Recent advances in understanding and managing IgG4-related disease

Wolfson, Anna R.; Hamilos, Daniel L.

doi:10.12688/f1000research.9399.1

Cited by 19 publications

(22 citation statements)

References 76 publications

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“…Our results are in line with studies on IgG4‐related disease (IgG4‐RD), a fibro‐inflammatory condition characterized by abundant IgG4 + plasma cells in affected tissues, and by specific involvement of Th2, Treg cells, and M2 macrophages . A Japanese genomewide association study of IgG4‐RD reported three susceptibility loci consistent with an antigen‐driven disease.…”

Section: Discussionsupporting

confidence: 90%

IgG4 drives M2a macrophages to a regulatory M2b‐like phenotype: potential implication in immune tolerance

Bianchini

Roth‐Walter

Ohradanova‐Repic

et al. 2018

Allergy

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Background Macrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes ( IC s), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known. Objective We aimed to refine the original method by applying precisely defined IC s of the subclasses IgG4 or IgG1 constructed by two independent methods. Methods Monocyte‐derived macrophages ( MDM s) were treated with M‐ CSF , followed by IL ‐4/ IL ‐13 to induce the M2a allergic phenotype. To mimic unspecific or allergen‐specific IC s, plates were coated with myeloma IgG1 or IgG4, or with grass pollen allergen Phl p 5 followed by recombinant human Phl p 5‐specific IgG1 or IgG4. M2a polarized macrophages were then added, cultured, and examined for cellular markers and cytokines by flow cytometry, ELISA , and rt PCR . Alternatively, immune complexes with IgG1 or IgG4 were formed using protein L. Results IgG4 IC s down regulated CD 163 and CD 206 on M2a cells, and significantly increased IL ‐10, IL ‐6, TNF α, and CCL 1 secretion, indicating a shift to an M2b‐like phenotype. Treatment with IgG4 IC s resulted in expression of Fcγ RII and down modulation of Fcγ RII compared with IgG1 treated cells ( P = 0.0335) or untreated cells ( P < 0.00001). Conclusion Immune complexes with subclasses IgG1 and IgG4 can in vitro be generated by plate absorption, and in fluid form by protein L. Cross‐linking of Fcγ RII b by the IgG4 subclass redirects pro‐allergic M2a macrophages to an M2b‐like immunosuppressive phenotype. This suggests an interplay of macrophages with IgG4 in immune tolerance, likely relevant in allergen immunotherapy.

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Section: Discussionsupporting

confidence: 90%

IgG4 drives M2a macrophages to a regulatory M2b‐like phenotype: potential implication in immune tolerance

Bianchini

Roth‐Walter

Ohradanova‐Repic

et al. 2018

Allergy

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“…In our group of 52 patients, we found 7 patients fulfilling the criteria for IgG4-ROD diagnosis. Among these patients, there was a noticeable predominance of males, which is in agreement with the previous data [19,30,31]. Additional characteristics, such as obesity, advanced age, and high BMI and ABSI, suggesting high risk of sarcopenic obesity,were also consistent with current literature [1,17,19,30,32].…”

Section: Discussionsupporting

confidence: 92%

“…As we often find elevated IgG in allergic patients, it is necessary to monitor a wide range of possible clinical manifestations, which can be connected with high IgG4 levels [19]. We based our evaluation on the frequency of their occurrence, which was established by Wolfson and Hamilos [31]. During our study, we found no additional clinical impairments which would request the need of targeted therapy.…”

Section: Discussionmentioning

confidence: 77%

“…The same is true of signalization of inflammatory reaction by activation of inflammatory proteins, which can be related only to obesity of tested individuals [13,26]. We consider clinical manifestation of IgG4-RD to be the deciding marker [14,15,19,31]. An important criterion necessary for optimal assessment of IgG4-RD diagnosis is evaluation of IgG4 levels.…”

Section: Discussionmentioning

confidence: 99%

“…IgG4 levels higher than 2.01 mg/ml suggest specificity to be 89% and lower (80%) sensitivity [33]. Criteria for IgG4-RD are changing and different authors use limits from 1.35 mg/ml to 2.48 mg/ml [7,14,15,[17][18][19][20]31,33]. Many authors now agree that the IgG4/IgG ratio is a better marker and levels above 10% are usually considered to be significant [14,[16][17][18]22].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

IgG4-Related orbital disease in patients with diabetic retinopathy: Effects of glucan and vitamin D supplementation

Richter¹,

Zahradnicka²,

Větvička³

et al. 2018

Pathol Discov

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Background: Diabetic retinopathy represents a serious complication of diabetes. Methods: In our group of 52 patients, we identified 7 individuals (13%) with elevated levels of IgG4. Results: Detailed examination revealed significant clinical changes, resulting in a diagnosis of probable IgG4-RD. Conclusions: Long-term evaluation and beta glucan supplementation, combined with vitamin D supplementation, during general treatment of these patients significantly improved both health and mental conditions.

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Immunoglobulin G4‐related disease mimicking gallbladder cancer with associated choledochal cyst: A case report of a malignant masquerade

et al. 2019

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Immunoglobulin G4 (IgG4)‐related disease is a recently described autoimmune disease that can involve diverse organ systems, causing pancreatitis, cholangitis, retroperitoneal fibrosis, and thyroiditis to name a few. Key histological features include storiform fibrosis, obliterative venulitis, and intense inflammatory infiltrate composed of lymphoplasmacytic cells. The disease has a tendency to present with mass‐forming lesions, often difficult to differentiate from malignant processes. We report the case of a 48‐year‐old male from an area endemic for gallbladder cancer (north India). He presented with a short history of abdominal pain and was found to have asymmetric thickening of the gallbladder wall with a soft‐tissue mass invading the adjacent liver. In addition, the bile duct was dilated throughout its extent. A clinical and radiological diagnosis of gallbladder cancer with choledochal cyst was made, and the patient underwent radical cholecystectomy with bile duct excision. Histopathology surprisingly demonstrated IgG4‐related disease with no evidence of malignancy. Notably, serum levels of immunoglobulins were found to be normal. Preoperative diagnosis was challenging due to the absence of other manifestations. IgG4‐related disease is a possible diagnostic pitfall and should be included as a possible differential diagnosis for gallbladder masses.

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Recent advances in understanding and managing IgG4-related disease

Cited by 19 publications

References 76 publications

IgG4 drives M2a macrophages to a regulatory M2b‐like phenotype: potential implication in immune tolerance

IgG4 drives M2a macrophages to a regulatory M2b‐like phenotype: potential implication in immune tolerance

IgG4-Related orbital disease in patients with diabetic retinopathy: Effects of glucan and vitamin D supplementation

Immunoglobulin G4‐related disease mimicking gallbladder cancer with associated choledochal cyst: A case report of a malignant masquerade

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