IgG4‐Related Disease: Clinical and Laboratory Features in One Hundred Twenty‐Five Patients

Abstract

Purpose IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. No detailed clinical and laboratory assessments have been reported in large numbers of patients with IgG4-RD diagnoses established by strict clinicopathological correlation. Methods We reviewed the baseline features of 125 patients with biopsy-proven disease. The diagnosis was confirmed by pathology review according to consensus diagnostic criteria. Disease activity and damage were assessed by the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts. Results Of the 125 patients, 103 had active disease and 86 were on no treatment. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher RI, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 (P<0.01 for all comparisons). The correlation between IgG4+ plasmablast level and RI (R=0.45, P=0.003) was stronger than that of total plasmablasts and RI. Seventy-six (61%) of the patients were male, but no significant differences according to gender were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Glucocorticoids failed to produce sustained remission in the majority of patients. Conclusion Nearly 50% of this patient cohort with biopsy-proven, clinically-active IgG4-RD had normal serum IgG4 concentrations. Serum IgG4 elevation identify a subset with more inflammatory features. IgG4+ plasmablasts correlate well with disease activity.

Case Follow-Up: Development of Primary Membranous Glomerulonephritis in a Patient with IgG4 Related Disease

“…As physicians become more aware of the diagnosis of IgG4-RD and more data from IgG4-RD patients is gathered, classification criteria may continue to evolve to become more accurate. With this in mind, we acknowledge that our patient did not meet strict comprehensive diagnostic criteria for IgG4-RD, as the ratio of IgG4+/IgG cells was 30%, not greater than 40% [10]. At the time of the pathology report, storiform fibrosis and obliterative phlebitis were not known characteristic features of IgG4-RD and thus not commented on, but the pathologist did feel that the 'Castleman disease-like, follicular hyperplasia and interfollicular expansion by immunoblasts and plasma cells' was compatible with IgG4-RD due to literature available at the time [11].…”

“…The patient was started on an angiotensin converting enzyme inhibitor (ACEi) and as needed diuretics with resolution of her lower extremity edema However, there are speculations about potential improvements in the criteria. These include the concern that normal serum IgG4 levels are present in roughly 50% of patients with IgG4-RD, and that IgG4 plasmablasts may be a more accurate representation of disease activity [10]. As physicians become more aware of the diagnosis of IgG4-RD and more data from IgG4-RD patients is gathered, classification criteria may continue to evolve to become more accurate.…”

Immunoglobulin G4-Related Disease, Presented with Retroperitoneal Fibrosis and Monoclonal Gammopathy: Case Report and Mini Review

“…Taking into consideration that elevated serum levels of IgG4 are observed only in 60-70% of patients with IgG4-RD and not necessarily needed to confirm the diagnosis [7,41,42], normal level of IgG4 don't rule out this diagnosis. We believe that RPF in this particular case is the solely one manifestation of IgG4-RD, as we did not find any data in favor of aortic aneurism, pericarditis, Riedel's thyroiditis and pancreatitis or any other typical for IgG-RD organ involvement.…”

“…Main changes, characteristic for IgG4-RD are tumor-like swelling of involved organs, lymphoplasmacytic tissue infiltration with the predominance of IgG4 positive plasma cells and CD4 positive T lymphocytes, modest tissue eosinophilia, and so-called "storiform" fibrosis with cartwheel appearance of the arranged fibroblasts and inflammatory cells; 60-70% of patients demonstrate also elevated IgG4 serum concentrations [1][2][3][4][5][6][7][8][9]. IgG4-RD is regarded as a fibroinflammatory condition, which pathogenesis is not fully understood, and the pathogenic role of IgG4 is still under discussion.…”

Intrathoracic Manifestations of IgG4-Related Disease

“…1 The common organs involved in IgG4-RD include the submandibular glands, lymph nodes, orbits, and pancreas. 2 However, this disease process has been reported to affect almost every organ system. Intrathoracic involvement in IgG4-RD, the subject of this review, may occur commonly but is frequently overlooked.…”