Expression of Gn protein of severe fever with thrombocytopenia syndrome virus and its immunogenicity / 中国生物制品学杂志

@#Objective To express the Gn protein of severe fever with thrombocytopenia syndrome virus(SFTSV) through adeno-associated virus 9(AAV9) expression system and evaluate its immunogenicity.Methods SFTSV Gn gene was inserted into viral vector pAAV-CMV-FH and the recombinant plasmid was transfected into HEK293T cells to obtain recombinant virus AAV9-Gn.The expression of Gn protein was determined by immunofluorescence and Western blot.Eighteen fernale BALB/c mice were randomly divided into three groups:Mock group(serum-free DMEM),AAV9-GFP group(1 × 10~(11) vg) and AAV9-Gn group(1 × 10~(11) vg),all of which were injected intramuscularly into the right hind limb at a dose of 100 μL per mouse.The body mass,diet,behavior and mental state of mice in each group were monitored continuously for 21 d,and the change rate of body mass was calculated;At 2,4,8 and 16 weeks after immunization,the levels of SFTSV neutralizing antibody in serum of mice in each group were detected by fluorescent reduction neutralization test(FRNT),and the levels of specific IgGl and IgG2a in serum of mice in AAV9-Gn group were detected by ELISA.Results After incubation with specific antibody,Vero cells transfected with AAV9-Gn showed specific green fluorescence under fluorescence microscope,and had specific binding to mouse anti-SFTSV Gn monoclonal antibody,and the specific binding bands were found at a relative molecular mass of about 61 000.The body mass of the three groups showed an increasing trend,there was no significant difference between the three groups(F=0.158—2.621,P> 0.05),and the diet,behavior and mental state were normal.At 2,4,8 and 16 weeks after immunization,the titer of SFTSV neutralizing antibody in serum of mice in AAV9-Gn group was significantly higher than that of Mock group and AAV9-GFP group(H=13.332—14.538,each P <0.001),and the titer peak appeared at 8 weeks;The level of specific IgG1 in serum of mice was significantly higher than that of IgG2a(F=4.373—12.975,each P <0.05) at different time points.Conclusion SFTSV Gn protein can be expressed correctly through AAV9 expression system,and has low toxicity to mice with good immunogenicity,which is expected to be a candidate component of SFTSV vaccine.

Immunogenicity evaluation of prototype and variant inactivated SARS-CoV-2 vaccines in rats / 中国生物制品学杂志

@#Objective To evaluate the immunogenicity of prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines in rats.Methods Five female Wistar rats were immunized with SARS-CoV-2 inactivated vaccines of prototype,Beta,Gamma and Delta strains through thigh muscle twice at an interval of 14 d,with an immunization dose of 3 μg virus protein/(0.5 mL per rat).Serum samples were collected and isolated by vein 14,28 and 42 d after the first immunization.The serum IgG antibody levels were detected by indirect ELISA,the titers of serum neutralizing antibody were measured by microneutralization,and the antigenic ratios of the serum neutralizing antibody titers were calculated to evaluate the antigenicity difference between different strains.Results at 14 d after the first immunization,IgG antibodies against four strains of virus were detected in all immunized serum samples.The levels of IgG antibodies increased by more than 10 times at 28 d compared with those at 14 d,and decreased slightly at 42 d.At 14 d after the first immunization,all the neutralizing antibodies against the four strains were positive in the serum of rats immunized with prototype strain or Delta strain vaccine;In the serum samples of rats immunized with Beta and Gamma strains,all the neutralizing antibodies against Beta and Gamma strains were positive,while some neutralizing antibodies against prototype or Delta strains were positive.At 28 d after the first immunization,the neutralizing antibodies in the immune serum of the four strains were positive,and the titers of neutralizing antibodies were significantly higher than those at 14 d;The neutralizing antibody titers were slightly lower at 42 d after the first immunization than 28 d.There was small difference in the antigenicity between Beta and Gamma,prototype and Gamma,but significant difference in the antigenicity between prototype and Beta strains.Conclusion The prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines can stimulate rats to produce neutralizing antibodies with high titer,while the immunogenicity has difference.

Pseudotumor inflamatorioocular asociado a IgG4. Reporte de un caso / IgG4-Associated Ocular Inflammatory Pseudotumor. A Case Report

Resumen Introducción: El pseudotumor inflamatorio ocular asociado a IgG4 es un proceso inflamatorio no neoplásico y poco frecuente con una incidencia de 0.28-1.08 por cada 100,000 personas. El diagnóstico de esta patología es de exclusión debiendo cumplir criterios histopatológicos, agrandamiento de un órgano en específico y concentraciones serias de IgG4. El tratamiento tiene como objetivo evitar las complicaciones secundarias. Caso clínico: Mujer de 54 años de edad sin patologías previas referidas, acude refiriendo que 6 meses previos presenta de forma súbita y sin causa aparente prurito a nivel de globo ocular y párpado izquierdo, además de disminución de la agudeza visual y dolor retroocular, motivo por el que acude a valoración. Al examen físico presentó movimientos oculares normales, proptosis izquierda, dolor a la palpación, hiperemia subconjuntival, opacidad corneal, ausencia de reflejo rojo y más renitente a la presión el ojo izquierdo en relación con el contralateral. Tomografía cráneo-toraco-abdominal reporta a nivel ocular izquierdo imágenes sugestivas de melanoma coroideo sin hallazgos de actividad metastásica. Se realiza enucleación de ojo izquierdo. Se envía pieza a patología la cual reporta infiltrado difuso linfoplasmocítico positivas para IgG4. Conclusión: La enfermedad por IgG4 ocular es una patología muy infrecuente de clínica inespecífica y diagnóstico complejo. Sin embargo, un abordaje rápido y correcto es fundamental para evitar complicaciones.

Abstract Introduction: IgG4-associated ocular inflammatory pseudotumor is a rare, non-neoplastic inflammatory process with an incidence of 0.28-1.08 per 100,000 people. The diagnosis of this pathology is one of exclusion, having to meet histopathological criteria, enlargement of a specific organ, and serious concentrations of IgG4. Treatment aims to avoid secondary complications. Clinical case: A 54-year-old woman with no previous reported pathologies, reports that for the past 6 months she has itching at the level of the eyeball and the left eyelid, suddenly and without apparent cause, in addition to decreased visual acuity and retro-ocular pain; this is why she asked for the evaluation. The physical examination revealed normal eye movements, left proptosis, pain on palpation, subconjunctival hyperemia, corneal opacity, absence of red reflex, and the left eye being more resistant to pressure in relation to the contralateral eye. The cranio-thoraco-abdominal tomography reported images at the left ocular level that were suggestive of choroidal melanoma without findings of metastatic activity. Enucleation of the left eye was performed. The specimen was sent to pathology which reported diffuse lymphoplasmacytic infiltrate positive for IgG4. Conclusion: Ocular IgG4 disease is a very rare pathology with non-specific symptoms and complex diagnosis. However, a quick and correct approach is essential to avoid complications.

Immunoglobulin G4-Related Disease, A Diagnosis to Take into Account: About a Case

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated and multisystemic condition associated with developing fibroinflammatory lesions in any organ. The diagnosis is made based on the sum of clinical, serological, radiological, and histopathological criteria; however, this is often difficult due to its similarity to neoplasms, infections, or other immune-mediated diseases. Treatment is based on corticosteroids, in a possible combination with immunomodulators. The present case concerns a 59-year-old man with a history of jaundice syndrome and weight loss, admitted for suspected malignant neoplasia of the bile duct. Imaging revealed stricture with dilation of the intrahepatic bile ducts, prominent pancreas, pancreatic duct stricture, and nodular renal lesions. Due to the history of left submandibulectomy two years before the current disease and histology compatible with Küttner's tumor, plus the high IgG4 serum values, the diagnosis of IgG4-RD was established. He started treatment with corticosteroids and was asymptomatic during follow-up.

La enfermedad relacionada con inmunoglobulina G4 (ER-IgG4) es una condición inmunomediada y multisistémica asociada al desarrollo de lesiones fibroinflamatorias en cualquier órgano. El diagnóstico se realiza bajo la suma de criterios clínicos, serológicos, radiológicos e histopatológicos; sin embargo, este suele ser difícil debido a su similitud con neoplasias, infecciones u otras enfermedades inmunomediadas. El tratamiento se basa en corticosteroides, en una posible combinación con inmunomoduladores. El presente caso trata de un varón de 59 años con historia de síndrome ictérico y baja de peso, admitido por sospecha de neoplasia maligna de la vía biliar. Las imágenes revelaron estenosis con dilatación de las vías biliares intrahepáticas, páncreas prominente, estenosis del conducto pancreático y lesiones nodulares renales. Debido al antecedente de submandibulectomía izquierda 2 años antes de la enfermedad actual e histología compatible con tumor de Küttner, más los valores elevados de IgG4 sérico, se estableció el diagnóstico de ER-IgG4. Inició tratamiento con corticosteroides y cursó asintomático durante el seguimiento.

Compromiso oftálmico en enfermedad relacionada con IgG4 / Ophthalmic involvement in IgG4-related disease

Resumen Introducción: la enfermedad oftálmica relacionada con IgG4 (EOR-IgG4) presenta una frecuencia del 11-59%. Pocos estudios describen las disparidades con los pacientes con ER-IgG4 extraoftálmica (NO EOR-IgG4). Objetivos: describir las características clínicas, imagenológicas, anatomopatológicas, resultados de laboratorio y tratamiento de la EOR-IgG4, y compararlas con las de los pacientes NO EOR-IgG4. Materiales y métodos: se realizó un estudio descriptivo sobre una cohorte de 54 pacientes con ER-IgG4. Se reclutaron 16 pacientes con EOR-IgG4 y 38 con NO EOR-IgG4. Se compararon ambos grupos. Resultados: la EOR-IgG4 predominó en mujeres. El 75% presentó afectación oftálmica bilateral. El antecedente de asma se asoció al grupo NO EOR-IgG4 (p=0,018). Los pacientes con EOR-IgG4 presentaron niveles séricos menores de IgE e IgG total, y la glándula lagrimal fue la estructura más afectada. Predominó el infiltrado linfoplasmocitario y eosinofílico, siendo la fibrosis estoriforme más frecuente que la no estoriforme en el grupo EOR-IgG4. Conclusiones: si bien los resultados fueron similares a lo reportado previamente, en discordancia con otras series, encontramos asociación negativa entre el asma y los niveles de IgG total sérica en los pacientes EOR-IgG4.

Abstract Introduction: IgG4-related ophthalmic disease (IgG4-ROD) presents a frequency of 11-58.8%. Few studies describe the disparities with patients with extraophthalmic IgG4-related disease (NOT IgG4-ROD). Objectives: describe the clinical, imaging, pathological characteristics, laboratory results, and treatment of IgG4-ROD characteristics; and compare them with those of the NOT IgG4-ROD patients. Materials and methods: a descriptive study was carried out on a cohort of 54 patients with ER-IgG4. 16 patients with IgG4-ROD and 38 with NOT IgG4-ROD were recruited. The data was analyzed with the SPSS Statistics 19 software. Results: IgG4-ROD predominated in women. 75% presented bilateral ophthalmic involvement. A history of asthma was associated with the NOT IgG4-ROD group (p=0,018). Patients with IgG4-ROD presented lower serum levels of IgE and total IgG, and the lacrimal gland was the most affected structure. Lymphoplasmacytic and eosinophilic infiltrates predominated, with storiform fibrosis being more frequent than non-storiform in the IgG4-ROD group. Conclusions: although the results were similar to those previously reported, in disagreement with other series, we found a negative association between asthma and serum total IgG levels with EOR-IgG4 patients.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (? or ?60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post- omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months

Hypophysitis an uncommon manifestation of IgG4-related disease: Case report

IgG4-related disease is a recently described disease that can involve various organs and systems. Single organ involvement is the exception to the rule, it is generally a multi-system entity. We present a 36-year-old woman, with no previous pathological history or autoimmune disease, with headache caused by cystic macroadenoma. A transsphenoidal resection was performed and pathology documented areas of fibrosis with a predominantly plasmolymphocytic infíltrate and positive IgG4 staining in more than 20 cells per high-power field, meeting diagnostic criteria for IgG4-related sclerosing disease. Involvement of other organs was ruled out, and the patient improved clinically after management.

La enfermedad relacionada con IgG4 es una entidad recientemente descrita, capaz de involucrar diversos órganos y sistemas. El compromiso de órganos aislados es la excepción a la regla, dado que generalmente se trata de una entidad multisistémica. Se presenta el caso de una mujer de 36 años, sin antecedentes patológicos previos, en quien como causa de cefalea se documenta un macroadenoma quístico llevado a resección transesfenoidal, cuyo resultado de patología documenta zonas de fibrosis con infiltrado de predominio plasmo-linfocitario y la tinción para IgG4 positiva en más de 20 células por campo de alto poder, lo que configura criterios diagnósticos para enfermedad esclerosante relacionada con IgG4; se descartó compromiso de otros órganos y hubo mejoría clínica posterior al manejo.

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Enfermedad relacionada con IgG4, enfermedad de Erdheim Chester y compromiso aórtico y/o sus ramas. Diagnóstico diferencial con otras vasculitis de grandes vasos / IgG4 related disease, Erdheim Chester disease and aortic involvement and/or its branches. Differential diagnosis with other large vessel vasculitis

La afección cardiovascular en entidades como Erdheim-Chester (EEC), una rara histiocitosis de células no Langerhans, y la enfermedad relacionada con IgG4 (ER-IgG4), una afección fibrinoinflamatoria inmunomediada, es muy variada y habitualmente asintomática hasta su progresión a daños irreversibles cuando no es sospechada. Ante la dificultad de realizar biopsias por el sitio anatómico, es fundamental valerse de características clínicas, demográficas o imagenológicas que puedan diferenciarlas de otras entidades, como las arteritis de grandes vasos. La población masculina, los mayores de 60 años con compromiso a nivel de la aorta abdominal infrarrenal o aneurismas a nivel de la aorta ascendente con o sin compromiso de otros órganos, son orientativos de ER-IgG4. En la EEC es característico el tejido blando concéntrico que recubre la aorta (aorta recubierta) y sobre todo ante la presencia de fibrosis retroperitoneal, compromiso de huesos largos, hidronefrosis, lesión renal aguda posrrenal e hipertensión arterial, existencia de tejido fibrótico perirrenal, engrosamiento de la fascia renal y tejido adiposo perirrenal (signo del riñón peludo).

Cardiovascular disease in entities such as Erdheim-Chester (ECD), a rare non-Langerhans cell histiocytosis, and IgG4-related disease (ER-IgG4), an immunemediated fibrinoinflammatory disease, is highly varied and usually asymptomatic until it progresses to irreversible damage if they are not taken into account. Given the difficulty of performing biopsies by the anatomical site, it is essential to use clinical, demographic or imaging characteristics that can differentiate them from other entities such as large vessel arteritis. Male population, over 60 years of age with involvement of the infrarenal abdominal aorta or aneurysms at the level of the ascending aorta with or without involvement of other organs, are indicative of ER-IgG4. In ECD, the concentric soft tissue covering the aorta (covered aorta) is characteristic, and especially in the presence of retroperitoneal fibrosis, involvement of long bones, hydronephrosis, post-renal acute kidney injury and arterial hypertension, the presence of perirenal fibrotic tissue, thickening of the renal fascia, perirenal adipose tissue (hairy kidney sign).

Exoftalmos bilateral por compromiso orbitario debido a enfermedad relacionada con IgG4 / Bilateral exophthalmos due to orbital involvement due to IgG4-related disease

La enfermedad relacionada con IgG4 (ER-IgG4) se caracteriza por el compromiso fibrótico e infiltrado linfoplasmocitario con predominio de células IgG4 en uno o varios órganos. El fenotipo limitado a la cabeza y el cuello abarca el compromiso de las glándulas lagrimales y salivares, enfermedad orbitaria, paquimeningitis, hipofisitis, tiroiditis, mastoiditis y compromiso de senos paranasales. Las manifestaciones orbitarias pueden incluir proptosis uni o bilateral, miopatía cicatrizal de los músculos extraoculares, inflamación orbitaria y dolor que pueden simular a la oftalmopatía de Graves. La enfermedad oftálmica relacionada con IgG4 puede presentarse con compromiso de músculos extraoculares y de grasa orbitaria, y usualmente se confunde con afección orbitaria por enfermedad de Graves. Se presenta el caso de un varón de 58 años, con historia de exoftalmos bilateral de más de 15 años de evolución, en quien se arriba al diagnóstico de ER-IgG4 y cuya resonancia magnética de órbitas evidencia un patrón característico de compromiso de músculos extraoculares.

IgG4-related disease (IgG4-ER) is characterized by fibrotic involvement and lymphoplasmacytic infiltrate with IgG4 cells predominance in one or several tissues. The head and neck phenotype includes lacrimal and salivary gland involvement, orbital disease, pachymeningitis, hypophysitis, thyroiditis, mastoiditis, and sinus involvement. Orbital manifestations may include unilateral or bilateral proptosis, extraocular muscles scarring, orbital inflammation, and pain that may mimic Graves' ophthalmopathy. IgG4-related ophthalmic disease may present with extraocular muscles and orbital fat involvement and is often confused with orbital Graves' disease. We present the case of a 58-year-old man, with a history of bilateral exophthalmos of more than 15 years, in whom the diagnosis of IgG4-ER was reached and whose orbits magnetic resonance showed a characteristic pattern of extraocular muscle involvement.

Current insights into Covid-19 vaccination

@#Almost a year after the worldwide appearance of the coronavirus (SARS-CoV-2), several novel vaccines of diverse platforms have been successfully developed and administered. Two mRNA vaccines represented a new type of vaccine that comprised of synthetic mRNA molecules containing the code sequence necessary to build the SARS-CoV-2 spike protein. These mRNA vaccines almost single handedly carried the brunt of the US COVID-19 immunization strategy during the past three years. The known and potential benefits of COVID-19 vaccination outweigh the risks and adverse complications. The ongoing COVID-19 pandemic has stimulated unprecedented research on aspects of the vaccines’ ability to reduce the risk of severe infection and death. Likewise, basic immunological studies are pivotal to unraveling the potential and long-term effects of the vaccines as well as to be able to make adjustments to new vaccine development. As the circulating virus strain continues to evolve, updated vaccines will be critical to protecting the population, particularly the elderly and immune compromised.

A case of duodenal ulcer as prominent manifestation of IgG4-related disease / 北京大学学报(医学版)

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Detection of IgG protein in human urine based on vertical flow paper microfluidic chip / 生物工程学报

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.

Development and verification of an indirect ELISA method for determination of specific IgG antibody against SARS-CoV-2 variant strain in rhesus monkey serum / 中国生物制品学杂志

@#Objective To develop and verify an indirect ELISA method for determination of specific IgG antibody of rhesus monkey serum against SARS-CoV-2 variant strain. Methods An indirect ELISA method for the determination of specific IgG antibody was developed using inactivated SARS-CoV-2 Beta variant strain inactivated vaccine as coating antigen,and optimized for the coating antigen concentration(1,2 and 4 μg/mL),dilution of serum(1∶800～1∶12 800),blocking solution(PBST containing 1% BSA,2% BSA,1% skim milk,2% skim milk and 1% BSA + 1% skim milk),blocking time(30,60 and 90 min),dilution of secondary antibody(1∶5 000,1∶10 000,1∶15 000 and 1∶20 000),incubation time of serum and secondary antibody(30,60 and 90 min),and TMB reaction time(5,10,15,20,25 and 30 min). 60 negative serum samples of rhesus monkeys were detected by the developed method,and the negative and positive critical values were determined. The sensitivity and precision of the methodology were verified. In addition,the specific IgG antibody and neutralizing antibody against SARS-CoV-2 Beta variant strain in 44 serum samples of rhesus monkey were detected by the developed method and microneutralization method,and the correlation and consistency between the two methods were compared. Results The optimum detection conditions were determined:the coating antigen concentration was 1 μg/mL;the blocking solution was PBST containing 1% skim milk,and the blocking time was 30 min;the serum samples to be tested were diluted to 1∶1 600 and incubated for 90 min,and the secondary antibody was diluted to 1∶10 000 and incubated for 30 min;the color development time of substrate was 25 min. The positive critical value and negative critical value of the method was 0. 093 and 0. 084 respectively,and the detection values between them were judged as suspicious. The dilution of5 positive serum samples that showed positive results was 1∶51 200;the coefficients of variation(CVs)of precision were all less than 15%. There was a strong correlation between IgG antibody titer and neutralizing antibody level in the 44 rhesus monkey serum samples(r = 0. 858 0,P < 0. 000 1);the total coincidence rate of the two methods was 90. 9%,the positive coincidence rate was 93. 6%,and the negative coincidence rate was 84. 6%;the consistency test Kappa value was 0. 783 8(95% CI:0. 586 5～0. 981 0). Conclusion The developed indirect ELISA method for eletermination of specific IgG antibody against SARS-CoV-2 Beta variant strain in rhesus monkey serum has good sensitivity and precision,and has strong consistency with microneutralization method,which can be used for the determination of IgG antibody in rhesus monkey serum.

Optimization,verification and application of ELISA method for quantitative detection of varicella-zoster virus IgG antibody / 中国生物制品学杂志

@#Objective To optimize and verify the ELISA method for quantitative detection of varicella-zoster virus(VZV)IgG antibody potency,and use it for the screening of plasma with high potency VZV-IgG in healthy donors.Methods The VZV-IgG indirect ELISA kit from Institut VirionSerion GmbH was selected,the first international standard for varicellazoster immunoglobulin(NIBSC code:W1044)was diluted to 2 IU/mL as the standard,and 4-parameter fitting curve was used to develop the quantitative ELISA method. The method was determined for the optimal linear range and verified for the precision and accuracy. VZV-IgG antibody potency of 1 962 human plasma samples and some batches of human immunoglobulin preparations from 10 plasma stations under Sinopharm Wuhan Plasma-derived Biotherapies Co.,Ltd.(SWPB)were detected by the developed method.Results The linear range of the standard curve was 16. 25 ～ 2 000 mIU/mL,the CV values of precision in intra-and inter-assays were 1. 3% ～ 10. 6% and 4. 270% ～ 7. 636%,and the accuracy in intra-and inter-assays were 92. 30% ～ 111. 02% and 98. 40% ～ 104. 88%,respectively;Sample-adding experiment showed that the measured value of the added sample was 95. 79% ～ 111. 03% of the theoretical value. The positive rate of 1 962 human plasma samples was 94. 29%,and the samples with potency greater than 3 000 mIU/mL accounted for 1. 02%. The potency of VZV-IgG antibody in different kinds of human immunoglobulin preparations was lower,while higher than that of intravenous human immunoglobulin(pH 4).Conclusion The optimized VZV-IgG quantitative detection method can be used for the screening of VZV-IgG in healthy people. The positive rate of VZV-IgG antibody in naturally infected healthy plasma donors is high,while the potency is low,thus,vaccine immunization is required to obtain qualified plasma with high potency.

Clinical value of 1, 3-β-D glucan and mannan IgM/IgG antibodies in the early diagnosis of invasive candidiasis / 中华微生物学和免疫学杂志

Objective:To evaluate the diagnostic value of 1, 3-β-D glucan (BDG), mannan IgM antibody (Mn-IgM) and mannan IgG antibody (Mn-IgG) in invasive candidiasis and to compare the differences in the diagnostic capability of serological markers used alone or in combination.Methods:Serum samples of 126 patients with invasive candidiasis and 104 healthy people who took physical examination during the same period were collected. BDG was detected by dynamic chromogenic method, and Mn-IgM and Mn-IgG were detected by ELISA. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, coincidence rate and Kappa value of the three serological markers used alone or in combination in the diagnosis of invasive candidiasis were analyzed and compared. The receiver operating characteristic (ROC) curves were drawn and the areas under the curves (AUCs) were calculated.Results:The levels of BDG, Mn-IgM and Mn-IgG in patients with invasive candidiasis were significantly higher than those in healthy people ( P<0.01). The sensitivity, specificity, Kappa value and AUC of BDG were 48.41%, 92.31%, 0.389 and 0.842. The sensitivity, specificity, Kappa value and AUC of Mn-IgM were 64.29%, 91.35%, 0.540 and 0.829. The sensitivity, specificity, Kappa value and AUC of Mn-IgG were 27.78%, 95.19%, 0.214 and 0.737. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM were 76.19%, 88.46%, 0.637 and 0.921. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgG were 59.52%, 91.35%, 0.491 and 0.856. The sensitivity, specificity, Kappa value and AUC of Mn-IgM+ Mn-IgG were 69.84%, 90.38%, 0.588 and 0.891. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM+ Mn-IgG were 80.16%, 88.46%, 0.679 and 0.922. Conclusions:The sensitivity of Mn-IgM was higher than that of BDG and Mn-IgG in the diagnosis of invasive candidiasis. When the serological biomarkers were used in combination, BDG+ Mn-IgM and BDG+ Mn-IgM+ Mn-IgG had relatively high Kappa value and AUC, showing high accuracy. The clinical diagnostic value of multiple serological biomarkers used in combination was significantly higher than that of any serological biomarkers used alone. Early combined detection and continuous monitoring of multiple serological biomarkers in patients with high risk of invasive candidiasis could be used clinically to adjust antifungal treatment strategies timely.

IgG4-related hypertrophic pachymeningitis: a case report / 中华神经科杂志

A case of IgG4-related hypertrophic pachymeningitis was reported. The patient was an elderly female, with the course of disease more than 8 years. Clinical manifestations included recurrent headache, vision and hearing loss, exophthalmos and thyroid dysfunction. Finally, she was diagnosed as IgG4-related disease and IgG4-related hypertrophic pachymeningitis by PET-CT and dural biopsy. After treatment with methylprednisolone and mycophenolate mofetil, the patient′s clinical symptoms improved.

Anti-myelin oligodendrocyte glycoprotein-IgG associated disorders coexisting with brucellosis: a case report and literature review / 中华神经科杂志

Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.

Correlation between food-specific IgG antibodies and phenotypes of chronic spontaneous urticaria / 中华皮肤科杂志

Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.