Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe their production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE specific to receptor binding domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those immunized with two doses of CoronaVac; however, after boosting with BNT162b2, all groups presented similar IgE levels. IgE showed intermediate-to-high avidity, especially after the booster vaccine. We also found IgG4 antibodies, mainly after the booster, and they moderately correlated with IgE. ELISA results were confirmed by control assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We advocate for further research on IgE and its role in viral immunity, extending beyond allergies and parasitic infections.

OBJECTIVE: Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer.
METHODS: A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms \'autoimmune pancreatitis\' and \'pancreatic resection\' and supplemented by manual checks of reference lists in all retrieved articles.
RESULTS: Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients).
CONCLUSIONS: Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.

OBJECTIVE: The objective of this study was to examine the imaging features of hepatic inflammatory pseudotumors (IPTs) associated with IgG4-related and IgG4-unrelated conditions and to enhance the approach toward distinguishing between these two types of IPTs.
METHODS: A retrospective study was conducted, involving 20 patients diagnosed with hepatic IPTs. Imaging procedures were conducted within a timeframe of 4 weeks prior to hepatectomy or biopsy. The imaging features were then analyzed and compared using chi-squared analysis.
RESULTS: Seventeen (81.0%) IPTs were located in the hepatic subcapsular area; six (66.7%) IgG4-related IPTs were distributed around the hepatic hilum; and eleven (91.7%) IgG4-unrelated and three (33.3%) IgG4-related IPTs had unclear boundaries. All lesions exhibited similar characteristics in CT scans, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI), with the apparent diffusion coefficient (ADC) values slightly higher than the surrounding liver tissue. Delayed hypoenhancement, observed in five cases (55.6%), was exclusively present in IgG4-related IPTs. The remaining IPT lesions displayed progressive enhancement, septal and marginal enhancement, and persistent enhancement. Central enhancement was absent in three IgG4-related IPTs (33.3%) and ten IgG4-unrelated IPTs (83.3%). The duct-penetrating sign was identified in two IgG4-unrelated IPTs (16.7%) and seven IgG4-related IPTs (77.8%). Furthermore, seven patients with IgG4-related IPTs had additional lesions outside the liver.
CONCLUSIONS: IgG4-related lesions are frequently found in the vicinity of the hepatic hilum; they display the duct-penetrating sign and affect other organs as well. Both groups exhibited progressive or persistent contrast enhancement in typical IPT lesions, but delayed hypoenhancement was only observed in the IgG4-related IPT group. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement.
UNASSIGNED: Differences in imaging features differentiate IgG4-related and -unrelated inflammatory pseudotumors (IPT). IgG4-related lesions are frequently near the hepatic hilum, display duct-penetrating sign, and affect other organs. Only the IgG4-related group demonstrated delayed hypoenhancement. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement.
CONCLUSIONS: Compared with IgG 4-unrelated IPTs, IgG4-related IPTs show delayed hypoenhancement and affect other organs. IgG4-unrelated IPTs have unclear boundaries and lack central enhancement. Improved IPT diagnostic capabilities can help minimize additional, potentially unnecessary, interventions.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

Idiopathic granulomatous mastitis (IGM) is a benign, chronic inflammatory lesion of the breast. Immunoglobulin G4 (IgG4) associated disease is rare in the breast. In our study, we aimed to evaluate the efficacy of steroid treatment on IgG4 levels in tissue in patients diagnosed with IGM. Between 2008 and 2017, 55 patients diagnosed with IGM in our clinic were included in the study. Demographic, clinical, microbiologic and histopathologic characteristics, treatment modality and recovery time were evaluated retrospectively. Patients were divided into 3 groups according to tissue IgG4 levels: negative (Group I), infrequently and slightly positive (Group II), and highly positive (Group III). Group I patients had a complete response rate of 77.8%. In the rest of the patients (22.2%), insufficient response was detected from the beginning of the treatment. In Group II, the response rate was 91.3% and the permanent success rate after treatment was 87.0%. Although group III patients had a complete response at the beginning (95.65%), they relapsed in a short period of time (26.1%) after discontinuation of steroid treatment. At least one steroid-related side effect was observed in 47 (85.8%) patients in all groups. There is no consensus on the dose and duration of immunosuppressive treatment in IGM. In this study, responses to steroid treatment according to IgG4 concentration in pathologic breast tissue and recurrences after the end of treatment were determined. We think that high IgG4 concentration in the tissue is associated with recurrence and other immunosuppressive drugs should be added as maintenance after steroid treatment.

The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker has still not been found.
OBJECTIVE: We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition.
METHODS: Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated.
RESULTS: In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages.
CONCLUSIONS: The activation of the lectin-complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease.

IgG4-related disease is an immune-mediated fibroinflammatory condition. Isolated manifestation in the spine as hypertrophic pachymeningitis is very rare and the mass-like lesion on MRI often mimic tumour or infection. Patients would present with symptoms that result from mass effect or neurovascular compression. Studies showed that serum and CSF IgG4 levels are rarely informative, and therefore, tissue biopsy is crucial for accurate diagnosis. Apart from supporting the diagnosis, MRI is helpful in delineating the extent of disease and follow-up after treatment. A 18F-FDG PET/CT scan is useful in detecting systemic manifestations of IgG4-related disease. Although IgG4-related disease generally responds well to corticosteroid at inflammatory state, relapse is not uncommon. Current treatment strategies for IgG4-related hypertrophic pachymeningitis are high dose corticosteroid therapy and early decompressive surgery to avoid chronic neurological complications. We described a case of a 27-year-old gentleman complaining of lower limb weakness and numbness. MRI showed a mass-like epidural lesion at the thoracic spine causing cord compression. Open biopsy of the epidural mass demonstrated histopathological characteristics of IgG4-related disease. Patient responded well to early surgical decompression of the spinal cord and corticosteroid as evidenced by symptom improvement and resolving mass on subsequent MRI study. However, a follow-up MRI revealed disease recurrence years later.

UNASSIGNED: Immunoglobulin 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.
UNASSIGNED: A 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.
UNASSIGNED: It 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.

UNASSIGNED: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.
UNASSIGNED: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.
UNASSIGNED: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.
UNASSIGNED: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

Immunoglobulin G4-related disease is an immune-mediated condition comprised of a number of various disorders sharing unique pathologic, serologic, and clinical features. Diagnosis of immunoglobulin G4-related sclerosing mastitis is challenging as the clinical and imaging findings mimic breast malignancies or other types of inflammatory mastitis. Herein, we describe a case of a female patient with a painless palpable mass in her right breast. An excisional core biopsy led to the rare diagnosis of immunoglobulin G4-related sclerosing mastitis, and the patient received steroid treatment for a month. To date, the patient has remained disease-free without any recurrence. As immunoglobulin G4-related sclerosing mastitis is a very rare disease, further studies are needed to reach conclusions about the pathogenesis, diagnosis, and treatment of this entity.