In all cases, elevated levels of antineutrophil cytoplasmic antibodies (ANCA) against peroxidase 3 (PR3-ANCA) were determined. Two patients presented rapid progression of the disease and died within 1 week and 2 months, respectively. Four other patients manifested gradual improvement of hearing and facial nerve function after treatment.ConclusionGPA should be included into differential diagnosis in all cases of persistent facial nerve palsy especially when otological symptoms coexist. Even localized GPA could be very aggressive, revelating generalized form of the disease. Rapid systemic treatment of GPA can protect hearing and facial nerve from permanent severe dysfunction. The ACR/EULAR 2017 provisional classification criteria for GPA seem to be valuable tool in diagnosing ENT patients with localized otological form of the disease.

Clinical portrait of a patient with COVID-19. The experience of a multidisciplinary clinic

Evaluation of the clinical characteristics in patients with COVID-19. The article presents clinical and instrumental data of 1169 patients included in a single-center mixed study. Patients were tested for COVID-19 using polymerase chain reaction, computed tomography (CT), and antibody screening. Clinical history data were collected. In patients with confirmed COVID-19, lung damage and a positive test for antibodies were observed in 75.5 and 45.2% of cases, respectively. The most common symptoms of COVID-19 were: fever (73.2%), weakness, (72.7%) dry cough (62.8%) and shortness of breath (55.4%). Patients with CT-visualized lung lesions were more likely to have clinical symptoms and elevated levels of antibodies. Patients with chronic diseases of the endocrine system, circulatory system, and respiratory system had a more severe course of the disease (CT-14: 91.296.3%) than patients without chronic diseases (CT-14: 85,1%). We have compiled a clinical profile of patients with COVID-19 and highlighted the most significant clinical characteristics corresponding to a more severe course of the disease. Our data showed that patients with chronic diseases require a personalized approach and the development of specific criteria for the diagnosis and treatment of COVID-19.