Elevated Immunoglobulin G4 Levels Research Articles

7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH. Presentation: 6/1/2024

Therapeutic Potential of Salvia miltiorrhiza Root Extract in Alleviating Cold-Induced Immunosuppression.

The interaction between environmental stressors, such as cold exposure, and immune function significantly impacts human health. Research on effective therapeutic strategies to combat cold-induced immunosuppression is limited, despite its importance. In this study, we aim to investigate whether traditional herbal medicine can counteract cold-induced immunosuppression. We previously demonstrated that cold exposure elevated immunoglobulin G (IgG) levels in mice, similar to the effects of intravenous immunoglobulin (IVIg) treatments. This cold-induced rise in circulating IgG was mediated by the renin-angiotensin-aldosterone system and linked to vascular constriction. In our mouse model, the cold-exposed groups (4 °C) showed significantly elevated plasma IgG levels and reduced bacterial clearance compared with the control groups maintained at room temperature (25 °C), both indicative of immunosuppression. Using this model, with 234 mice divided into groups of 6, we investigated the potential of tanshinone IIA, an active compound in Salvia miltiorrhiza ethanolic root extract (SMERE), in alleviating cold-induced immunosuppression. Tanshinone IIA and SMERE treatments effectively normalized elevated plasma IgG levels and significantly improved bacterial clearance impaired by cold exposure compared with control groups injected with a vehicle control, dimethyl sulfoxide. Notably, bacterial clearance, which was impaired by cold exposure, showed an approximately 50% improvement following treatment, restoring immune function to levels comparable to those observed under normal temperature conditions (25 °C, p < 0.05). These findings highlight the therapeutic potential of traditional herbal medicine in counteracting cold-induced immune dysregulation, offering valuable insights for future strategies aimed at modulating immune function in cold environments. Further research could focus on isolating tanshinone IIA and compounds present in SMERE to evaluate their specific roles in mitigating cold-induced immunosuppression.

Clinical characteristics and treatment outcomes of patients with IgG4-positive ocular adnexal marginal zone B-cell lymphoma.

To explore the clinicopathological characteristics of immunoglobulin G4 (IgG4)-positive ocular adnexal marginal zone B-cell lymphoma (OAML) and associated patient treatment outcomes. Medical records from patients diagnosed with IgG4-positive OAML treated at the West China Hospital between January 2016 and August 2023 were retrospectively analyzed. This study included data from 22 patients (11 males, 11 females), aged between 36 and 83 years, with disease durations from 1 month to 30 years. Sixteen cases exhibited unilateral ocular involvement (ten left eyes, six right eyes), while six exhibited bilateral involvement. Common clinical symptoms included ocular masses, eyelid swelling, and proptosis, with the orbit and lacrimal gland being the most commonly impacted sites. Among the 22 patients, 13 who were clinically suspected of having IgG4-related ophthalmic disease (IgG4-ROD) underwent serum IgG4 testing pre-operatively, revealing elevated IgG4 levels in 11 of these patients. The use of computed tomography and magnetic resonance imaging facilitated the evaluation of the location and size of lesions. All 22 patients received surgical treatment. Subsequently, 14 of these patients underwent local radiotherapy, five received post-operative chemotherapy, and three were closely observed. The follow-up period of patients in this study was 3-77 months, with an average follow-up time of 36 months. Except for one patient who died of disease progression, all others showed favorable prognoses with significant improvements. These results support the classification of IgG4-positive OAML as a distinct OAML sub-type with clinical features that partially overlap with IgG4-ROD. Therefore, accurate differentiation between OAML and IgG4-ROD is imperative, necessitating timely surgical intervention and precise pathological diagnosis to prevent diagnostic errors and inappropriate treatment. Currently, no standardized treatments for IgG4-positive OAML exist, but our results suggest that standard OAML therapies are generally efficacious.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

Add-on immunosuppressive therapy may benefit selected patients with primary biliary cholangitis and autoimmune phenomena.

Mildly elevated levels of transaminase and/or immunoglobulin G (IgG) are common in patients with primary biliary cholangitis (PBC). It is still unclear whether adding immunosuppressive therapy to ursodeoxycholic acid (UDCA) benefits those patients who are not fulfilling the diagnostic criteria of PBC with autoimmune hepatitis (AIH) features. To assess the efficacy of adding immunosuppressive therapy to UDCA for patients with PBC and autoimmune phenomena but not fulfilling the diagnostic criteria of PBC with AIH features. This is a retrospective-prospective cohort study in a tertiary medical center. Patients with PBC and autoimmune phenomena were defined by the elevation of IgG and/or transaminase but did not fulfill the diagnostic criteria of PBC with AIH features. We grouped these patients based on with and without add-on immunosuppressive therapy and balanced their baseline characteristics using inverse probability treatment weighting (IPTW). A total of 652 patients with PBC and autoimmune phenomena were included, with a median follow-up of 4.08 years. After IPTW, the pseudo sample size in the add-on therapy and monotherapy groups was 558 and 655, respectively. After 1 year of observation, patients in the add-on therapy group had a higher biochemical response rate (normalization of transaminase and IgG levels) (49% versus 17%, p < 0.001). Furthermore, add-on therapy improved the transplant-free survival in the subgroup of patients with PBC and transaminase ⩾3 × upper limit of normal (ULN) or IgG ⩾1.3 × ULN (p = 0.033). Add-on immunosuppressive therapy may improve the normalization rates of transaminase and IgG levels in all patients with PBC and mildly elevated transaminase and IgG levels and the long-term outcomes in the subgroup of the patients with transaminase ⩾3 × ULN or IgG ⩾1.3 × ULN.

Therapeutic Uses of Rituximab and Clinical Features in Immunoglobulin G4-Related Disease: A Systematic Review.

This research presents a systematic review focusing on rituximab's therapeutic applications in immunoglobulin G4 (IgG4)-related disease (IgG4-RD), a rare condition characterized by immune-mediated systemic inflammation and tissue fibrosis, as well as the clinical features of IgG4-RD. While the disease commonly affects organs such as the bile ducts, lymph nodes, retroperitoneum, pancreas, and salivary glands, it can potentially involve other organs. This intricacy often leads to diagnostic challenges due to clinical overlaps with cancer, infections, and other autoimmune disorders. The diagnosis of IgG4-RD necessitates a comprehensive approach involving laboratory tests, imaging studies, and clinical assessments. Symptoms can vary, ranging from lymphadenopathy to jaundice, affecting multiple organs. Although elevated blood IgG4 levels and findings of tissue involvement and fibrosis on imaging can be suggestive, they lack the specificity for a definitive diagnosis. Early diagnosis is crucial for initiating corticosteroids and immunosuppressive to prevent further damage from IgG4-RD. This study highlights the therapeutic role of rituximab in managing this condition. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, the research identifies and evaluates relevant literature across various electronic databases, including PubMed, ScienceDirect, and Google Scholar. This review includes 14 selected publications, comprising three systematic reviews, three observational studies, four narrative reviews, and four case reports. The study design ensures a comprehensive evaluation of rituximab's potential efficacy in treating IgG4-RD and its associated clinical characteristics. Based on this study, it can be concluded that IgG4-RD can potentially be treated with rituximab, particularly in cases of relapse and maintaining remission.

Hepatic Involvement of Diffuse Large B-Cell Lymphoma Mimicking Antinuclear Antibody-Negative Autoimmune Hepatitis Diagnosed by Liver Biopsy

Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy.

Multi-color imaging in a unilateral central retinal artery occlusion following dengue fever: A case report and literature review

Background: Dengue fever is associated with various sight-threatening ocular manifestations, some of which can occur several months after fever. These include subconjunctival hemorrhage, vitreous hemorrhage, retinal hemorrhage, cotton wool spots, central and branch retinal artery occlusion, central scotoma, papilledema, optic neuropathy, retinal vasculitis, retinitis, retinal pigment epithelium mottling, foveolitis, choroidal effusion, exudative retinal detachment, anterior uveitis, endogenous endophthalmitis, and panophthalmitis. Herein, we report a patient with unilateral central retinal artery occlusion (CRAO) and raised dengue immunoglobulin G (IgG) titers who underwent serial multimodal imaging with fundus photography, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCTA), and multi-color imaging (MCI). Furthermore, we reviewed recent publications highlighting different eye diseases and the role of MCI in their diagnosis and serial monitoring.&#x0D; Case presentation: A 53-year-old Asian Indian woman complained of blurring of vision in the right eye (OD) two months after a bout of fever. Her best-corrected distance visual acuity was finger counting close to the face in the OD and 20/40 in the left eye. CRAO of the OD was diagnosed. Systemic investigations were normal except for elevated dengue IgG levels. Optical coherence tomography and fluorescein angiography confirmed this diagnosis. MCI and SD-OCT using Spectralis™ performed before and after treatment with oral steroids demonstrated improvement. MCI served as a noninvasive ancillary tool for monitoring the CRAO. In addition to the case report, we summarize articles pertaining to MCI published during the years 2018–2022. The list is not exhaustive but highlights salient features of different retinal and choroidal disorders evaluated using MCI. Our summary highlights the role of MCI in the diagnosis and serial monitoring of eye diseases.&#x0D; Conclusions: A diagnosis of post-dengue fever retinal artery occlusion should be made after ruling out other causes of retinal artery vascular occlusion. We demonstrated retinal changes using serial imaging. MCI can be a useful tool, along with SD-OCT, to monitor clinical improvement. Optometrists can follow up patients with retinal vascular occlusions using noninvasive methods.

Immunoglobulin G4-related endocrine diseases

Immunoglobulin G4-related disease has become the focus of interest in recent years. The disease is characterized by inflammation of the organs involved, often with a macroscopic appearance suggestive of a tumor, elevated immuno-globulin G4 levels, immunoglobulin G4-positive plasma cell infiltration on histological examination, fibrosis, oblit-erative phlebitis, and typically a rapid therapeutic response to corticosteroids. The disease can show a variety of organ manifestations, with frequent involvement of exocrine glands. Among the endocrine organs, symptoms may appear in the thyroid gland and the pituitary gland. The criteria for immunoglobulin G4-related hypophysitis were formu-lated in 2011. Until a few years ago, a condition formerly known as Riedel's thyroiditis was identified as immuno-globulin G4-related thyroiditis. Based on the criteria system for immunoglobulin G4-related thyroid diseases pub-lished in 2021, some patients with Hashimoto's thyroiditis and Graves' disease can also be classified as immunoglobulin G4-related thyroid disease. The identification of immunoglobulin G4-related endocrine diseases and the establishment of an accurate diagnosis can modify the treatment of the patient and determine the course of the disease. Other organ manifestations should be sought in patients with immunoglobulin G4-related endocrine disease and lifelong immunological follow-up is warranted.

Congenital Human Cytomegalovirus Infection Is Associated With Decreased Transplacental IgG Transfer Efficiency Due to Maternal Hypergammaglobulinemia.

Placentally transferred maternal immunoglobulin G (IgG) protects against pathogens in early life, yet vertically transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored. We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a US-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive nontransmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year. Transplacental IgG transfer efficiency was decreased by 23% (95% confidence interval [CI] 10-36%, P = .0079) in cCMV-infected pairs and 75% of this effect (95% CI 28-174%, P = .0085) was mediated by elevated maternal IgG levels (ie, hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection. Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer.

Immunoglobulin G food testing

Patients often present to allergy clinics with a history of diverse, multisystem symptoms. Convinced that they have food allergies, they seek testing and evaluation. However, many patients present to the clinic having already completed commercially available food allergy or sensitivity tests that have become commonplace in popular media. Most of these tests are immunoglobulin G (IgG) food panel testing, with up to 100 foods evaluated with a single test. The companies claim to diagnose food sensitivities or intolerances based solely on elevated IgG levels to foods.

Elevated Serum IgG4 Was Found in Eosinophilic Granulomatosis With Polyangiitis.

The aim was to determine the levels and clinical impact of immunoglobulin G4 (IgG4) and other IgG subclasses in a Chinese population with eosinophilic granulomatosis with polyangiitis (EGPA). We enrolled 49 patients who had EGPA, 27 who had granulomatosis with polyangiitis (GPA), 31 who had microscopic polyangiitis (MPA), and 30 healthy controls (HCs). Serum IgG subclasses were measured using commercial immunonephelometric assays and compared among different groups. Fifteen EGPA patients (30.61%) had elevated IgG4 levels, based on a cutoff value of 135 mg/dL. In addition, 2 GPA patients (7.40%) and 1 MPA patient (3.33%) had elevated IgG4 levels. The EPGA group had a higher IgG4 level (65.60 mg/dL) than the GPA group (32.70 mg/dL, p = 0.0021), the MPA group (30 mg/dL, p = 0.0021), and the HC group (28.55 mg/dL, p = 0.0002). The EPGA group also had a higher IgG4/IgG ratio (0.0644) than the GPA group (0.0322, p = 0.13), the MPA group (0.0289, p = 0.0055), and the HC group (0.0212, p < 0.0001). Our results indicate that Chinese patients with EGPA have increased levels of serum IgG4. Further study is needed to determine the pathogenic role of IgG4 and IgG4 antineutrophil cytoplasmic antibodies in EGPA.

Pancreatic solid focal lesions: autoimmune pancreatitis or pancreatic cancer?

Purpose: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) in treatable early stages continues to be challenging. Autoimmune pancreatitis (AIP) can, similarly to PDAC, present as a focal mass and, therefore, an accurate differential diagnosis is of crucial importance. Raised serum immunoglobulin G4 (IgG4) levels, over the twice the normal value, are considered to be one of the significant diagnostic features of type 1 AIP. However, IgG4 can also be increased in patients with PDAC, but levels usually do not exceed twice the normal value. Materials and methods: In the years 2012 - 2018, IgG4 serum levels were examined in 117 patients with histologically confirmed PDAC. Histological resection specimens or bioptic specimens were taken from the pancreatic lesions of patients with both PDAC and an elevated IgG4 level (above 135mg/dL). These were then tested for the presence of IgG4 and plasmocytes in the pancreatic tissue, and changes characteristic for type 1 AIP were also searched for. Results: In 14/117 PDAC patients (11.9 %) the plasmatic IgG4 levels were higher than 135 mg/dL. In 2 patients (1.7 %) the serum IgG4 levels were more than double the normal value, and thus suggestive of AIP according to the guidelines. Of these two patients - one of them met the histological criteria for diagnosis of AIP in the simultaneous presence of PDAC. Conclusions: Differentiating AIP from PDAC can be sometimes problematic since these diseases can both present as focal pancreatic mass/ lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as is the case with PDAC. IgG4 levels of over the twice of the upper limit are rare among PDAC patients (1.7% in our study group). However, cases of simultaneous presentation of PDAC and AIP have been documented and should not be neglected. Therefore, targeted biopsy of the pancreas is the method of choice in cases suspected of being a focal form of AIP, and we recommend it over other modalities, such as e.g. response to steroid therapy.

Clinical and imaging findings suggestive of histopathological immunoglobulin G4-related disease: a single-center retrospective study.

To investigate the clinical and imaging features predicting the histopathological diagnosis of immunoglobulin G4 (IgG4)-related disease (IgG4RD) in patients with suspected IgG4RD on computed tomography (CT). We retrospectively reviewed the medical records of 178 patients with CT findings suspicious of IgG4RD from January 2015 to December 2017. Patients who underwent tissue biopsy were included to evaluate the association between patient characteristics and histopathological diagnosis of IgG4RD. The histopathological diagnosis was classified into IgG4RD and non-IgG4RD. Clinical, laboratory, and imaging features were compared between patients with IgG4RD and non-IgG4RD, and logistic regression analysis was performed to identify the predictors for histopathologically confirmed IgG4RD. Of the 103 patients with histopathologically proven diseases, 46 and 57 patients were classified as IgG4RD and non-IgG4RD, respectively. The median age was 64 years; 65% of patients were male. There were significant differences in sex (P = 0.035), fever (P = 0.039), serum IgG4 level (P < 0.001), renal involvement (P = 0.036), lacrimal or salivary glands involvement (P = 0.050), swelling pattern on CT (P = 0.001), and positron emission tomography (PET)-CT findings (P < 0.001) between patients with IgG4RD and non-IgG4RD. Multivariate analysis revealed elevated IgG4 level > 135 mg/dL (odds ratio [OR] = 5.418, P < 0.001), kidney involvement (OR = 6.170, P = 0.044), and the swelling feature on CT (OR = 4.301, P = 0.012) to be independent factors for histopathological diagnosis of IgG4RD. This study suggests that elevated IgG4 level, renal involvement, and swelling pattern on CT are associated with histopathological diagnosis of IgG4RD. The clinical and imaging features might help to decide further evaluation in patients with clinically suspected IgG4RD. Key Points • Computed tomography (CT) is not sufficient to discriminate between IgG4-related disease (IgG4RD) and non-IgG4RD conditions. • Histopathological diagnosis of IgG4RD is associated with elevated IgG4 level, renal involvement, and swelling pattern on CT. • Positron emission tomography-CT may be a useful diagnostic tool in patients with clinically suspected IgG4RD. >.

Elevated Immunoglobulin G4 Levels in Patients with Thyroid Eye Disease and Their Clinical Implications.

PurposeThe purpose of this study was to assess the relationship between thyroid eye disease (TED) in patients undergoing orbital decompression and immunoglobulin G4 (IgG4) levels.MethodsA prospective observational cohort study was conducted among 185 consecutive patients who were diagnosed with TED and underwent orbital decompression. Serum levels of IgG4 were measured, and immunohistochemical staining for IgG and IgG4 was performed in orbital adipose tissue. Data related to clinicopathologic features were analyzed.ResultsAmong the 185 enrolled patients with TED, 64 (34.6%) were IgG4-positive. The IgG4-positive patients were older, had higher clinical activity scores (CAS), and had worse best-corrected visual acuity (BCVA) than the IgG4-negative patients. Higher thyrotropin receptor antibody (TRAb) levels, histopathological IgG4 counts, IgG4/IgG ratios, and dense lymphocyte infiltration were more frequently observed in IgG4-positive than in IgG4-negative patients. Definitive and probable IgG4 subtypes were independently associated with the active stage in patients with TED.ConclusionsOur data suggest that the IgG4 subtype in TED is common. IgG4-positive patients with TED may be older, have more severe disease, and have higher clinical activity scores. IgG4 may play an important role in the pathogenesis of TED.

Characteristics of patients with primary Sjögren's syndrome associated interstitial lung disease and relevant features of disease progression.

To investigate characteristics of patients with primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD) and relevant features of ILD progression. Patients with pSS were retrospectively reviewed, and pSS-ILD and pSS non-ILD were identified. Clinical data, laboratory parameters, pulmonary high-resolution CT (HRCT), and pulmonary function tests (PFTs) were collected. pSS-ILD patients were further categorized into subgroups according to HRCT patterns or PFTs. Eighty-five pSS-ILD patients and 85 pSS non-ILD patients were included. The average age at disease onset and median disease duration were significantly higher in pSS-ILD patients than those in pSS non-ILD patients (p < 0.001). Fever, xerostomia, xerophthalmia, and numbness were more frequent, and white blood cells, C reactive protein, and immunoglobulin G (IgG) levels were higher in pSS-ILD patients when compared to pSS non-ILD patients (p < 0.01). More male patients, older age at disease onset, and less frequent anti-Ro52 antibody were noted in patients with CT-usual interstitial pneumonia (UIP) pattern. In 49 patients with pSS-ILD, who repeated PFTs 6months from the baseline, 79.6% were stable while 20.4% progressed, with ESR and CT-UIP pattern related with disease progression. Patients with pSS-ILD were characterized by more frequent fever, xerophthalmia, and elevated IgG levels, while male, older age at disease onset, and less frequent anti-Ro52 antibody were related with CT-UIP pattern. ESR and CT-UIP pattern were potential predictors for ILD progression.Key Points• pSS-ILD patients are characterized by more frequent fever, xerophthalmia and elevated IgG.• Anti-Ro52 antibody is less frequent in patients with CT-UIP pattern compared to non-UIP patterns.• ESR and CT-UIP pattern are associated with pSS-ILD progression.

Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls.

BackgroundCytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.MethodsA total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured.ResultsCMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population.ConclusionsCMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.

Association between serum IgG level and clinical course in primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis is a chronic cholestatic liver disease. The pathomechanism is still not fully understood, but there is evidence that immune-mediated processes may contribute to disease progression.MethodsWe studied the prognostic relevance of serum immunoglobulin G (IgG) elevated above the upper limit of normal as a marker for immune activation at initial diagnosis and its influence on transplantation-free survival in a well-defined cohort of PSC patients.ResultsThe final study cohort comprises of 148 PSC patients. Elevated IgG levels were found in 66 patients (44.6%). Apart from their younger age at first diagnosis, there was no significant difference between patients with or without elevated IgG levels. The presence of a concomitant inflammatory bowel disease, an autoimmune hepatitis or immunosuppressive medication was equally distributed between both groups. Patients with elevated IgG levels reached the combined endpoint (34 (59.6%) vs. 23 (40.4%); p = 0.004) significantly more often and had reduced transplantation-free survival (Log-rank: 24.0 (10.2–37.9) vs. 14.0 (8.5–19.5); p < 0.05). Cox regression analysis including age, gender, presence of IBD, presence of dominant stricture (DS), Mayo Risk Score (MRS), immunosuppression, biochemical response to UDCA and elevated IgG-levels confirmed MRS (p = 0.03), DS (p = 0.04), biochemical response (p = 0.04) and elevated IgG level (p = 0.04) as independent risk factors for reduced transplantation-free survival.ConclusionWe identified elevated serum IgG levels at first diagnosis as an independent risk factor for reduced transplant free-survival in patients with PSC.

Higher frequency of false-positive serum galactomannan tests among older subjects and the association with elevated serum immunoglobulin G levels.

The incidence of false-positive serum galactomannan (GM) enzyme-linked immunosorbent assay test results has been scarcely examined among older subjects. Additionally, previous studies have highlighted the influence of serum immunoglobulin G (IgG) levels on GM test results. We hypothesised that age-related IgG level elevation might also be associated with false-positive GM test results in older subjects. This study aimed to examine the association between false-positive GM test results and age or serum IgG levels. We investigated the association between false-positive serum GM test results and age in 1071 healthy adult subjects. Then, we validated this association and further explored the correlation with serum IgG levels by retrospectively identifying 700 patients with newly diagnosed haematologic disorders without probable or proven invasive aspergillosis. Healthy subjects with false-positive GM test results were significantly older than those without false-positive results (P<0.001). Among patients with haematologic disorders, IgG myeloma patients showed significantly higher false-positive rates (57/125 [45.6%]) than patients with other haematologic disorders (non-Hodgkin lymphoma: 48/315 [15.2%], myelodysplastic syndrome/aplastic anaemia: 19/141 [13.5%]; both P<0.001) or other types of myeloma (IgA myeloma: 13/60 [21.7%], light chain myeloma: 9/52 [17.3%]; both P<0.01). Furthermore, among non-multiple myeloma patients, advanced age and higher IgG level were also significantly associated with the high frequency of false-positive GM test results. False-positive serum GM test results were frequent among older subjects and patients with elevated serum IgG levels. These results suggested that age- and/or disease-related IgG level elevation could induce this phenomenon.

Pancreatic Solid Focal Lesions: Differential Diagnosis between Autoimmune Pancreatitis and Pancreatic Cancer

Background: Diagnosis of pancreatic cancer (PC) in early stages is still challenging for gastroenterologists. The early detection of cancer is one of the utmost importance for the successful therapy of this malignancy. An accurate differential diagnosis of focal pancreatic lesions plays also an important role, whether it is differential diagnosis of chronic pancreatitis from PC or autoimmune pancreatitis (AIP) from PC. Raised serum immunoglobulin G4 (IgG4) levels to twice the normal value are considered one of significant diagnostic features of type 1 AIP. However, IgG4 can be increased also in patients with PC, but levels usually do not exceed twice the normal value. Methods: In years 2012–2017, IgG4 serum levels were examined in 115 patients with histologically confirmed PC. Patients with PC and elevated IgG4 level (above 135 mg/dL) had tested their histological resection specimens or bioptic specimens from pancreatic lesion, with targeted detection of the presence of IgG4 and plasmocytes in the pancreatic tissue and changes characteristic for type 1 AIP. Results: A plasmatic IgG4 level in 115 patients with diagnosed PC was higher than 135 mg/dL in 14 patients (12.2%). Out of them, 2 patients (1.7%) revealed a serum IgG4 level higher than double the normal value, that is, higher than 270.0 mg/dL (suggestive of AIP). One patient met histological criteria for diagnosis of AIP in the simultaneous presence of PC. Conclusion: Diagnosis of early cancer stages, particularly differentiating AIP from PC can be sometimes problematic. IgG4 levels can be slightly elevated also in case of PC. A targeted biopsy of the pancreas is the method of choice in cases suspected from a focal form of AIP and we recommend to prefer it over other modalities, such as, for example, response to steroid therapy.