IgG4-associated Disease Research Articles

Treatment of retroperitoneal fibrosis with rituximab, cyclophosphamide and dexamethasone, followed by rituximab and dexamethasone maintenance, achieved disappearance of pathological PET accumulation of FDG and regression of fibrotic masses after 4 months….

Idiopathic retroperitoneal fibrosis is characterized by the development of inflammatory infiltrates with marked fibrosis along the large retroperitoneal vessels. Rituximab in combination with glucocorticoids constitute an effective therapy, but the responses are not long-lasting. In other similar situations, addition of cyclophosphamide to the combination achieved longer and deeper responses. This was the reason to use the triple combination in this case. A 56-year-old man came with four weeks lasting abdominal pain with CT finding of retroperitoneal fibrosis with unilateral ureteral occlusion. Biopsy confirmed retroperitoneal fibrosis with histological findings of IgG4-associated disease. Treatment with prednizone was poorly tolerated. Therefore, the patient was switched to the combination of rituximab 375 mg/m2 on day 1, cyclophosphamide 300 mg/m2 in infusion in days 1 and 15, plus dexamethasone 20 mg in infusion on days 1 and 15, repeated in a 28-day cycle. Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) examination after 4 months of treatment showed a marked decrease in FDG accumulation and complete disappearance of the fibrotic mass. After 8 months, the induction therapy was followed by maintenance therapy with rituximab 1,000 mg plus dexamethasone 20 mg in 6-month intervals. Control PET/MR examination after 3 years is consistent with complete remission. The number of circulating plasmablasts correlated with the disease activity. Treatment of retroperitoneal fibrosis with the tripple combination of rituximab, cyclophosphamide and dexamethasone achieved a very rapid disappearance of pathological FDG accumulation and fibrotic retroperitoneal mass, with complete disappearance achieved after 4 months of treatment. After 3 years of maitenance therapy, the diesease is still in complete remission on PET/MR examination. We suggest to continue the maintenance therapy with rituximab because of some increase in the number of circulating plasmablasts after prolongation of the intervals between rituximab administration.

The Role of Metal Nanoparticles in the Pathogenesis of Stone Formation.

The process of stone formation in the human body remains incompletely understood, which requires clinical and laboratory studies and the formulation of a new endogenous, nanotechnological concept of the mechanism of origin and formation of crystallization centers. Previously, the mechanism of sialolithiasis was considered a congenital disease associated with the pathology of the ducts in the structure of the glands themselves. To date, such morphological changes of congenital nature can be considered from the position of the intrauterine formation of endogenous bacterial infections complicated by the migration of antigenic structures initiating the formation of crystallization centers. The present work is devoted to the study of the morphology and composition of stones obtained as a result of surgical interventions for sialolithiasis. Presumably, nanoparticles of metals and other chemical compounds can be structural components of crystallization centers or incorporated into the conditions of chronic endogenous inflammation and the composition of antigenic structures, in complexes with protein and bacterial components. X-ray microtomography, X-ray fluorescence analysis, scanning transmission electron microscopy and microanalysis, mass spectrometry, and Raman spectroscopy were used to study the pathogenesis of stone formation. Immunoglobulins (Igs) of classes A and G, as well as nanoparticles of metals Pb, Fe, Cr, and Mo, were found in the internal structure of the stones. The complex of antigenic structures was an ovoid calcified layered matrix of polyvid microbial biofilms, with the inclusion of metal nanoparticles and chemical elements, as well as immunoglobulins. The obtained results of clinical and laboratory studies allow us to broaden the view on the pathogenesis of stone formation and suggest that the occurrence of the calcification of antigenic structures may be associated with the formation of IgG4-associated disease.

A rare deleterious case of concomitant renal disease associated with IgG4-associated systemic disease

In IgG4-associated disease, several organs and tissues are often affected, especially kidney tissue, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membra[1]nous nephropathy).IgG4-associated disease was isolated as an independent nosological form in 2003, when patients with type 1 autoimmune pancreatitis were found signs of systemic damage (involvement of the biliary tract, salivary glands, retroperitoneal space), and in 2012 the first international nomenclature of the disease was proposed.The clinical manifestations of IgG4-associated disease are nonspecific and diverse, which determines the difficulties of differential diagnosis, including infections and tumors, and increases the period from the onset of the disease to diagnosis to an average of 2 years. IgG4-associated disease is more likely to develop in middle age and old age. The prevalence of the disease is higher among men than among women. Thus, autoimmune pancreatitis type 1, retroperitoneal fibrosis and tubulointerstitial nephritis are more common in men, and sialoadenitis, dacryoadenitis and thyroiditis are more common in women.In this article, we present a clinical case of IgG4-associated systemic disease with a combined lesion of the tubulo-interstitial and glomerular compartments of kidney tissue with nephrotic syndrome as the only initial manifestation. The combination of IgG4-tubulo-interstitial nephritis with membranous nephropathy is an ex[1]tremely rare pathology. Nephrobiopsy was crucial in the diagnosis of this condition, which allowed the patient to be prescribed proper and timely treatment.

IgG4-associated disease and antineutrophil cytoplasmic antibodies-associated vasculitis overlap syndrome with renal involvement: diagnostic difficulties and treatment strategies.

IgG4-associated disease and antineutrophil cytoplasmic antibodies-associated vasculitis overlap syndrome with renal involvement: diagnostic difficulties and treatment strategies.

IgG4-associated disease with systemic lupus erythematosus: A case report and review.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Deciphering three predominant biopsy-proven phenotypes of IgG4-associated kidney disease: a retrospective study.

IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3g/d, group B 4.0g/d, group C 0.8g/d, P<0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45g/l, group B 119.60g/l, group C 87.94g/l, P<0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

КЛИНИЧЕСКИЙ СЛУЧАЙ IGG4-АССОЦИИРОВАННОГО ПАНКРЕАТИТА

Abstract. Introduction. IgG4-associated pancreatitis is a rare chronic autoimmune disease characterized by pancreas infiltration with IgG4 cells and by an increased IgG4 level in blood serum. Aim. Present a clinical case of IgG4-associated pancreatitis. Materials and Methods. A clinical case is presented, describing IgG4-associated pancreatitis in a 22-year- old male patient. Results and Discussion. During the examination, the following conditions were excluded: Autoimmune liver diseases (ANA, ASMA IgG, LKM-1 IgG – negative, according to liver elastography, fibrosis 0) and primary sclerosing cholangitis (based on magnetic resonance cholangiopancreatography). Pancreas dimensions were enlarged (according to computed tomography: 41.5x29x36.5 mm, smoothed lobulation; hepatosplenomegaly, intraperitoneal lymphadenopathy, and ascites minor). Against the treatment (Mesalazine, Ferrum Lek, and prednisolone 60 mg intravenously, with a transition of 50 mg per day inside), positive changes were noticed (body temperature normalized, daily stool frequency decreased). Conclusions. The case presented demonstrates the difficulties in diagnosing IgG4-associated diseases. Combination of ulcerative colitis and IgG4-associated pancreatitis described in this paper further complicates the differential diagnostic search, but at the same time, it does not exclude possible common pathogeneses of various autoimmune diseases in this group of patients.

Autoimmune pancreatitis versus pancreatic cancer

Autoimmune pancreatitis (AIP) is classified as a distinct form of pancreatitis according to the guidelines. It is characterized by imaging morphologic and histologic features and is associated with extrapancreatic manifestations in type1 IgG4-associated disease. Symptoms and findings almost always improve with administration of steroids. Differentiation from pancreatic ductal adenocarcinoma is required, particularly in the presence of AIP with focal parenchymal involvement. If AIP is suspected, abdominal ultrasound and/or endosonography, computed tomography (CT), and preferably magnetic resonance imaging (MRI) are indicated. A distinction is made between parenchymal and ductal changes that specifically indicate the presence of AIP. The diagnosis of autoimmune pancreatitis should be made based on the International Consensus Criteria (ICDC), in which the five main features (imaging, serology, histology, other organ involvement, response to steroid medication) are assessed. In type1 AIP, typical imaging changes are sufficient to establish the diagnosis even with negative histology, whereas for type2 AIP, histologic evidence is required. Imaging changes help in the differential diagnosis from pancreatic cancer. The following article addresses and evaluates crucial imaging diagnostic CT and MRI criteria for correct classification of findings, description of results, and differentiation of autoimmune pancreatitis from pancreatic cancer.

Idiopathic multicentric castleman’s disease mimicking immunoglobulin G4-related disease responding well to Bortezomib: a case report

BackgroundCastleman’s disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features.Case presentationThis case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient’s body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient’s clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable.ConclusionThe diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.

Salivary gland ultrasound or biopsy? : Comparison of methods based on case examples

Ultrasound examination of the salivary glands (SG) is aquick and noninvasive method to detect and semiquantitatively estimate typical changes in the large SG in Sjögren's syndrome (SS). The differential diagnosis of SS is difficult because several diseases and adverse effects of treatment have a similar clinical picture as SS with sicca syndrome and can even induce alterations in the SG (mimic diseases). Hence, for a long time an SG biopsy was regarded as the diagnostic procedure of choice, especially in SS‑A negative patients, whereas the significance of SD sonography is still controversially discussed. Comparison of typical and atypical changes for SS in the salivary glands in ultrasound and associated histological sections. This article describes six patient cases with antibody positive or negative SS with and without typical SS ultrasound patterns, SS-associated lymphoma, sarcoidosis and IgG4-associated disease. The findings of the sonographic examination of the parotid glands and the associated histology of the SD are explained and put into context. The SSA antibody positive patients with SS show atypical sonographic pattern with hypoechoic foci, especially if the disease has been present for along time. This pattern can help support the diagnosis of SS. The ultrasound patterns of the mimic diseases sometimes differ significantly from the typical patterns of pSS. The histological examination of the SG helps to corroborate the diagnosis but low histological focus scores, in particular, require acritical synopsis of the clinical, serological and imaging findings. Both salivary gland ultrasound and the histological examination of SG biopsies are justified in the diagnostics and differential diagnosis of SS and sicca syndrome.

Swelling of the salivary glands and sicca symptoms in Kimura's disease, arare rheumatological differential diagnosis with an indicatively high IgE serum level-Acurrent overview after literature search

Rheumatic and musculoskeletal diseases (RMD) include various diseases with sometimes rather different symptoms, some of which are locally confined and others show systemic features. Autoimmune phenomena, such as those occurring in Sjögren's syndrome, often cause symptoms such as xerostomia and xerophthalmia in association with inflammation of the salivary glands. The pathogenesis of these diseases is only partly clarified. This is similar to allergic diseases, which are otherwise clearly different with respect to the symptoms and pathomechanisms but swelling of the salivary glands can also rarely occur here. As this is apossible differential diagnosis of Sjögren's syndrome or also IgG4-associated diseases, and such acase was recently described, aliterature search was carried out in PubMed, the results of which are presented here and summarized in this article in abrief overview.

Gastroenterological manifestations of IgG4 associated disease. Literature review, clinical case

IgG4‑associated disease is a disorder with an unknown etiology and multi‑organ damage caused by a specific inflammatory process, characterized by periductal inflammatory infiltrate mainly by CD4+‑T lymphocytes, IgG4+‑plasma cells, storiform fibrosis, atrophy of acinar tissue, which often results in pancreatic duct stenosis. A great number of target organs are involved in the pathological process, one primary localization of the pathological process without damage to other organs is observed in only 10 — 20% of patients. Mostly affected are middle‑aged and elderly men. The pathological process is stipulated by a pronounced tissue infiltration with lymphocytes and plasma cells, followed by fibrosis development. The clinical picture varies widely, depending on the combination of affected target organs. The long‑term prognosis of the disease has not been sufficiently studied due to the small number of observations, the variety of clinical forms and the variability of treatment approaches. IgG4‑associated lesions have been described for localization in pancreas, biliary tract and gallbladder, liver, esophagus, stomach and intestines, retroperitoneal space, mammary glands and thyroid and prostate glands, salivary and lacrimal glands, kidneys and ureters, lymph nodes, skin and bones. The article presents a review of current literature on gastroenterological lesions in IgG4 associated diseases, as well as a clinical case of a patient with IgG4‑autoimmune pancreatitis type 1, IgG4‑sclerosing cholangitis, autoimmune hepatitis type 1 complicated by 3 type diabetes mellitus. The diagnosis of an IgG4‑associated disease in gastroenterological practice causes some difficulties. However, the timely diagnosis and administration of adequate treatment can significantly improve the quality of life of the patient and prevent the development of complications.

Features of the course of diabetes mellitus in IgG4-associated disease

IgG4-related disease (IgG4-RD) is characterized by the appearance of tumor-like foci in one or more organs, occurring synchronously or metachronously, due to fibro-inflammatory changes with hypersecretion of immunoglobulin G subclass 4 (IgG4) in tissues and/or blood serum. Diabetes mellitus (DM) develops among 43-68% of patients with IgG4-related pancreatitis. Diabetes against the background of IgG4-RD can be caused both by damage to the endocrine part of the pancreas and the use of glucocorticosteroids, but its course is moderate, with a rare need for insulin therapy. In both cases, the use of genetically engineered biological therapy with rituximab may be accompanied by an improvement in carbohydrate metabolism. This article describes the course of diabetes and the need for hypoglycemic therapy for 1.5 years in a patient treated with IgG4-RD.

The unique properties of IgG4 and its roles in health and disease.

IgG4 is the least abundant subclass of IgG in human serum and has unique functional features. IgG4 is largely unable to activate antibody-dependent immune effector responses and, furthermore, undergoes Fab (fragment antigen binding)-arm exchange, rendering it bispecific for antigen binding and functionally monovalent. These properties of IgG4 have a blocking effect, either on the immune response or on the target protein of IgG4. In this Review, we discuss the unique structural characteristics of IgG4 and how these contribute to its roles in health and disease. We highlight how, depending on the setting, IgG4 responses can be beneficial (for example, in responses to allergens or parasites) or detrimental (for example, in autoimmune diseases, in antitumour responses and in anti-biologic responses). The development of novel models for studying IgG4 (patho)physiology and understanding how IgG4 responses are regulated could offer insights into novel treatment strategies for these IgG4-associated disease settings.

The role of miRNA in the pathogenesis of diseases associated with functional dysregulation of the lacrimal gland

At this time, the mechanism causing lacrimal gland dysfunction is not understood completely. In diseases associated with lacrimal gland involvement (Sjogren's syndrome, sarcoidosis, IgG4-associated disease, etc.) patients have been observed to experience elevated cellular apoptosis, active production of autoantibodies to glandular tissue, increased level of pro-inflammatory cytokines, functional disruption of signaling molecules leading to changes in tear production. Difficulties in differential diagnosis of lacrimal gland dysfunction in above-listed diseases are associated, on the one hand, with similarity of the clinical picture of ophthalmological manifestations, and on the other hand - with complicated morphological interpretation of changes in the glandular tissues. In this view, miRNA is a promising diagnostic and prognostic marker that would help with differential diagnosis as well as with choosing the treatment tactics. Methods of molecular profiling and identification of "molecular phenotypes" of lacrimal gland and ocular surface damage will allow the use of miRNA as biomarkers and prognostic factors for personalized treatment.

Аутоиммунитет, аутовоспаление и почки

Systemic autoimmune and autoinflammatory disease are associated with all types of diffuse kidney disease, that is, glomerulonephritis (including rapidly progressive), thrombotic microangiopathy, tubulointerstitial nephritis, and AA-amyloidosis. However, the occurrence and types of nephropathies differ significantly in patients with various systemic immunemediated inflammatory diseases. For example, glomerulonephritis is one of the leading manifestation of systemic lupus erythematosus and small-vessels vasculitis, thrombotic angiopathy occurs frequently in patients with both primary and secondary antiphosholipid syndrome, tubulointerstitial nephritis is frequently found in patients with Sjogren syndrome and IgG4-associated disease, whereas AA-amyloidosis can complicate rheumatoid arthritis, ankylosing spondilytis, psoriatic arthritis, familial Meditarranean fever, and certain other monogenic autoinflammatory diseases. Over last decades, renal survival in patients with autoimmune and autoinflammatory diseases improved significantly due to earlier diagnosis and development of effective immunosuppressive and anti-inflammatory treatments. However, a proportion of patients still present with progressive impairment of kidney function that can be unrelated to activity of underlying diseases.

Zriedkavá príčina nebolestivého obštrukčného ikteru u starších ľudí – séria kazuistík

Summary: A series of two case reports discusses the differential diagnosis of painless jaundice in the elderly and points to autoimmune pancreatitis as one of its rarer causes. In search for the cause, the first step is to rule out the malignant origin of the obstruction using the clinical picture, imaging examinations, and EUS-guided biopsy. An imaging examination can initially point to the possibility of autoimmune pancreatitis, but in the case of focal pancreatic involvement the distinction from cancer is unreliable. Elevated concentration of IgG4 antibodies can further increase the probability of IgG4-associated pancreatitis. Histological examination of the pancreas will help reveal typical features of autoimmune pancreatitis such as lymphoplasmacytic infiltrate, storiform fibrosis, obliterating phlebitis and increased number of IgG4 positive plasma cells. Once the diagnosis is probable, it is advisable to start a treatment with steroids. A quick decrease in cholestatic markers and bilirubin is typical. Patients with autoimmune pancreatitis require long-term follow-up, to adjust the treatment in case of relapses, the risk of developing exocrine or endocrine insufficiency, and in case of IgG4 associated disease due to the risk of other organ systems involvement. The risk of pancreatic cancer is still a matter of discussion. Key words: autoimmune pancreatitis – IgG4 – obstructive jaundice – case report

Systemic manifestations of IgG4-associated disease

The article presents general data on IgG4-associated disease, as well as its classification and universal diagnostic criteria. Attention is focused on the possibility of multi-organ lesions, which complicates diagnosis and treatment. A clinical case of an IgG4-associated disease involving the retroperitoneal space (retroperitoneal fibrosis), lungs (bilateral interstitial pneumonia, diffuse and focal fibroid lung), intestines (chronic colitis) in a middle-aged man is described. Sequential administration of glucocorticoids and monoclonal antibodies made it possible to bring a patient into remission, however, the recurrence of the disease required the resumption of hormone therapy at a reduced dose with a positive effect.

IgG4-related disease with nasopharyngeal malignancy-like manifestations

Objective:The purpose of this article was to discuss the clinical features and imaging characteristics of IgG4-related disease（IgG4-RD） in order to identify nasopharyngeal IgG4-RD at an early stage. Methods:The basic information of the patients, including age, sex, symptoms, disease duration and treatment process, was collected through the electronic case system. Laboratory tests including nasal endoscopy, EBV levels, IgG4 levels and C-reactive protein levels were recorded during hospitalization and outpatient follow-up. All radiological imaging and postoperative pathology data are collected, analyzed and summarized. Results:All patients underwent partial excisional biopsy of the lesion. The pathological findings showed inflammatory granulomatous and fibrous tissue hyperplasia with a high infiltration of lymphocytes, plasma cells and neutrophils, and immunohistochemistry examination showed IgG4+ plasma cells were more than 10 per high magnification field. Combining medical history, imaging, serological findings and relevant treatment, all four patients were diagnosed with IgG4-associated disease. And their symptoms improved significantly after hormonal and immunosuppressive treatment. Conclusion: IgG4-RD has a highly similar clinical presentation with nasopharyngeal carcinoma. Differentiation from IgG4-RD should be considered for those pathology cannot be clarified by multiple biopsies. Timely diagnosis of IgG4-RD is important to prevent secondary organ damage in patients with active disease.

IgG4 immunoglobulin subclass and related pathological conditions or how to effectively imitate cancer disease.

IgG4 is the least represented subclass of human imunnoglobulines G (IgG) in serum and differs from other antibodies by its unique bio-logical properties. Although its function in the immune response is not entirely clear, it is mainly involved in the regulation of the immune response. It is formed as a result of chronic or strong antigenic stimulation; in such a case, it becomes a predominantly formed IgG subclass. IgG4 play a key role in the immune tolerance in allergies and tumors. The tolerogenic potential of IgG4 is used in the treatment of allergic diseases using the allergen immunotherapy; at the same time, it is also involved in inducing the immunological tolerance in the microenvironment of tumors, which promotes tumor progression. The increase of serum IgG4 is associated with relatively recently described groups of diseases. In addition to the IgG4-autoimmune diseases, it is mainly connected with IgG4-associated diseases (IgG4-RD) where various organs of the human body are affected by the formation of fibrous and sclerosing deposits in this group of the immune-mediated diseases, which leads to specific organ dysfunction. The most commonly affected organs include the pancreas and large salivary glands; moreover, the orbits and lacrimal glands, the biliary tract, the lungs, the kidneys, the retroperitoneum, the aorta, the meninges, and the thyroid gland may also be affected. It is not entirely clear whether these patients have a higher prevalence of cancer than the general population; however, there is also another relationship between IgG4 and cancer. IgG4-RD very often imitate advanced cancer in medical imaging techniques, so its existence should also be considered in the differential dia-gnosis of malignancies. The aim of this article is to draw attention of clinical oncologists to the issue of IgG4-associated diseases group which can mimic cancer condition in various organs in the human body. Therefore, it is necessary to bear them in mind in the differential dia-gnosis of malignant diseases.