scholarly journals CXCL12/SDF-1 in IgG4-Related Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Riccardo Capecchi ◽  
Cristina Croia ◽  
Ilaria Puxeddu ◽  
Federico Pratesi ◽  
Andrea Cacciato ◽  
...  
Keyword(s):  
B Cell ◽  
Autoimmune Pancreatitis ◽  
Cancer Metastasis ◽  
Pathological Condition ◽  
White Blood Cells ◽  
Ductal Adenocarcinoma ◽  
Cxcl12 Expression ◽  
Hematopoietic Stem ◽  
Related Disease ◽  
Igg4 Related Disease

Background: SDF-1/CXCL12 is a chemokine with pleiotropic functions in hematopoietic stem cell niche homeostasis, germinal center architecture, B cell maturation, neoangiogenesis, and fibrosis. Recently, the CXCL12/CXCR4/CXCR7 axis was associated with cancer metastasis and autoimmune diseases. The IgG4-related disease (IgG4-RD) is a pathological condition characterized by IgG4+ plasma cells infiltrating fibrotic lesions. The aim of this research is to investigate the relevance of SDF-1/CXCL12 in IgG4-RD.Materials and Methods: Peripheral blood samples were collected before therapy from a single-center cohort of 28 IgG4-RD patients, fulfilling the ACR-EULAR classification criteria. Clinical and serological data were obtained for each patient. In total, 14 healthy donors (NHS), 9 patients with pancreatic ductal adenocarcinoma (PDAC), and 9 with Sjogren syndrome (SSj) were recruited as controls and screened for circulating SDF-1/CXCL12 by ELISA. Moreover, paraffin-embedded pancreatic biopsies obtained from patients with IgG4-RD (n = 7), non-autoimmune pancreatitis (n = 3), PDAC (n = 5), and control tissues (n = 4) were analyzed to study the tissue expression and localization of SDF-1/CXCL12 and one of its receptors, CXCR4, and their potential relation with neutrophil extracellular traps (NETs).Results: IgG4-RD patients had higher serum levels of SDF-1/CXCL12 than normal controls (p = 0.0137). Cytokine levels did not differ between the IgG4-RD autoimmune pancreatitis (AIP) and retroperitoneal fibrosis nor between the single- and multiple-organ involvement. No correlation was seen with the IgG4-RD Responder Index, IgG4 levels, white blood cells, or inflammatory markers in the serum. When compared to SSj, the IgG4-RD AIP subgroup presents higher amounts of serum SDF-1/CXCL12 (p = 0.0275), while no differences are seen in comparison with PDAC. The expression of SDF-1/CXCL12 in the tissue was significantly higher in the IgG4-RD tissue than the normal pancreas, and the tissue with the high SDF-1/CXCL12 expression is characterized by the overall inflammatory cell infiltration, fibrosis, and high level of NETs.Conclusion: Modulating B cell development, neoangiogenesis and fibrosis, and SDF-1/CXCL12 may play a role in IgG4-RD. The higher levels observed in IgG4-RD, as compared to SSj, which closely mimics the disease, can be related to a different pattern of lesions, with prevalent fibrosis seen in IgG4-RD. Taken together, these findings suggest that drugs acting on the CXCL12/CXCR4/CXCR7 axis may affect IgG4-RD.

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

2011 ◽  
Vol 46 (3) ◽  
pp. 277-288 ◽  
Author(s):  
Kazuichi Okazaki ◽  
Kazushige Uchida ◽  
Masanori Koyabu ◽  
Hideaki Miyoshi ◽  
Makoto Takaoka
Keyword(s):  
Autoimmune Pancreatitis ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Recent Advances

Immunoglobulin G4, Autoimmune Pancreatitis and Pancreatic Cancer

2014 ◽  
Vol 33 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Martina Bojková ◽  
Petr Dítě ◽  
Jana Dvořáčková ◽  
Ivo Novotný ◽  
Katarina Floreánová ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Steroid Therapy ◽  
Autoimmune Pancreatitis ◽  
Normal Limit ◽  
Serum Levels ◽  
Pancreatic Tissue ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Igg4 Level

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy.

Sign in / Sign up

Export Citation Format

Share Document