The role of IgG4-positive plasma cell population in classic Hodgkin lymphoma

Abstract

The effect of IgG4, which constitutes the least of the IgG subclasses, on the pathogenesis and prognosis of lymphoma or solid tumors is one of the research topics of interest in recent years. The role of IgG4, which has been reported to suppress antitumor immunity, in classic Hodgkin's lymphoma (cHL), which is recognized by its pathognomonic microenvironment, is not yet clearly known. The aim of this study was to determine IgG4-positive plasma cell density in the cHL microenvironment and to compare it with histopathological and clinical parameters. In addition, the role of the increase in IgG4-positive cells in the development of relapse after treatment was also investigated. A retrospective cross-sectional study. Ninety-four patients with the initial diagnosis of cHL who had no comorbidity or no treatment history and forty-one reactive lymph nodes with follicular hyperplasia findings were included in the study. Three hot-spot areas were identified with reference to the IgG4 sections. Mean IgG4-positive plasmacyte counts and IgG4/IgG ratios were determined and compared with histopathological characteristics. The mean IgG4 + plasma cell count was 33.57 in cHL cases and 47.04 in the control group (p = 0.233). IgG4/IgG ratio was significantly higher in cHL compared with the control group (0.27 vs. 0.21, p = 0.021). The IgG4/IgG ratio was found to be higher in younger patients with classic Hodgkin lymphoma, with a low correlation (p = 0.028, r = - 0.226). There was no relationship with gender, lymph node location, histological subtype, EBV positivity and bone marrow infiltration. It was observed that IgG4/IgG ratio was higher in early-stage patients (p = 0.022). No significant IgG4 + cell increase was detected in the initial diagnosis and relapse slides of six patients who developed relapse after standard treatment, resulting in a cure. Novel therapeutic modalities targeting microenvironmental components have been reported to show dramatic effects, particularly in relapsed or refractory patients. Detailed characterization of the cHL inflammatory milieu will be useful for the identification of alternative targets. IgG4 subclass antibodies, which have been described to have anti-inflammatory effects, may have prognostic significance in a proportion of cHL patients.

Keywords: Hodgkin lymphoma; IgG4; IgG4/IgG ratio; Tumor microenvironment.