Positive IgG4 Research Articles

#1305 Analysis of clinicopathological characteristics of membranous nephropathy with concomitant malignancy and literature review

Abstract Background and Aims In recent years, the incidence of membranous nephropathy (MN) with malignancy has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Method Patients diagnosed with renal biopsy-proven MN and comorbid malignancy detected within 5 years before and after MN diagnosis were included. The control group were diagnosed with renal biopsy-proven IMN with no malignancy and no other clear secondary cause for MN. We present a comprehensive analysis of MN with concomitant malignancy in our cohort and literature review. Results A total of 19 MN patients with concomitant malignancy were evaluated at our center; among them, 13 (68.4%) were male, and the median age was 57.0 (45.0, 69.0) years. Malignancy occurred after the onset of renal disease in 61.1% of patients, with digestive system malignancy (36.8%) ranking as the predominant type. 8 (8/11) patients achieved either PR or CR during the follow-up period. Most patients had pathology typical of IMN. IF showed strong positivity for IgG (100%), whereas only 13 (68.4%) patients were positive for C3. IEM showed electron-dense deposits predominantly located in subepithelial. Specific MN antigen staining of renal tissues from 19 patients showed that the highest percentage was 68.4% (13/19) for PLA2R-only positivity followed by 15.8% (3/19) for THSD7A-only positivity. Specific MN antigen staining of malignant tissue was performed in 5 patients whose tumor samples were available. Only 2 patients expressed the same antigen on kidney and tumor. Screening 17 articles encompassing a total of 21 patients in whom MN-specific antigen staining was performed on both renal and tumor tissues simultaneously. Among these patients, 71.4% (15/21) were male, with a median age of 61.0 years (56.3, 72.8). In this cohort, malignancy was diagnosed before or simultaneously with MN in 15 patients (75.0%), with digestive system malignancy constituting the most prevalent comorbid malignancy, at 33.3%. Notably, THSD7A accounted for the highest proportion of MN antigens, at 66.7% (14/21); among these patients, 78.6% (11/14) also exhibited positive tumor THSD7A staining. Of the 21 patients, 72.2% (13/18) achieved CR or PR. No significant difference between the baseline characteristics was observed between the 19 patients from our center and 21 patients documented in the literature. Therefore, the clinicopathological data of these 40 patients were pooled and compared with 101 IMN patients without malignancy at our center. Compared to patients without malignancy, MN patients with malignancy were older at the time of renal biopsy (P = 0.017), had a lower eGFR (P = 0.035) and demonstrated a lower rate of CR or PR after treatment (P < 0.001). The rate of PLA2R positivity in the glomeruli of MN patients with concomitant malignancy was significantly lower (40.0% vs. 92.1%, P < 0.001), while the rate of THSD7A positivity was significantly higher (42.5% vs. 2.0%, P < 0.001). Renal tissue IgG subclass staining showed that the rate of IgG4 positivity was significantly decreased compared with that in IMN patients (59.3% vs. 90.1%, P < 0.001), and the rate of IgG2 positivity was significantly increased (36.0% vs. 16.5%, P = 0.033). Conclusion To conclude, malignancy screening should be more actively performed for MN patients presenting with the above characteristics.

Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma

BackgroundImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma.Case presentationA 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor.ConclusionIt is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Association between Food-Specific Immunoglobulin G4 Antibodies in Adults with Self-Reported Signs and Symptoms Attributed to Adverse Reactions to Foodstuffs.

Signs and symptoms attributed to adverse reactions to foodstuffs (ARFS) need tools for research and evaluation in clinical practice. The objectives of this study were (a) to evaluate the most frequent self-reported signs and symptoms attributed to ARFS in Spanish adults, (b) to determine the prevalence of food-specific IgG4 antibody reactions (AbRs), and (c) to investigate the association between self-reported ARFS symptomatology and food-specific IgG4 AbRs. Food-specific IgG4 AbRs against 57 common food and beverages (AESKUCARE-T2FA® in vitro point-of-care test kit, Aesku.Diagnostics GmbH, Germany) were determined in capillary blood samples of 205 volunteers living in the Region of Madrid (Spain). The most frequent self-reported signs and symptoms were related to skin (43%), digestive (41%), and nervous system (NS, 33%) problems. The prevalence of food-specific IgG4 AbRs was cow's milk (73%), sheep's milk (70%), casein (66%), and goat's milk (56.10%). Positive IgG4 AbRs against tomato had a profile consisting of 3/4 of skin problems, more than half of digestive, and 2/5 of NS self-reported signs and symptoms. In conclusion, at least 1/3 of the studied sample reported skin, digestive, and NS signs and symptoms. The most frequent food-specific IgG4 AbRs were related to dairy. Skin problems were more frequent in positive tomato IgG4 AbRs.

IgG4 Positivity in Chronic Tonsillitis: A New Component of IgG4-Related Disease?

Immunoglobulin G4-related disease (IgG4-RD) and chronic tonsillitis are both chronic fibroinflammatory diseases in which tissue atrophy is sometimes observed. In this study, the authors aimed to investigate the pathologic IgG4 positivity in tonsillectomy specimens and hypothesized to name it as a new clinical component of IgG4-RD if there is significant IgG4 positivity in chronic tonsillitis. A total of 73 patients who underwent tonsillectomy for chronic tonsillitis were included in this study. Of these, 31 patients had atrophic form chronic tonsillitis. Pathologic examinations and specific IgG4 immunohistochemical staining were performed by the same experienced pathologist in terms of IgG4-RD. Sixty-three percent (n=46) of the cases were male, 37% (n=27) were female, their ages ranged from 3 to 51, and the mean age was 19.11±14.82. It was determined that 23.3% (n=17) of the cases participating in the study were IgG4-positive. When the pathologic grades of the cases were examined; it was observed that 13.7% (n=10) were Grade I, 65.8% (n=48) were Grade II, and 20.5% (n=15) were Grade III. A statistically significant difference was found between the pathology degrees of the cases according to the IgG4 groups ( P =0.001; P <0.01). The authors concluded that as the histopathologic grades of chronic lymphoplasmacytic inflammation in tonsils specimen increase, IgG4 positivity rates also increase. Therefore, this clinical entity may be a new IgG4-related disease state in cases with chronic tonsillitis. Level II.

IgG4-Related Disease, a Systemic or Local Disease: This is the Problem

Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that forms tumefactive lesions in various organs, presenting with diverse clinical manifestations. Diagnosis of IgG4-RD could be challenging and relies on characteristic histopathological findings and elevated IgG4+ plasma cell counts. Case Presentation: The patient was a 48-year-old woman with diabetes mellitus initially presented with a painless breast mass. Imaging indicated irregular opacities and lymph nodes in the breast. Biopsy results revealed lymphoplasmacytic infiltration with IgG and IgG4 positivity, overall compatible with IG4-related disease. A mass resection was performed, and intraoperative assessment ruled out malignancy. Then, with a 5-month interval of no symptoms, the patient developed a cheek mass, initially misdiagnosed as low-grade spindle cell sarcoma. Subsequently, she underwent partial maxillectomy and further examination and histology confirmed IgG4-RD, meeting all diagnostic criteria. Conclusion: IgG4-RD is a rare, systemic fibroinflammatory condition with potential to mimic neoplastic processes. While IgG4 serum levels can be elevated, they are not a reliable diagnostic criterion. The two main features of IgG-related disease are an elevated number of IgG4-positive plasma cells within the tissue and a characteristic histopathological appearance including a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. Overall, diagnosis is based on the balance of clinical features, histopathology, and serum markers. This case underscores the diagnostic challenges posed by IgG4-RD, often mistaken for malignancies due to its invasive behavior and emphasizes the importance of considering IgG4-RD in differential diagnoses for tumor-like lesions, particularly when affecting multiple organs, to enable timely treatment decisions and prevent unnecessary interventions.

A292 ACUTE PANCREATITIS AS THE FIRST PRESENTATION OF GRANULOMATOSIS WITH POLYANGIITIS (GPA): A CASE REPORT

Abstract Background Granulomatosis with Polyangiitis (GPA) is a rare necrotizing ANCA-associated vasculitis characterized by inflammation in small-sized arteries. GPA often presents with a triad of a) upper (nasal obstruction, sinusitis, crusting rhinitis) and lower respiratory tract (lung nodules, alveolar hemorrhage) b) systemic vasculitis and c) kidney involvement (necrotizing glomerulonephritis). However, gastrointestinal involvement is exceedingly rare and only occurs in about 5-11% of GPA cases. Specifically, recurrent acute pancreatitis is even more uncommon. Purpose To raise awareness about systemic vasculitides in cases of idiopathic acute pancreatitis Method A 48-year-old female was seen in an outpatient gastroenterology clinic for recurrent idiopathic pancreatitis. She reported a six-month history of intermittent sharp epigastric pain associated with a rise in lipase. The patient noted having episodes of acute sinusitis shortly prior to the onset of her epigastric pain. Her initial labwork revealed normal creatinine and liver enzymes, elevated total bilirubin 24, lipase 316 and mildly high CRP 16.1 and ESR 27 which normalized on repeat blood work. Abdominal US was unremarkable with no gallstones, intra- or extrahepatic duct dilatation. An abdominal MRI revealed segmental enlargement of the distal tail/body of the pancreas consistent with resolving focal pancreatitis. A follow-up MRI 5 weeks later revealed progression of pancreatic swelling and intermittent narrowing of the pancreatic duct. These findings were suspicious for an inflammatory process such as autoimmune pancreatitis. The patient then underwent EUS-guided examination and FNA of her pancreas. Pathology revealed focal chronic pancreatitis with fibrosis and mild lymphocytic infiltrate, but was not suggestive of autoimmune pancreatitis. She was then treated empirically with a 3-month course of prednisone and had significant improvement in her symptoms and interval resolution of pancreatic inflammation on repeat MRI. After discontinuation of her steroids, her symptoms recurred with intermittent epigastric pain, facial pain and sinusitis. She was then seen by rheumatology and an autoimmune panel was ordered. Result(s) Autoimmune work-up revelead positive anti-PR3 (27 RU/ml), negative anti-MPO and normal IgG-4 levels. Ultimately a diagnosis of limited GPA, which spares the kidneys, was made given the patient’s clinical presentation and positive anti-PR3 antibody. Since there was no life-threatening organ involvement, she was elected to start methotrexate therapy and had significant improvement in her symptoms. The plan is to stay on methotrexate for at least 24 months and have regular follow-up to ensure clinical stability. Conclusion(s) Acute pancreatitis is a rare initial presentation of GPA vasculitis. It is important to consider autoimmune disease and systemic vasculitides in cases of idiopathic pancreatitis after ruling out common causes. Early diagnosis and therapy allow for high rates of remission and improved survival rates. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

The Distinctive Nature of Thyroid MALT Lymphomas Including IRTA1 Expression.

Mucosa-associated lymphoid tissue (MALT) lymphomas often express IgM and IRTA1 with only a minority demonstrating plasmacytic differentiation. However, like primary cutaneous marginal zone lymphoproliferative disorders (PCMZLPD), thyroid MALT lymphomas (T-MALT-L) frequently show plasmacytic differentiation and IgG positivity. Whether T-MALT-L share other features with PCMZLPD, including frequent IgG4 positivity and infrequent IRTA1 expression, and how IRTA1 staining compares to that in Hashimoto thyroiditis (HT) are unknown. Therefore, the clinicopathologic features of 18 T-MALT-L were assessed, and their IRTA1 expression compared with that in 5 HT cases. All T-MALT-L cases included a B-lymphoid component. Plasmacytic differentiation was present in 15 cases and was extensive in 12. Fourteen cases were IgG+ including 2 IgG4+ (12 κ+, 2 κ-/λ-). One case was IgAλ+. Plasmacytic cells were uniformly CD19+/CD56- but CD138- in 7/15 cases. IRTA1+ cells were present in 16/16 cases, ranging from scattered cells to >50%. They were often concentrated in "MALT ball"-type lymphoepithelial lesions, perifollicular regions, and sometimes in germinal centers. IRTA1 positivity was also present in all HT cases, although it was never very extensive and often had a perifollicular distribution, occasionally with sparse aggregates and positive cells within rare thyroid follicles. Thus, T-MALT-L share some features with PCMZLPD but are more similar to noncutaneous MALT lymphomas, with prominent lymphoepithelial lesions, ubiquitous although variable IRTA1 positivity, and infrequent IgG4 positivity. Plasmacytic differentiation is also common although CD138 loss is frequent and light chain staining may be absent. IRTA1 staining may help in the differential diagnosis with HT, although there is some overlap in staining patterns.

A Case of ALECT2 Renal Amyloidosis Associated with IgG4 Related Kidney Disease, Membranous Nephropathy and Early Diabetic Kidney Injury

Abstract Introduction/Objective ALECT-2 amyloidosis is a rare type of amyloidosis that mostly involves kidneys with other organs rarely affected. It has a high prevalence among patients of Hispanic descent. Membranous nephropathy is one of the most common causes of proteinuria in adults. IgG4-related disease is a systemic disease, which commonly involves the pancreas, but occasionally affects the kidney and manifests as chronic renal insufficiency. Here we describe a very unusual case of concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury. Methods/Case Report A 49-year-old Hispanic male patient with a history of diabetes and IgG4-related autoimmune pancreatitis and primary sclerosing cholangitis presented with abrupt onset of proteinuria and hypoalbuminemia. A kidney biopsy was performed and showed severe interstitial plasma cell-rich inflammatory infiltrates and interstitial fibrosis which had a storiform pattern. The glomerular basement membranes (GBM) showed focal pinpoint holes but no spikes by silver stain. Immunofluorescence microscopy (IF) showed diffuse and finely granular capillary loop staining for IgG, with Kappa and lambda light chains of equal intensity. IF for Anti-phospholipase A2 receptor (PLA2R) was negative. Immunohistochemical (IHC) stain showed IgG4 positivity in about 60% of IgG-positive plasma cells. Congo red was positive for birefringent deposits predominantly in the interstitium and arteriolar walls with focal deposits in the glomerular mesangium and capillary wall. IHC stain for Amyloid AA and DNAJB9 were negative. Electron microscopy showed scattered subepithelial immune complex-type electron dense deposits consistent with membranous nephropathy, randomly oriented fibrils in interstitium, mesangium and GBM, consistent with amyloidosis, and thickening of GBM (average 559 nm), consistent with early diabetic kidney change. The tissue was sent for mass spectrometry which showed a peptide profile consistent with ALECT-2 (Leukocyte chemotactic factor 2) type amyloidosis. Results (if a Case Study enter NA) NA Conclusion In up to a third of cases reported in the literature, a concomitant renal pathology was present. Diabetic nephropathy was the most common concurrent pathology, to be followed by IgA nephropathy and membranous nephropathy. However, the concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury has never been described before.

Diagnosis of inflammatory bowel disease according to human IgG4 and possibilities of evaluating efficacy of the therapy

Taking into account the progress of understanding diagnosis, course prognosis, evaluation of effectiveness of therapy of inflammatory bowel disease and also differentiation diagnosis between its main forms – ulcerative colitis and Crohn’s disease, the search for efficient non-invasive markers for solving those issues is extremely relevant. The patients were divided into groups depending on nosology and severity of the course of the disease. All the patients had undergone endoscopic study for diagnosis verification and biopsy samples were taken for further detection of tissue IgG4 using the immunohistochemical method. Also, we determined concentration of serum IgG4. Increase in IgG4content in blood serum was determined in 54.0% of the cases of inflammatory bowel disease. Concentration of IgG4 in patients suffering ulcerative colitis was higher (by 2.31 and 2.46 times) compared with its level in the control group and patients with Crohn’s disease, respectively. We found relationships between the concentration of serum IgG4 and the activity of the disease. In patients with ulcerative colitis, increased tissue IgG4 was found more often than in patients with Crohn’s disease (by 2.77 times, Р &lt; 0.05). We determined the relationship between tissue IgG4 and histological activity. Simultaneous increase in serum IgG4 and presence of tissue IgG4 during ulcerative colitis were more frequent than during Crohn’s disease (by 2.66 times). In all examined groups of patients, we determined decrease in serum IgG4 content (by 1.66 times) after treatment. Concentration of serum IgG4 and positive tissue IgG4 in ulcerative colitis patients exceeded such in Crohn’s disease patients, which may be used for differentiation diagnosis between those disease types. We determined dependence of IgG4 concentration on severity and duration of the disease, which could be used as a prognostic marker. Decrease in IgG4 content in blood serum against the background of the therapy shows that this indicator could be used as a marker of treatment efficacy. Perspectives of further studies are as follows: parameters of concentration of serum IgG4 and presence of tissue IgG4 could be used as diagnostic and prognostic biomarkers and be introduced to practice for differentiation diagnosis between ulcerative colitis and Crohn’s disease, and could be used as prognostic marker of severity of the disease and therapy efficacy.

S3361 Liposarcoma Masquerading as IgG4-Related Disease

Introduction: IgG4-related disease (IGRD) is characterized by lymphoplasmacytic tissue infiltration by IgG4-positive plasma cells and small lymphocytes and is known to involve multiple organs, sometimes simultaneously.1 Retroperitoneal involvement is common with IGRD, often presenting as mass-like lesions and fibrosing disease such as retroperitoneal fibrosis2 and sclerosing mesenteritis3. While there is no established association, very few cases have been reported in literature about strong IgG4 positivity and sarcomas.3,4 Investigation usually warrants biopsy, as imaging studies and serologies cannot differentiate between IGRDs and sarcomas. We present a case of an aggressive liposarcoma mimicking IGRD. Case Description/Methods: A 40-year-old female presented with right upper quadrant (RUQ) pain for 3 months. Patient was hemodynamically stable with physical exam demonstrating fullness and tenderness in RUQ. CT abdomen revealed a 12.9x11.8x8.7 cm heterogenous macro-lobulated mass located below the inferior hepatic border in the retroperitoneal space and hepatorenal recess (Figure A). CT guided biopsy of the mass revealed increased IgG4-positive cells identified by immunohistochemical studies, however, FISH MDM2 amplification studies were inconclusive. Patient’s serum IgG4 levels were elevated, and she was started on prednisone therapy. At 2 month follow-up, the patient’s serum IgG4 levels had decreased but upon physical examination, the mass had increased in size and was firmer. Decision was made to repeat CT-guided biopsy, wherein MDM2 amplification studies revealed that the mass was consistent with well-differentiated liposarcoma (Figure B). She underwent liposarcoma resection, lymph node dissection, and right nephrectomy (adherent to the mass). Histopathologic analysis revealed a final diagnosis of stage I well-differentiated liposarcoma. Patient now follows for surveillance of her liposarcoma. Discussion: IGRD and liposarcoma can have common initial presentations and at times overlapping serological markers such as IgG4 levels, which necessitates histopathologic analysis for confirmation of the disease. In addition, raised IgG4 levels are not specific and can be elevated in infections and autoimmune conditions5. Our case emphasizes the importance of considering liposarcomas in retroperitoneal masses with elevated IgG4 levels, as they can mimic IGRD. A repeat biopsy should be considered if the initial diagnosis is doubtful, or patient responds poorly to corticosteroids.Figure 1.: A) Coronal view of the CT scan showing a macrolobulated heterogenous mass measuring 10.6x10.5x14.1cm, B) MDM2 expression of mass using FISH.

Characteristics and renal survival of patients with lupus nephritis with glomerular immunoglobulin G4 deposition: a single-centre retrospective analysis

ObjectiveRenal injury is common in SLE. Immune complex deposition plays an important role in the development of lupus nephritis (LN), while little is known about glomerular IgG4 deposition in patients...

Clinical analysis of 15 cases with myeloperoxidase antineutrophil cytoplasmic antibody associated hypertrophic pachymeningitis

To study the clinical features of myeloperoxidase(MPO) antineutrophil cytoplasmic antibody (ANCA) associated hypertrophic pachymeningitis (HP). Clinical data of 15 cases diagnosed with MPO-ANCA vasculitis complicated with HP were retrospectively analyzed. Nine cases were males and the other 6 were females, with an average age of (58±8) years. All cases presented with chronic headache. Contrast-enhanced magnetic resonance imaging (MRI) scan showed local or diffused thickening of cerebral and/or spinal dura matter while brain parenchyma were normal. Nine cases developed multiple cranial nerve paralysis, with trigeminal nerve and auditory nerve involved most commonly. The main clinical manifestations were facial pain, hearing loss and tinnitus. Two cases were complicated with hypertrophic spinal pachymeningitis (HSP) and 4 cases were complicated with pulmonary diseases. Positive serum perinuclear pattern ANCA (pANCA) and MPO could be found in all cases, positive serum IgG4 was seen in two patients. erythrocyte sedimentation rate(ESR;25-116 mm/1h) and C-reactive protein (CRP;29.02-146.00 mg/L) were both elevated in 14 cases. Nine cases had elevated intracranial pressure[180-235 mmH2O (1 mmH2O=0.009 8 kPa)] and abnormal protein level (457.6-3710.0 mg/L) in cerebrospinal fluid. Six cases were treated with glucocorticoids (prednisone 20-60 mg/d) and 9 cased with glucocorticoids and immunosuppressants (methotrexate 15 mg/week or cyclophosphamide 100 mg/d po). All patients achieved remission. MPO-ANCA associated HP is a special type of central nervous system involvement in ANCA associated vasculitis (AAV). It rarely involves the lung or kidney. Steroids and immunosuppressive agents are effective. In HP with unknown underlying diseases, it is suggested to screen ANCA and IgG4 tests for AAV or IgG4-related disease.

Respiratory syncytial virus specific immunoglobulin G4 antibodies and atopic diseases in children.

It has been proposed that RSV infection stimulates RSV specific IgE and IgG4 production as a hallmark of Th2 immune response, which can contribute to the development of allergic sensitization and atopic diseases. This study intends to examine the occurrence of atopic diseases in children (wheezing bronchitis, food allergy, atopic dermatitis) and their connection with RSV specific IgE and IgG4 during the first two years of life. Prospective follow-up from the moment of birth was performed in 127 children with positive RSV specific IgG antibodies at age 1 and 92 children were followed-up until two years of age. The assessment included a structured interview, clinical examination, total blood eosinophils, serum total IgE and allergen specific IgE antibodies, RSV specific IgG, IgG3, IgG4 and IgE antibodies. Significant correlation was found between positive RSV IgG4 antibodies at year one and atopic dermatitis (Tau_b=0.201, P=0.025), as well as food allergy development (Tau_b=0.205, P=0.023). RSV specific IgG4 antibodies to RSV at year one showed significant prediction of increased total and/or allergen specific IgE (odds ratio 2.73 and 95% confidence interval 1.07 - 7.00, P=0.036). In our regression model, the children who had positive RSV IgG4 antibodies had a 2.73 times higher likelihood of having increased positive total and/or allergen specific IgE during the first two years of life. RSV specific IgG4 antibodies could be a marker of risk for the development of atopic sensitization to inhaled and food allergens, development of food allergy and atopic dermatitis in atopic children.

Resolving primary membranous glomerulopathy (MGN) reveals a dynamically metabolic pathway from sub-epithelium to glomerular basement membranes

ABSTRACT In idiopathic (primary) membranous glomerulopathy (MGN), there is a phenomenon of subepithelial deposits (stages 1 and 2) transitioned to intramembranous deposits, with lucent resolving features (stages 3 and 4). This phenomenon has not been described in other types of immune complex mediated glomerulonephritis with either subendothelial or mesangial deposits. The goal of this study was to evaluate what unique immunostaining pattern could occur in primary MGNs with intramembranous resolving features. PLA2R and IgG4 immunostains were performed in 50 primary MGNs, and 39 secondary MGNs after the clinical history was reviewed. Primary MGNs with resolving features were further evaluated in detail. A total of 84% (42/50) of primary MGN cases had diffuse positive immunostaining for IgG4 in the glomeruli, and most of them were also positive for PLA2R staining. Eight of the remaining primary MGN cases (8/50) with positive PLA2R but negative IgG4 staining in the glomeruli had diffuse resolving features as observed by electron microscopy. All secondary MGNs were stained negatively for both IgG4 and PLA2R except for one case with positive IgG4 staining but negative staining for PLA2R. Our data indicate that IgG4 staining on paraffin tissue is a very reliable screening tool to confirm the presence of primary MGN. Primary MGN with PLA2R+/IgG4- stains were seen in those with intramembranous resolving features. This finding is consistent with the known weak-binding capacity of IgG4 to the glomerular basement membranes. The transitional phenomenon from PLA2R+/IgG4+ subepithelial deposits to PLA2R+/IgG4- intramembranous resolving deposits in primary MGN implies that there may be a continuous metabolic activity from podocyte to glomerular basement membrane.

IgG4 antibodies against Bm14 as an evaluation tool of mass drug administration in a co-endemic area of Brugia timori and Wuchereria bancrofti

To evaluate the success of mass drug administration for lymphatic filariasis, WHO has recommended two rapid tests, Brugia Rapid (BR) to detect the presence of IgG4 antibodies against Brugia sp and Filariasis Test Strip (FTS) to detect antigens of Wuchereria bancrofti. As a country co-endemic for Brugia sp. and W. bancrofti, Indonesia needs a single diagnostic tool that can detect the exposure to both species. This study aimed to evaluate the efficacy of mass drug administration by measuring Bm14-specific IgG4 levels in blood samples of the population living in a co-endemic area of B. timori and W. bancrofti in Southwest Sumba Regency. A total of 132 plasma samples obtained before and one year after DEC-albendazole administration, which have been previously tested with BR and FTS, were examined for IgG4 against Bm14 using enzyme-linked immunosorbent assay. The results showed that before treatment all 32 individuals (100%) with BR+/ FTS+ were also positive for Bm14-specific IgG4, while in BR+ or FTS+ group there were >90% samples detected positive. At one year after treatment, positive results for Bm14-specific IgG4 were still detected in 96.9% samples with BR+/ FTS+, 78.8% samples with BR+/ FTS- and 82.9% samples with BR-/ FTS+. On the other hand, the BR-/ FTS- group also had high rate of Bm14-specific IgG4 positivity either before treatment (62,5%) and at one year after treatment (43.8%). The lowest decrease of Bm14-specific IgG4 positivity at one year after treatment was shown in the double positive group (3.1%), while the highest was in the double negative group (18.7%). The measurement of IgG4 against Bm14 has the potential as a sensitive diagnostic tool to evaluate the success of MDA in the areas co-endemic for B. timori and W. bancrofti.

\u201cStomach mass\u201d as the first manifestation of IgG4-related disease: a case report

BackgroundIgG4-related disease mainly manifests as organomegaly and is accompanied by tissue fibrosis (Mimori, Mod Rheumatol 29(2):213, 2019) which is frequently confused with tumour (Dawei et al., J Gastroenterol Hepatol 29(12):1375–8, 2020). There are few reports with of IgG4-related disease with the first clinical manifestation involving the stomach.Case presentationWe present the case of 46-year-old male patient with a “stomach tumour” as the first manifestation of IgG4-related disease. Gastroscopy showed a mass in the stomach, however, the pathology result was chronic inflammation with IgG4 positivity. CT scans of abdomen showed that the stomach wall was thick, the head of the pancreas was swollen, and retroperitoneal fibrosis was severe.The serum IgG4 level was 75 g/L (normal range 0.03–2.01 g/L).After treatment with methylprednisolone for one month, the symptoms were greatly relieved.ConclusionsTo reduce the suffering of patients and relieve their financial burden, we should consider the possibility of IgG4-related disease when the initial manifestation is a stomach mass.

IgG4-related disease in patients with idiopathic orbital inflammation

BackgroundTo identify the prevalence of positive IgG4 immunostaining in orbital tissue among patients previously diagnosed with nongranulomatous idiopathic orbital inflammation (IOI) and to compare the clinical characteristics of patients with and without IgG4-positive cells.MethodsA retrospective review of all patients with a histopathologic diagnosis of IOI was performed. Immunohistochemical staining was performed to identify IgG-positive cells and IgG4-positive cells. Multivariate analysis was performed using likelihood ratio-test logistic regression on the differences between IgG4-related disease (IgG4-RD) and non-IgG4-RD.ResultsOf the 45 patients included, 21 patients (46.7%) had IgG4-positive cells, with 52.4% being male and a mean age of 55.9 ± 13.4 years. Bilateral ocular adnexal involvement (adjusted odds ratio [aOR] = 9.45; P = 0.016) and infraorbital nerve enlargement (aOR = 12.11; P = 0.008) were frequently found in IgG4-RD patients. Complete remission occurred in 23.8% of IgG4-RD patients and 41.7% of non-IgG4-RD patients. IgG4-RD patients had more frequent recurrent disease than non-IgG4-RD patients.ConclusionsNearly 50% of IgG4-RD patients were previously diagnosed with biopsy-proven IOI. IgG4-RD was more frequent in patients with bilateral disease and infraorbital nerve enlargement, showing the importance of tissue biopsy in these patients. Immunohistochemistry studies of all histopathology slides showing nongranulomatous IOI are highly recommended to evaluate for IgG4-RD.

A CORRELATION OF NEUROCYSTICERCOSIS AND IGG4 ANTIBODIES

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: In endemic regions, 30% of patients presenting with epilepsy, have evidence of neurocysticercosis. In the US, between the years of 2003 and 2012, there were more than 18,000 hospitalizations for neurocysticercosis. A study done in 2002 showed that IgG4 was found in the sera of patients with cerebral cysticercosis 97.8% of the time. Reliance on immunological assays holds importance due to the lower costs in comparison to imaging studies in impoverished areas. This case presentation follows a patient with a ring-enhancing brain lesion, positive cysticercosis antibodies, and positive IgG4 cells on tissue biopsy. CASE PRESENTATION: A 56-year-old male with a past medical history of hypertension, recent head injury and no other risk factors, presented for evaluation of syncope. Before the syncopal episode, the patient was seen by the primary physician for sustained injury to his head with complaints of recurrent fevers, headache, and blurred vision. The patient was prescribed steroids and antibiotics but did not feel any improvement and ended having a syncopal episode with a brief loss of consciousness. Magnetic resonance imaging of the brain with contrast showed a 17mm right mid corona radiata/mid-lateral ventricle peripherally enhancing mass with surrounding white matter edema and centralized restricted diffusion. Patient was admitted to the intensive care unit and treated with antibiotics, steroids, and antiepileptics. Stereotactic brain biopsy showed brain parenchyma with mildly increased cellularity consisting primarily of glial cells suggestive of reactive tissue. All labs and immunological studies were negative except for positive Cysticercosis IgG Antibody. Computed tomography of the abdomen and pelvis was positive for a 3 cm low-density lesion in the right lobe of the liver for which biopsy showed rare CMV inclusions in infected cells on a background of storiform fibrosis and lymphoplasmacytic inflammation with numerous IgG4 positive cells. The patient was started on albendazole and over the course of a few days, symptoms significantly improved. DISCUSSION: Brain biopsy showed only reactive tissue, hence to ensure no other primary lesion is present, further imaging tests were ordered which led to the revelation of the liver lesion and the biopsy was pathognomonic for IGG4 related disease, however, due to a lack of other necessary diagnostic criteria (serum IgG4 above 135 and histopathology showing IGG4 positive cells greater than 40%), the conclusion was not reached. However, due to the ring-enhancing lesion and positive cysticercosis IgG antibody, neurocysticercosis was higher on the differential as IgG4 is the most commonly found antibody in serum or CSF. CONCLUSIONS: Our findings of a correlation between neurocysticercosis and IgG4, strengthen the promise of a better immunodiagnostic tool thereby fighting the issues of accessibility and cost-effectiveness for endemic areas. REFERENCE #1: O'Neal SE, Flecker RH. Hospitalization frequency and charges for neurocysticercosis, United States, 2003-2012. Emerg Infect Dis. 2015 Jun;21(6):969–76. REFERENCE #2: Huang B, Li G, Jia F, Liu F, Ge L, Li W, et al. Determination of specific IgG4 for diagnosis and therapeutic evaluation of cerebral cysticercosis. Chin Med J (Engl). 2002 Apr;115(4):580–3. REFERENCE #3: Legatowicz-Koprowska M. IgG4-related disease: why is it so important? Cent-Eur J Immunol. 2018;43(2):204–8. DISCLOSURES: No relevant relationships by Rahul Dadhwal, source=Web Response no disclosure on file for Lauren Howard; No relevant relationships by Alamgir Khan, source=Web Response No relevant relationships by Katrina Rathjen, source=Web Response No relevant relationships by Salim Surani, source=Web Response

Plasma cell IgG4 positivity in orbital biopsies of non-IgG4-related conditions.

The IgG4-related disease (IgG4-RD) is a systemic condition defined as a fibro-inflammatory disorder, characterized by the occurrence of tumor-like lesions in multiple organs including the eye adnexa. The main diagnostic criterion is based on histopathological findings, especially on the IgG4+/IgG+ plasma cell ratio. In this article, we reviewed the literature of non-IgG4-RD orbital conditions with IgG4 positivity. There were 20 reports of inflammatory non-IgG4-RD orbital lesions and 14 reports of orbital lymphoid proliferations with significant IgG4 positivity. The role of plasma cells IgG4 in the pathogenesis of non-IgG4-RD is not clear. Considering the large spectrum of diseases caused by a variety of different etiopathogenic mechanisms, we think that the common denominator of IgG4+ in these conditions might be related to the peculiar properties of down regulation of immune response of the IgG4 and not to a specific link to IgG4-RD.

Long-Term Outcomes of Tamoxifen Citrate Therapy and Histo- and Immunopathological Properties in Riedel Thyroiditis

Background: Riedel thyroiditis (RT) is a rare form of thyroiditis; thus, data about the disease course and treatment options are limited. Therefore, we aimed to assess the clinical, serological, radiological, and histopathological features, as well as short- and long-term follow-up of RT patients under glucocorticoid (GC) and tamoxifen citrate (TMX). Parameters related to IgG4-related diseases (IgG4-RD) were also investigated. Methods: Eight patients with RT diagnosed between 2000 and 2019 were enrolled. Data were collected in a retrospective and prospective manner. The diagnosis was confirmed with histopathological features in all patients. Results of the treatment with GCs on short- to mid-term, followed by TMX in the long term, were evaluated. Results: The mean age at diagnosis was 40.5 ± 6.8 years; female predominance was observed (F/M:7/1). Parameters related to IgG4-RD, like increase in IgG4 serum levels, total plasmablast counts, and IgG4+ plasmablasts, were negative in most of our patients in both active and inactive states of the disease. Likewise, an increased ratio of IgG4/IgG-positive plasma cells >40% could only be observed in 2 cases. GCs followed by TMX were given to the patients with an over-all median follow-up time of 67 (8–216) months. All the patients considerably improved clinically and had a reduction in the size of the mass lesion on GCs, followed by TMX therapy. None of the patients had a recurrence under TMX therapy for a median period of 18.5 (7–96) months. Conclusion: Even though RT is suggested to be a member of IgG4-RD, serologic or histological evidence of IgG4 elevation or positivity is only useful for diagnosis and follow-up of RT. The diagnosis should be based on clinical and radiological evidence and confirmed by histopathology. GCs are effective for initial treatment, and TMX is a successful and safe therapeutic option for long-term maintenance therapy.