Immunoglobulin G4 related pancreatitis; can it be a rare cause of secondary diabetes?

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)—characterized as tumors mimicking malignant orbital lymphoma (OL)—responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions—involving both lacrimal glands on CT scans—higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674–1.000, p = 0.005] vs. 0.766 [95% CI: 0.615–0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518–0.997] vs. 0.75 [95% CI: 0.509–0.913]), higher specificity (0.813 [95% CI: 0.544–0.960] vs. 0.778 [95% CI: 0.578–0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

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Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22084083 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4083

Author(s):

Asami Nishikori ◽

Yoshito Nishimura ◽

Rei Shibata ◽

Koh-ichi Ohshima ◽

Yuka Gion ◽

...

Keyword(s):

Marginal Zone ◽

Somatic Hypermutation ◽

Cytidine Deaminase ◽

Marginal Zone Lymphoma ◽

Immunoglobulin G4 ◽

Intensity Index ◽

Activation Induced Cytidine Deaminase ◽

Systemic Disorder ◽

Lymphoplasmacytic Infiltration ◽

Ophthalmic Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

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Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa

Biomedicines ◽

10.3390/biomedicines9060621 ◽

2021 ◽

Vol 9 (6) ◽

pp. 621

Author(s):

Aurélien Millet ◽

Nihel Khoudour ◽

Jérôme Guitton ◽

Dorothée Lebert ◽

François Goldwasser ◽

...

Keyword(s):

Mass Spectrometry ◽

Human Plasma ◽

High Resolution Mass Spectrometry ◽

Internal Standard ◽

Therapeutic Drug ◽

Limit Of Quantification ◽

Immunoglobulin G4 ◽

Positive Mode ◽

Surrogate Peptide ◽

First Time

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine 13C6-15N4 and Lysine 13C6-15N2) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. The assay showed good linearity over the range of 1–100 μg/mL, a limit of quantification at 1 μg/mL, excellent accuracy from 4.4% to 5.1%, and also a between-day precision below 20% at the limit of quantification. In parallel, an in-house ELISA was developed with a linearity range from 2.5 to 50 µg/mL. Then, results were obtained from 70 plasma samples of cancer patients that were treated with pembrolizumab and quantified with both methods were compared using the Passing-Bablok regression analysis and Bland-Altman plotting. The LC-MS/HRMS method is easy to implement in the laboratory for use in the context of PK/PD studies, clinical trials, or therapeutic drug monitoring.

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A Case of IgG4-Related Kidney Disease Developing While on Steroid Treatment for Autoimmune IgG4 Pancreatitis

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211026500 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110265

Author(s):

Jonathan Vincent M. Reyes ◽

Dawn Maldonado ◽

Aaron S. Stern ◽

Maritza Brown

Keyword(s):

Kidney Disease ◽

Inflammatory Process ◽

Systemic Disease ◽

Multiple Organ ◽

Steroid Treatment ◽

Autoimmune Process ◽

Immunoglobulin G4 ◽

Organ Systems ◽

The Relationship ◽

Steroid Sparing

IgG4 (immunoglobulin G4)-related systemic disease is an autoimmune process affecting multiple organ systems. This inflammatory process can present as but not limited to pancreatitis, cholangitis, or unspecified kidney disease. In this case, our patient developed IgG4-related kidney disease while already on a prolonged steroid course for IgG4-related pancreatitis. The patient ultimately had renal recovery after starting a higher dose of prednisone, but also developed steroid-related complications. This case further highlights the relationship between IgG4 diseases now termed IgG4-related systemic disease. This case brings to light the need for further investigative research into ideal steroid dosing, as well as steroid-sparing agents for IgG4-related systemic disease.

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Immunoglobulin G4-related masses surrounding coronary arteries: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab055 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Takuya Nakamura ◽

Yutaka Goryo ◽

Takuya Isojima ◽

Hiroyuki Kawata

Keyword(s):

Coronary Artery ◽

Coronary Angiography ◽

Cardiovascular System ◽

Coronary Arteries ◽

Elevated Serum ◽

High Serum ◽

Immunoglobulin G4 ◽

Coronary Arteritis ◽

Serum Igg4 ◽

Mass Formation

Abstract Background Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with high serum IgG4 levels affecting various organs, such as the pancreas, lacrimal and salivary glands, thyroid, kidney, and lung. Typical cardiovascular manifestations of IgG4-RD include periaortitis, coronary arteritis, and pericarditis. However, reports of IgG4-RD associated with coronary arteritis are rare. Here, we report a case of IgG4-related masses surrounding the coronary arteries. Case summary A 59-year-old man was referred to our hospital because of mediastinal masses detected by computed tomography (CT). Coronary CT angiography revealed masses surrounding the right coronary artery and the left anterior descending coronary artery. An elevated serum level of IgG4 and histological findings led to the diagnosis of IgG4-related coronary arteritis with mass formation. Coronary angiography showed numerous feeding arteries to the masses, which were demonstrated as multiple microchannels in the intravascular ultrasound (IVUS) images. Discussion IgG4-RD involving the cardiovascular system has been reported. However, coronary artery disease associated with IgG4-RD is very rare, and the mechanism of mass formation in IgG4-related coronary arteritis is unclear. In our case, within the cardiovascular system, IgG4-RD was limited to the coronary arteries, suggesting that the affected coronary arteries may provide the necessary blood supply to the mass, thus, aiding its growth. These findings were supported by the images from coronary angiography and IVUS.

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Immunoglobulin G4–related disease of the paratestis: Can we avoid radical treatment?

Journal of Clinical Urology ◽

10.1177/2051415820982778 ◽

2020 ◽

pp. 205141582098277

Author(s):

Thomas Thompson ◽

Thomas Brophy ◽

Mohsin Uddin ◽

James Bolton ◽

Richard Napier-Hemy

Keyword(s):

Immunoglobulin G4 ◽

Related Disease ◽

Radical Treatment

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