The diagnostic criteria for IgG4-related MD are (i) Symmetrical swelling of at least two pairs of lachrymal, parotid, or submandibular glands for at least 3 months and (ii) Elevated serum IgG4 (>135 mg/dL) or (iii) Histopathological features including lymphocyte and IgG4+ plasma cell infiltration (IgG4+ plasma cells/IgG+ plasma cells >50%) with typical tissue fibrosis or sclerosis . This case fulfilled all three diagnostic criteria and thus a diagnosis of IgG4-related MD was made. The permeation of IgG4-positive cells was seen in the paranasal sinus mucosa of this case and thus the patient also had a diagnosis of IgG4-related CRS. These IgG4-positive cells in the paranasal lamina propria exhibited morphology similar to that of the plasma cells that produce IgG4 in the paranasal mucosa, as previously reported [1-4]. Furthermore, some epithelial cells were stained by anti-IgG4 antibodies, suggesting the presence of some antigens specific for IgG4. Accordingly, we speculated that the IgG4 antibody synthesized by plasma cells was deposited in the epithelium in response to these antigens.
The IgE-positive cells found in the paranasal lamina propria exhibited morphology similar to that of mast cells. These IgE-positive cells may be related to eosinophil permeation in the paranasal sinus mucosa.
To analyze the nature of IgG4 and IgE production in our patient, we identified antigen-specific IgG4 and IgE antibodies in the serum and determined their levels, although the values were all extremely low despite high total serum IgG4 and IgE levels. Therefore, we speculate that the IgG4 and IgE antibodies detected in the serum from this case were nonspecific or specific for an unknown antigen.
We thought that the lesion with submandibular gland and the paranasal sinus mucosa was almost the same, because the pathology image resembles each other, for example. A large number of fibrosis tissues and the inflammatory cells appearing in both lesions.
In the present study, we used the PEG technique to assess serum immune complexes in this case. The patient’s serum levels of IgG4 and IgE were higher than the normal values and his serum levels of IgG4-IC and IgE-IC were likewise higher than those of two control individuals. His IgE PP index was also high (normal PP index <20%). Thus, large amounts of IgG4-IC and IgE-IC are present in this patient’s serum, which is not observed under general allergy or asthmatic conditions.
We hypothesize that the IgG4 and IgE in the patient’s serum were autoantibodies for a component of the paranasal sinus mucosa and submandibular gland tissue because (i) Some epithelial cells of the paranasal mucosa were stained by anti-IgG4 antibodies (ii) The levels of antigen-specific IgG4 and IgE antibodies in his serum were all extremely low despite high total serum IgG4 and IgE levels and (iii) Large amounts of IgG4-IC and IgE-IC exist the patient’s serum. We therefore believe that these autoantibodies caused chronic inflammation of the paranasal sinus and submandibular gland in this case.
The IgE autoantibody may cause the protracted type I allergy. It is thought that the IgG4 autoantibody causes intractable inflammation, but the details are unclear.
We previously reported a case of female Eosinophilic Granulomatosis with Polyangitis (EGPA) where we used PEG precipitation to evaluate the patient’s levels of IgE-IC, and we speculated that circulating IgE-IC was formed by anti-neutrophil IgE autoantibodies . We herein report a case of male IgG4-related MD with CRS with high serum levels of IgG4-IC and IgE-IC. We propose that the IgG4 and IgE in his serum were autoantibodies for a component of the paranasal sinus mucosa and submandibular gland tissue.