Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level:A single-center,retrospective cohort study

BACKGROUND Autoimmune pancreatitis(AIP)has been linked with elevated immunoglobulin(Ig)G4 levels.The characteristics and outcomes of AIP based on serum markers have not been fully evaluated.AIM To compare clinical features,treatment efficacy,and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse.METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021.According to the serum IgG4 level,all patients were divided into two groups,the abnormal group(n=148)with a high level of IgG4[>2×upper limit of normal(ULN)]and the normal group(n=65).The t-test or Mann-Whitney U test was used to compare continuous variables.Categorical parameters were compared by theχ^(2) test or Fisher’s exact test.Kaplan-Meier curves Zhou GZ et al.Clinical characteristics and outcome of AIP WJG https://www.wjgnet.com 5126 September 21,2023 Volume 29 Issue 35 and log-rank tests were established to assess the cumulative relapse rates.Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse.RESULTS Compared with the normal group,the abnormal group had a higher average male age(60.3±10.4 vs 56.5±12.9 years,P=0.047);higher level of serum total protein(72.5±7.9 g/L vs 67.2±7.5 g/L,P<0.001),IgG4(1420.5±1110.9 mg/dL vs 252.7±106.6 mg/dL,P<0.001),and IgE(635.6±958.1 IU/mL vs 231.7±352.5 IU/mL,P=0.002);and a lower level of serum complement C3(100.6±36.2 mg/dL vs 119.0±45.7 mg/dL,P=0.050).In addition,a lower number of cases with abnormal pancreatic duct and pancreatic atrophy(23.6%vs 37.9%,P=0.045;1.6%vs 8.6%,P=0.020,respectively)and a higher rate of relapse(17.6%vs 6.2%,P=0.030)were seen in the abnormal group.Multivariate analyses revealed that serum IgG4[(>2×ULN),hazard ratio(HR):3.583;95%confidence interval(CI):1.218–10.545;P=0.020]and IgA(>1×ULN;HR:5.908;95%CI:1.199–29.120;P=0.029)and age>55 years(HR:2.383;95%CI:1.056–5.378;P=0.036)were independent risk factors of relapse.CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate.Several factors,such as IgG4 and IgA,are associated with relapse.

Clinical characteristics and outcomes of autoimmune pancreatitis based on serum immunoglobulin G4 levels:A single-center,retrospective cohort study

Autoimmune pancreatitis(AIP)is a complex,poorly understood disease gaining increasing attention."Clinical Characteristics and Outcome of AIP Based on Serum IgG4 levels,"investigated AIP with a focus on serum immunoglobulin(Ig)G4 levels.The 213 patients with AIP were classified according to serum IgG4 levels:Abnormal(elevated)and normal.Patients with higher IgG4 levels exhibited a more active immune system and increased relapse rates.Beyond IgG4,the IgA levels and age independently contributed to relapse risk,guiding risk assessment and tailored treatments for better outcomes.However,limitations persist,such as no IgA correlation with IgG4 levels,absent data on autoantibodypositive AIP cases critical for Asian diagnostic criteria,and unexplored relapse rates in high serum IgG AIP by subtype.Genetic factors and family histories were not addressed.As the understanding and referral of seronegative AIPs increase,there's a growing need for commercially available,highly sensitive,and specific autoantibodies to aid in diagnosing individuals with low or absent serum IgG4 levels.

A Nested Case-Control Study to Explore the Association between Immunoglobulin G N-glycans and Ischemic Stroke

Objective This study prospectively investigates the association between immunoglobulin G(IgG)N-glycan traits and ischemic stroke(IS) risk.Methods A nested case-control study was conducted in the China suboptimal health cohort study,which recruited 4,313 individuals in 2013–2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. Ig G N-glycans in baseline plasma samples were analyzed.Results A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks(GPs) were separated from Ig G N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference,obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men(FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio(OR) = 0.92, 95% confidence interval(CI): 0.87–0.97;G1n: OR = 0.74, 95% CI: 0.63–0.87;G0n: OR =1.12, 95% CI: 1.03–1.22). However, these associations were not found among women.Conclusion This study validated that altered Ig G N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.

Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report

BACKGROUND Immunoglobulin G4-related prostate disease(IgG4-RPD)characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings.Here we report a case of a patient who was successfully treated for IgG4-RPD,which manifested as frequent micturition,dysuric,and systemic lymphadenopathy.CASE SUMMARY The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years.A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L.Computed tomography(CT)revealed bilateral lacrimal gland,right parotid gland and prostatic enlargement.Based on these findings,IgG4-RD was suspected,and further pathological examination and follow-up results showed expected results.Finally,the patient was diagnosed with IgG4-RPD based on clinical symptoms,pathological examination,therapeutic effects,and follow-up results.He received 50 mg oral prednisolone(the dose was gradually reduced and a low dose was used for long-term maintenance)in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo.One year after the treatment was initiated,he was free of urinary or other complaints and his serum IgG4 level normalized.CONCLUSION In IgG4-RPD with severe urinary tract symptoms,radiological findings should be carefully examined.IgG4-RPD prognosis is good because the disease responds well to glucocorticoids.Furthermore,it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.

Studies on Human Immunoglobulin G from GBS Patient (Ⅲ)-The Determination of Molecular Weight of Human Immunoglobulin G by Capillary SDS Gel Electrophoresis

Guillain-Barre syndrome (GBS) is considered to be an autoimmune disorder of peripheralnervous system. In this paper. capillary SDS gel electrophoresis was performed on neutral coatedfused-silica capillary to determine the molecular weight of purified IgG samples from GBS patient.

Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome:A prospective multi-centre cohort study

BACKGROUND Autoimmune markers including plasma cells(PC),anti-smooth-muscle antibody(ASMA),anti-nuclear antibody(ANA),and raised immunoglobulin G(IgG)are commonly observed in non-alcoholic steatohepatitis(NASH),however their clinical significance is unknown.AIM To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes.METHODS Consecutive patients with biopsy proven NASH from Christchurch Hospital,New Zealand and Singapore General Hospital(SGH)were included between 2005 to 2016 in a prospective multi-centre cohort study.Patients with other causes of chronic liver disease were excluded.IgG>14 g/L or globulin fraction>50%,ANA≥1:40,SMA≥1:40 were considered positive.Multivariate analysis was performed to assess which markers were independently associated with mortality and hepatic decompensation.RESULTS Total 261 patients were included of which 201 were from SGH.The median age was 53 and 51.9%were male.Advanced fibrosis was present in 31.4%at diagnosis.PC,ASMA,ANA and raised IgG were observed in 13.1%,4.9%,27.8%and 30.1%of patients respectively.After multivariate analysis,elevated IgG[Hazard Ratio(HR)6.79,95%CI:2.93-17.15]and fibrosis stage(HR 1.37,95%CI:1.03-1.87)were found to be independently associated with increased risk of liver decompensation.Age(HR 1.06,95%CI:1.02-1.10)and elevated IgG(HR 3.79,95%CI:1.90-7.68)were independent factors associated with higher mortality risk.CONCLUSION Elevated IgG,rather than ANA,ASMA or plasma cells,is independently associated with increased risk of hepatic decompensation and mortality in NASH.It could hence be important for prognostication.

Influence of birth order, birth weight, colostrum and serum immunoglobulin G on neonatal piglet survival

Background： Intake of colostrum after birth is essential to stimulate intestinal growth and function, and to provide systemic immunological protection via absorption of Immunoglobulin G （IgG）. The birth order and weight of 745 piglets （from 75 litters） were recorded during a one-week period of farrowing. Only pigs weighing greater than 0.68 kg birth weight were chosen for the trial. Sow colostrum was collected during parturition, and piglets were bled between 48 and 72 hours post-birth. Piglet serum IgG and colostral IgG concentrations were determined by radial immunodiffusion. Results： Sow parity had a significant （P 〈 0.001） effect on sow colostral IgG concentration, being 5% higher in multiparous females. Sow colostral IgG concentration explained 6% and piglet birth order accounted for another 4% of the variation observed in piglet serum IgG concentration （P 〈 0.05）; however, birth weight had no detectable effect. Piglet serum IgG concentration had both a linear （P 〈 0.05） and quadratic effect （P 〈 0.05） on % survival. Piglets with 1,000 mg/dl serum IgG or less （n=24） had a 67% survival; whereas, piglets with IgG concentrations between 2250 to 2500 mg/dl （n=247） had a 91% survival. Birth order had no detectable effect on survival, but birth weight had a positive linear effect （P 〈 0.05）. Piglets weighing 0.9 kg （n = 107） at birth had a 68% survival rate, and those weighing 1.6 kg （n = 158） had an 89% survival. Conclusion： We found that the combination of sow colostrum IgG concentration and birth order can account for 10% of the variation of piglet serum IgG concentration and that piglets with less than 1,000 mg/dl IgG serum concentration and weight of 0.9 kg at birth had low survival rate when compared to their larger siblings. The effective management of colostrum uptake in neonatal piglets in the first 24 hrs post-birth may potentially improve survival from birth to weaning.

An aortoduodenal fistula as a complication of immunoglobulin G4-related disease

Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm,which can be part of immunoglobulin G4(IgG4)-related sclerosing disease.We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level.A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula.The patient received antibiotics and other supportive therapy,and the postoperative course was uneventful,however,elevated levels of serum IgG,IgG4 and C-reactive protein were noted,which normalized after the introduction of steroid therapy.Control computed tomography angiography showed no endoleaks.The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm.Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair.

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab:A case report

BACKGROUND Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events,the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4(IgG4)related disease when the pancreaticobiliary system is affected.Nivolumab,an IgG4 monoclonal antibody,has been associated with cholangitis and pancreatitis,however its association with IgG4 related disease has not been reported to date.CASE SUMMARY We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma.Patients IgG4 levels was normal on presentation.She responded to steroids but due to concerns for malignant biliary stricture,she opted for surgery,the pathology of which suggested IgG4 related disease.CONCLUSION We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.

Novel mechanism of hepatobiliary system damage and immunoglobulin G4 elevation caused by Clonorchis sinensis infection

Clonorchis sinensis infection is still a major public health problem.It is estimated that more than 15 million people worldwide are infected,especially in Northeast China,Taiwan,South Korea,and North Vietnam.The detection of Clonorchis sinensis eggs in feces and bile is still the only gold standard for the diagnosis of Clonorchis sinensis infection,and new detection methods are needed to improve the detection rate.After Clonorchis sinensis invades the human body,it mainly parasitizes the hepatobiliary tract.Therefore,it is closely related to hepatobiliary diseases such as cholangitis,bile duct stones,liver fibrosis,and cholangiocarcinoma.The increase in immunoglobulin G4(IgG4)caused by Clonorchis sinensis infection is rare and there are few reports about the relevant mechanism.It may be related to the inflammatory factors interleukin(IL)-4,IL-10,and IL-13 produced by human phagocytes,T cells,B cells,and other immune cells in the process of resisting the invasion of Clonorchis sinensis.However,this finding still needs further clarification and confirmation.This article reviews the epidemiology,clinical manifestations,serology,imaging,pathogenic mechanism,and control measures of Clonorchis sinensis infection to help establish the diagnostic process for Clonorchis sinensis.We report novel mechanisms of IgG4 elevation due to Clonorchis sinensis infection to provide more experience and a theoretical basis for clinical diagnosis and treatment of this infection.

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis and nivolumab

This letter to editor discussing on the publication on immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab.Concerns on confounding factors are raised and discussed.

Immunoglobulin G4-related disease involving multiple systems:A case report

BACKGROUND Ig G4-related disease(Ig G4-RD),an immune-mediated chronic progressive fibroinflammatory disease,can affect the functions of several organs.Some common characteristics can be observed in different Ig G4-RDs,such as higher prevalence in middle-aged and elderly male patients,raised serum Ig G4 levels,abundant infiltration of Ig G4-positive cells and fibrosis,diffuse or localized swelling of the affected organs,and good response to glucocorticoids treatment.CASE SUMMARY A 72-year-old man complained of left upper abdominal pain 3 mo ago,and he was diagnosed with acute onset of chronic cholecystitis and acute pancreatitis in the local hospital.Pain improved after relevant treatment.Several days ago,his abdominal pain worsened,and he was admitted to our hospital for further treatment.Doppler ultrasound showed that the pancreas presented with sausagelike swelling and the parenchymal echo was diffusely reduced.Gallbladder volume was increased,while the wall was rough and thickened with bilateral signs.Furthermore,the left submandibular gland was enlarged,accompanied with significantly increased blood flow signals.Finally,we found that the adventitia of the abdominal aorta and right iliac artery was thickened locally.Serum Ig G4 was elevated to 12600 mg/L.Therefore,the patient was diagnosed with Ig G4-RD.After treatment with methylprednisolone,he had an uneventful course and was discharged in good condition.CONCLUSION Ig G4-RD can involve almost any organs.Ultrasound has a significant role in timely and accurately diagnosis.

Efficient Expression and Purification of Fc-fragment-binding Domain and Its Application to Immunoglobulin G Purification

The number of therapeutic monoclonal antibodies used in clinical trials has recently increased dramatically, leading to the development of optimized downstream purification processes[1]. Staphylococcal protein A （SPA）, a cell-wall protein of Staphylococcus aureus, has been developed as a universal ligand for immunoglobulin G （IgG） purification because it binds specifically to the Fc portion of the IgG molecule of many mammals[2]. However, certain characteristics of SPA severely restrict the advancement of the antibody industry.

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis:A case report

BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC,however,the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition.Therefore,the information of our recent case and reported cases have been summarized.CASE SUMMARY We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4,narrowing of the bile duct,its wall thickness,no complication of autoimmune pancreatitis,and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes.The cholangiogram revealed type 2b according to the classification.Corticosteroid treatment showed a favorable effect,with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.CONCLUSION As isolated type 2b,IgG4-SC is rare,the images,histological findings,and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report

BACKGROUND Proliferative glomerulonephritis with monoclonal immunoglobulin G(IgG)deposits(PGNMID)is a newly recognized rare disease.The renal pathology is characterized by prominent manifestations of membranous hyperplasia,which are easy to misdiagnose.The clinical symptoms are severe.Massive proteinuria and hypoproteinemia are conspicuous,and most patients are accompanied by renal insufficiency and microscopic hematuria.CASE SUMMARY A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior,and renal biopsy in the hospital suggested moderate-tosevere mesangial proliferating glomerulonephritis(MsPGN).She had taken a glucocorticoid,cyclophosphamide,mycophenolate mofetil,and other treatments and achieved brief partial remission.Recently,the patient visited our hospital due to massive proteinuria.Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli.A bone marrow examination was performed to exclude hematologic malignancy,and a diagnosis of PGNMID was established.The patient showed remission after four cycles of a bortezomib+cyclophosphamide+dexamethasone scheme.CONCLUSION PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis.Although it often occurs in middle-aged and elderly individuals,it cannot be readily excluded in young people,even when serum immunofixation electrophoresis is negative.IgG subtype and light chain staining are necessary when this disease is highly suspected.An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Immunoglobulin G4-related kidney disease involving the renal pelvis and perirenal fat:A case report

BACKGROUND Immunoglobulin(Ig)G4-related disease(Ig G4-RD)is an autoimmune disease associated with chronic and progressive inflammation and fibrosis.It is difficult to differentiate Ig G4-RD involving the kidney from infectious diseases and malignancy on imaging.CASE SUMMARY We report the case of a 51-year-old Chinese man whose abdominal computed tomography scan showed diffuse bilateral enlargement of the kidneys and perirenal fat,thickening of the renal pelvic walls,and hydronephrosis of the right kidney.Relevant laboratory test results showed a serum creatinine level of 464μmol/L.The patient was diagnosed with acute renal failure and was started on intermittent hemodialysis.Further tests revealed high serum Ig G4 levels(20.8 g/L)and an enlarged right submaxillary lymph node.Biopsy and histopathological examination of the enlarged node led to the diagnosis of Ig G4-RD.After corticosteroid therapy,his serum creatinine level quickly decreased to near normal levels.CONCLUSION Ig G4-RD affecting the renal pelvis or perirenal fat is rare,with atypical imaging features.Multidisciplinary consultation is critical for accurate diagnosis and treatment of this disease.Suspected cases should undergo biopsy to avoid misdiagnosis.