Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child.We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based approaches.Therefore,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary surgery.CASE SUMMARY The patient suffered from epigastric pain for several days.Panendoscopy and computed tomography scan revealed a submucosal tumor.Differential diagnoses included GIST,leiomyoma,teratoma,and mucinous adenocarcinoma.However,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease.CONCLUSION We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

Pulmonary and Orbital Bifocal IgG4 Disease: Case Report and Literature Review

Introduction: IgG4 disease is an orphan, fibro-inflammatory autoimmune disease of recent discovery whose thoracic involvement is rarer. We report a case of Pulmonary and orbital bifocal IgG4 disease with a review of the literature. Observation: This is a 71-year-old patient with a history of hypertension, dyslipidemia, smoking cessation at 15 PA, with progressive dyspnoea, weight loss of 4 kg with PS = 0 for 2 months. The thoracic CT scan revealed 3 pseudotumoral lung lesions of the LIG, LID and LM. The histology of the two CT-guided lung biopsies and the LIG wedge had objectified inflammatory lesions without signs of malignancy. The evolution was marked by the occurrence of a right orbital edema. The cerebral scanner found a voluminous right orbital inflammatory pseudotumor. Biopsy with histology found fibroinflammatory lesions with lymphoplasmacytic infiltrates and positive immunolabeling with anti-IgG4 antibodies. The PET scanner had objectified pulmonary and pleural parenchymal consolidations and moderately hypermetabolic mediastinal ADP with max SUV between 3 and 6. The patient was put on corticosteroid therapy with a favorable outcome. Conclusion: IgG4 disease is rare and difficult to diagnose despite well-defined and consensual diagnostic criteria and classification. The discovery of new biomarkers facilitates the diagnosis and monitoring of patients. Well-codified corticosteroid therapy is effective but possibility of recurrence. The current challenge remains the lack of data on the follow-up of these patients to assess the risk of neoplasia (lymphoma).

A Case of Warthin’s Tumor Together with IgG4-Related Sialadenitis

Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.

IgG4-related kidney disease complicated with retroperitoneal fibrosis:A case report

BACKGROUND IgG4-related disease(IgG4-RD)is a chronic fibrotic disease mediated by immunity recognized by clinicians in recent years.When the kidney is involved,it is called IgG4-related kidney disease(IgG4-RKD).IgG4-related tubulointerstitial nephritis(IgG4-TIN)is a representative manifestation of IgG4-RKD.IgG4-TIN can cause obstructive nephropathy complicated by retroperitoneal fibrosis(RPF).Cases of IgG4-TIN complicated with RPF are rare.Glucocorticoids are the firstline therapeutic medication for IgG4-RD and can significantly improve renal function.CASE SUMMARY Herein,we report the case of a 56-year-old man with IgG4-RKD complicated with RPF.The patient presented to the hospital with complaints of elevated serum creatinine(Cr),nausea,and vomiting.During hospitalization,Cr was 1448.6μmol/L,and serum IgG4 was increased.A total abdominal computed tomography(CT)scan and enhanced CT scan obviously indicated RPF.Although this patient had a long course and renal insufficiency,we performed a kidney biopsy.Renal biopsy showed that the renal tubulointerstitium had focal plasma cell infiltration and increased lymphocyte infiltration accompanied by fibrosis.After combining the biopsy results with immunohistochemistry,it was found that the absolute number of positive IgG4+cells per high power field exceeded 10,and the ratio of IgG4/IgG was over 40%.Finally,the patient was diagnosed with IgG4-TIN complicated with RPF and given glucocorticoids as long-term maintenance therapy,helping him keep out of dialysis.After a follow-up of 19 mo,the patient had recovered well.Previous literature on IgG4-RKD and RPF was retrieved from PubMed to characterize the clinical and pathological features and to identify the diagnosis and treatment of IgG4-RKD.CONCLUSION Our case report demonstrates the clinical characteristics of IgG4-RKD complicated with RPF.Serum IgG4 is a favorable indicator for screening.Performing renal biopsy actively plays a vital role in diagnosis and treatment,even if the patient has a long course and manifests with renal insufficiency.It is remarkable to treat IgG4-RKD with glucocorticoids.Hence,early diagnosis and targeted therapy are essential for reversing renal function and improving extrarenal manifestations in patients with IgG4-RKD.

IgG4-related sclerosing disease

Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prosrate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AlP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4- related sclerosing diseases. This disease includes AlP, sclerosing cholangitis, cholecystitis, sialadenitis, retro-peritoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AlP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunos-taining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.

Autoimmune hepatitis and IgG4-related disease

IgG4-related disease(IgG4-RD) is a chronic-fibroinflammatory disorder affecting a wide range of organs. Elevation of serum IgG4 concentrations and abundant infiltration of IgG4-expressing plasma cells are key diagnostic features of this autoimmune disease. Although common organ involvement of IgG4-RD includes the salivary glands, pancreas, and bile duct, hepatic involvement is less well established. Recently, five studies identified a subtype of autoimmune hepatitis(AIH), called IgG4-associated AIH(IgG4-AIH). IgG4-AIH is diagnosed based on significant accumulation of IgG4-expressing plasmacytes in the liver in patients who met the diagnostic criteria for classical AIH. Although four of the five reports regarded IgG4-AIH based on hepatic accumulation of IgG4-positive cells alone, one report diagnosed IgG4-AIH based on both hepatic accumulation of IgG4-positive cells and elevated serum concentrations of IgG4. IgG4-AIH diagnosed based on the latter criteria may be a hepatic manifestation of IgG4-RD whereas IgG4-AIH diagnosed based on the former criteria may be a subtype of AIH. In this review article, we summarize and discuss clinicopathological features of IgG4-AIH.

Autoimmune pancreatitis in the context of IgG4-related disease:Review of imaging findings

Current understanding of autoimmune pancreatitis (AIP) recognizes a histopathological subtype of the disease to fall within the spectrum of IgG4-related disease. Along with clinical, laboratory, and histopathological data, imaging plays an important role in the diagnosis and management of AIP, and more broadly, within the spectrum of IgG4-related disease. In addition to the defined role of imaging in consensus diagnostic protocols, an array of imaging modalities can provide complementary data to address specific clinical concerns. These include contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for pancreatic parenchymal lesion localization and characterization, endoscopic retrograde and magnetic resonance cholangiopancreatography (ERCP and MRCP) to assess for duct involvement, and more recently, positron emission tomography (PET) imaging to assess for extra-pancreatic sites of involvement. While the imaging appearance of AIP varies widely, certain imaging features are more likely to represent AIP than alternate diagnoses, such as pancreatic cancer. While nonspecific, imaging findings which favor a diagnosis of AIP rather than pancreatic cancer include: delayed enhancement of affected pancreas, mild dilatation of the main pancreatic duct over a long segment, the “capsule” and “penetrating duct” signs, and responsiveness to corticosteroid therapy. Systemic, extra-pancreatic sites of involvement are also often seen in AIP and IgG4-related disease, and typically respond to corticosteroid therapy. Imaging by CT, MR, and PET also play a role in the diagnosis and monitoring after treatment of involved sites.

IgG4-related autoimmune pancreatitis overlapping with Mikulicz's disease and lymphadenitis:A case report

Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-IgG4-related disease.We report a case of IgG4-related AIP overlapping with Mikulicz’s disease and lymphadenitis,which is rare and seldom reported in literature.A 63-year male from Northeast China was admitted for abdominal distension lasting for one year.He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo.He had a 2-year history of bilateral submandibular lymphadenopathy without pain.He underwent surgical excision of the right submandibular lymph node one year prior to admission.He denied any history of alcohol,tobacco,or illicit drug use.Serological examination revealed high fasting blood sugar level(8.8 mmol/L)and high level of IgG4(15.2 g/L).Anti-SSA or anti-SSB were negative.Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation.Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens.The patient received a dose of 30 mg/d of prednisone for three weeks.At this three-week follow-up,the patient reported no discomfort and his swollen salivary glands,neck lymph node and pancreas had returned to normal size.The patient received a maintenance dose of 10mg/d of prednisone for 6 mo,after which his illness had not recurred.

CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series

AIM:To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease(IgG4-MALT lymphoma),a rare but clinically important complication of ocular adnexal IgG4-related disease.METHODS:We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three ter tiary and one secondary referral centers,between February 2003 and December 2016.Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified.CT and MR images were analyzed by consensus of two experienced head and neck radiologists.RESULTS:Lacrimal glands were the main site of involvement in all seven patients.The lesions typically showed well-demarcated margins,iso-to hyperattenuation on precontrast CT,T2 hypo-to isointensity,T1 isointensity,and homogenous internal architecture with homogenous enhancement pattern.Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images,respectively.CONCLUSION:Unlike in typical ocular adnexal IgG4-related disease,T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases.Although the findings may be nonspecific,the possibility of accompanying MALT lymphoma may need to be considered,when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients.However,this is a case series of a very rare complication of ocular adnexal IgG4-related disease,and thus caution is warranted to generalize the conclusion.

Roles of plasmablasts in IgG4-related disease and various immune-based diseases

IgG4-related disease(IgG4-RD) is a systemic fibroinflammatory disease with multiple organ disorders.Recently,in IgG4-RD,increased circulating plasmablasts have been found.The subsets of plasmablasts are negative for RP105(CD180).A large population of B cells lacking RP105(RP105-negative B cells) are found inpatients with active with systemic lupus erythematosus and other systemic autoimmune diseases,including dermatomyositis,and Sj?gren's syndrome.In other conditions,such as neuromyelitis optica,Kawasaki's disease,primary biliary cirrhosis and aging,RP105 expression on B cells and monocytes also alters.We review the basic science and clinical significance of RP105-negative B cells including plasmablasts in various immune-based diseases.RP105-negative B cells,especially plasmablasts,play crucial roles in both systemic and organ-specific autoimmune and inflammatory disorders.

Highlighting the importance of early diagnosis in progressive multi-organ involvement of IgG4-related disease: A case report and review of literature

IgG4-related disease(IgG4-RD)is an increasingly recognized pathological entity that tends to involve multiple organs with an elevated level of serum IgG4,which is easily misdiagnosed owing to sharing common clinical features with a variety of other diseases.Here,we report an interesting IgG4-RD case of a woman with progressive multi-organ involvement for over 19 years,started with swollen eyelids,dry eye and mouth,and polydipsia and hydruria.Imaging diagnosis revealed diffuse enlargement of the parotid glands,enlargement of the head of the pancreas,pulmonary infection and interstitial lung.Serological tests showed a remarkable elevation of the serum IgG4,and cytological analysis further revealed a large amount of lymphoplasmacytic infiltration into the focal lobule,and IgG 4-positive cell infiltration in bladder mucosa.Therapeutically,the patient responded well to steroid therapy,and thus,she was diagnosed as IgG 4-RD suspicious.This report highlights the importance of an early diagnosis in this autoimmune disease and suggests that patients with a clinically unclear cause of inflammation,swelling and refractory glands,rhinitis,pancreatitis,hypophysitis,and/or interstitial pneumonia should be considered for IgG 4-RD.The plasma IgG4 level and lymphoplasmacytic infiltration may be useful indexes for screening,and a low dose of steroid maintaining therapy may offer benefits for patients with IgG4-RD.

IgG4水平及IgG4/IgG比值对IgG4相关性疾病的临床价值

目的探讨血清免疫球蛋白(Ig)G4水平及IgG4/IgG比值在IgG4相关性疾病(IgG4-RD)的鉴别诊断及疗效观察中的应用价值。方法2020年8月至2023年2月于南方医科大学附属广东省人民医院就医并确诊的155例自身免疫性疾病患者作为研究对象,其中IgG4-RD患者60例(IgG4-RD组),其他疾病95例(其他疾病组,包括干燥综合征患者31例,血管炎患者19例,系统性红斑狼疮患者19例,强直性脊柱炎患者5例,类风湿性关节炎患者14例,斯蒂尔病患者3例,皮肌炎患者2例,系统性硬化症患者2例)。另选取50例体检健康者作为对照组。采用免疫比浊法检测各组标本血清IgG4、IgG水平,并计算IgG4/IgG比值。绘制受试者工作特征(ROC)曲线评价血清IgG4水平、IgG4/IgG比值鉴别诊断IgG4-RD的最佳cut-off值、灵敏度及特异度。比较IgG4-RD患者治疗前后IgG4水平、IgG4/IgG比值及其他实验室指标的差异。结果IgG4-RD组血清IgG4水平、IgG4/IgG比值均明显高于其他疾病组和健康对照组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,IgG4诊断IgG4-RD的最佳cut-off值为1.93 g/L,灵敏度为96.7%,特异度为86.2%,AUC为0.928;IgG4/IgG比值诊断IgG4-RD的最佳cut-off值为13.9%,灵敏度为90.9%,特异度为84.3%,AUC为0.933。经激素治疗前后,17例IgG4-RD患者血清IgG4水平及IgG4/IgG比值差异有统计学意义(P<0.05),其中有16例患者血清IgG4水平下降率大于IgG4/IgG比值。IgG4-RD组血清指标阳性率较高的3个指标是红细胞沉降率(ESR)、抗核抗体(ANA)、类风湿因子(RF)。其他疾病组中IgG4水平及IgG4/IgG比值较高的为皮肌炎组、强直性脊柱炎组、血管炎组。结论血清IgG4水平、IgG4/IgG比值对IgG4-RD患者有较高的诊断效能。经激素治疗后,IgG4-RD患者血清IgG4比IgG4/IgG比值下降更明显,但在其他自身免疫性疾病及健康人群中血清IgG4及IgG4/IgG比值也存在升高,需要结合其他指标综合判断。

A clinicopathological study on IgG4-related ophthalmic disease

AIM： To investigate clinicopathological features of immunoglobulin G4-related ophthalmic disease（IgG4-ROD）, and analyze the recurrence rates following systemic corticosteroid administration.METHODS： We retrospectively searched clinical features, laboratory and histological findings based on the medical records of 21 patients with IgG4-ROD. All the patients examined in this study underwent surgical resection in the ocular adnexal lesions and underwent histological evaluation. This study further investigated clinical and histopathological features of 15 patients who received systemic corticosteroid after the resection.RESULTS： The mean age of the patients consisting of 7 males（33%） and 14 females（67%） was 61y. Fourteen patients were diagnosed as definitive, and 2 and 5 patients were probable and possible IgG4-ROD, respectively. Eyelid swelling was an initial symptom in 11 patients（52%） who did not show systemic involvements at a diagnosis. Fifteen patients received systemic corticosteroid administration, and all showed remission of inflammation. Among them, 10 patients did not recur, whereas 5 patients（33%） recurred during tapering. There were no significant difference between patients with or without recurrence in clinicopathological features.CONCLUSION： In this study, female patients are more predominant in IgG4-ROD. While inflammation recurs in one-third of patients, this study do not identify factors associated with recurrence after systemic corticosteroid administration.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician.There is a lack of adequate epidemiological data worldwide,and evidence-based treatment recommendations are not yet established.We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis,orbital myositis,orbitopathy,uveitis,scleritis,sialadenitis,autoimmune pancreatitis and prostatitis.CASE SUMMARY A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss,diarrhoea,abdominal pain,salivary gland swelling,sicca symptoms and diplopia.On examination,bilateral palpable masses in the projection of major salivary glands,severe protrusion of the left eyeball and cachexia were noted.The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy.The magnetic resonance imaging(MRI)of the head revealed enlarged extraocular muscles indicating orbital myositis.The biopsy from the salivary gland mass indicated sialadenitis.Abdominal MRI showed signs of autoimmune pancreatitis,and a serological test revealed the elevated serum IgG4 concentration.The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone.There was a significant clinical,serological and radiological improvement after one month of treatment and no signs of relapse within twenty months.However,it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis.CONCLUSION A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions,such as IgG4-RD.

IgG4 Related Disease as a Differential Diagnosis in Multi-Organ Systemic Disease

IgG4 related disease is a relatively recently recognized systemic entity, that has been observed in nearly every organ system, with similar histopathological features across all identified organs. IgG4 is an antibody molecule accounting for less than 5% of the total IgG count in a healthy person. The molecule is implicated in numerous autoimmune diseases;however its role in IgG4 related disease, whether primary or secondary, remains unknown. The gold standard in the diagnosis of this condition is demonstration of organ involvement from biopsy specimens. In this case report, the patient had exhibited symptoms related mainly to the gastrointestinal tract for 12 years prior to his diagnosis of IgG4 related disease. After this patient’s diagnosis of IgG4 related disease, he was commenced on Rituximab, a monoclonal antibody, which was successful in subsiding his symptoms and he has remained symptom free for the past two years of follow up since commencing treatment and hadn’t developed any complications of the disease nor any complications related to treatment. IgG4 related disease is a systemic autoimmune disease that involves multiple organs 60% - 90% of the time, therefore clinicians should be aware that IgG4 related disease can mimic some autoimmune rheumatic diseases and place it as a differential diagnosis when multi-organ disease with systemic features is involved.

A Case of Acute Renal Failure Associated with IgG4-Related Disease Presenting Both Tubulointerstitial Nephritis and Retroperitoneal Fibrosis

We report a case of IgG4-related disease presenting both tubulointerstitial nephritis and retroperitoneal fibrosis causing acute renal failure in a 63-year-old male. He was admitted to our hospital because of acute renal failure requiring emergent hemodialysis. Computed tomography showed a soft-tissue density mass with an irregular border in the retroperitoneum. The mass involved bilateral ureters and had caused acute renal failure by bilateral hydronephrosis. Because of a history of uveitis and high IgG4 levels, we considered a diagnosis of retroperitoneal fibrosis, IgG4-related disease. Kidney biopsy revealed IgG4-related kidney disease with interstitial nephritis. After relief of urinary obstruction by inserting ureteral catheters into the bilateral ureters, renal function recovered.

IgG4 Coronary Arteritis Presenting as a Cardiac Pseudo-Tumour

We report on an unusual case presenting with a cardiac pseudo-tumour on echocardiogram, which corresponded to a large soft tissue mural thickening around the mid-right coronary artery. There were similar but not as thick mural lesions around other parts of the coronary arteries. The so-called “pigs-in-a-blanket” sign on computed tomography (CT) scan was pathognomonic of IgG4 coronary arteritis. The IgG4 level was grossly elevated at more than 10 times the upper limit of normal. Positron emission tomography (PET)-CT scans with 18F-fluoro-deoxy-glucose (FDG) and 68Ga-Fibroblast Activation Protein Inhibitor (FAPI) were performed to assess the extent of organ involvement of the IgG4-related disease. The patient was treated with 8 injections of rituximab with good serological response. However, the coronary arteritis findings on CT scan remained unchanged.

IgG4-Related Disease Presenting as a Soft Tissue Tumor Affecting Skeletal Muscle: A Case Report

Background: IgG4-related disease is a systemic lymphoproliferative syndrome that shows IgG4-producing plasma cell expansion in affected organs with fibrotic or sclerotic changes. The lacrimal glands, salivary glands and pancreas are typically affected. We report a case of IgG4-related disease presenting a soft tissue tumor affecting skeletal muscle. Case Report: A 32-year-old man presented a soft tissue mass in his left arm. Magnetic resonance imaging revealed a spindle like, peripheral mass, in the lateral head of the triceps of his left arm. Tru-Cut Biopsy provided the diagnosis of IgG4-related disease affecting skeletal muscle. Glucocorticoid treatment was effective. Conclusion: To our knowledge, this is the first reported case of IgG4-related disease affecting skeletal muscle and presenting a soft tissue mass.

血清IgG4和IgGR在IgG4桥本甲状腺炎中的应用

目的 探讨血清甲状腺自身抗体、IgG4、IgG水平和IgG比值(IgGR)等免疫指标在IgG4桥本甲状腺炎(IgG4 HT)中的临床应用价值。方法 选取2019年1月至2022年4月来该院就诊的101例IgG4 HT患者为研究对象,结合其临床表现和促甲状腺刺激激素(TSH)结果将其分为HT甲状腺功能亢进组(简称HT甲亢组)33例、HT甲状腺功能正常组(简称HT正常甲功组)36例、HT甲状腺功能减退组(简称HT甲减组)32例。选择41例同时期表观健康者作为正常对照组。分别采集各组的血清标本并检测IgG4、IgG、IgGR、TSH、抗甲状腺球蛋白抗体(Tg-Ab)和抗甲状腺过氧化物酶抗体(TPO-Ab)项目。通过受试者工作特征(ROC)曲线分析IgG4、IgG和IgGR的检验效能。结果 HT正常甲功组和HT甲减组血清IgG4和IgGR水平与正常对照组比较,差异有统计学意义(P<0.05);HT正常甲功组和HT甲减组血清IgG4和IgGR水平与HT甲亢组比较,差异有统计学意义(P<0.05)。HT甲亢组、HT正常甲功组和HT甲减组TPO-Ab和Tg-Ab阳性率与正常对照组比较,差异有统计学意义(P<0.05)。ROC曲线分析显示,IgG4+IgGR联合检测的曲线下面积为0.74(95%CI:0.66~0.82),当以0.96为截断值,灵敏度为0.56,特异度为0.90。结论 血清IgG4及IgGR作为血清学标志物在IgG4 HT诊断和疾病进展研究方面具有潜在的应用价值。

Comparison of clinical features and outcomes of proliferative,fibrotic,and mixed subtypes of IgG4-related disease:A retrospective cohort study

Background:Immunoglobulin G4-related disease(IgG4-RD)is a recently recognized immune-mediated disorder that can affect almost any organ in the human body.IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’clinicopathological characteristics.This study aimed to compare the clinical manifestations,laboratory findings,and treatment outcomes of IgG4-RD among different subtypes.Methods:We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021.The patients were divided into three groups according to their clinicopathological characteristics:proliferative,fibrotic,and mixed subtypes.We compared demographic features,clinical manifestations,organ involvement,laboratory tests,and treatment agents across three subtypes.We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants.Moreover,risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results:We classified the 622 patients into three groups consisting of 470 proliferative patients,55 fibrotic patients,and 97 mixed patients,respectively.We found that gender distribution,age,disease duration,and frequency of allergy history were significantly different among subgroups.In terms of organ involvement,submandibular and lacrimal glands were frequently involved in the proliferative subtype,while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype.The comparison of laboratory tests revealed that eosinophils(P=0.010),total IgE(P=0.006),high-sensitivity C-reactive protein(P<0.001),erythrocyte sedimentation rate(P<0.001),complement C4(P<0.001),IgG(P=0.001),IgG1(P<0.001),IgG4(P<0.001),and IgA(P<0.001),at baseline were significantly different among three subtypes.Compared with proliferative and mixed subtypes,the fibrotic subtype showed the lowest rate of relapse(log-rank P=0.014).Conclusions:Our study revealed the differences in demographic characteristics,clinical manifestations,organ involvement,laboratory tests,treatment agents,and outcomes across proliferative,fibrotic,and mixed subtypes in the retrospective cohort study.Given significant differences in relapse-free survival among the three subtypes,treatment regimens,and follow-up frequency should be considered separately according to different subtypes.Trial Registration:ClinicalTrials.gov,NCT01670695.