Cytokine profiles contribute to understanding the pathogenic difference between Good syndrome and oral lichen planus: two case reports and literature review

Abstract

We described and analyzed the pathogenic difference between Good syndrome (GS) and oral lichen planus (OLP) in oral mucosa. Good syndrome (GS) is a rare disease characterized by B and T cell immunodeficiency associated with hypogammaglobulinemia and thymoma. GS patients frequently develop oral lichenoid lesions with lymphocytic infiltration beneath the basal layer. Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa characterized by destruction of basal cells by Langerhans cells, macrophages, and T lymphocytes. Although the histological features of the lesions of both diseases are very similar, the pathogenesis of GS in the oral mucosa remains unknown. In this study, we thus investigated the expression of infiltrating lymphocyte subsets (CD3, CD20, CD4, and CD8) and T helper (Th) cytokines including interferon (IFN)-γ (Th1 type), interleukin (IL)-4 (Th2 type), IL-17 (Th17 type), and IL-10 (regulatory T cell type) by immunohistochemistry in buccal mucosa specimens from 2 GS patients compared with 15 OLP patients. All patients showed a predominance of CD3 T cells over CD20 B cells, and CD4 Th cells over CD8 cytotoxic T cells. This polarization was especially prominent in GS. IFN-γ and IL-10 were strongly detected in the infiltrating lymphocytes of all patients. However, IL-4 and IL-17 were detected in OLP patients only. These results suggest that the pathogenesis of GS is different from that of OLP. GS is a unique inflammatory disorder characterized by dysfunction of Th2 and Th17 immune reactions via abnormal T-B cell interaction.

FIGURE 1

Clinical findings in oral cavity from patient with Good syndrome (GC) (Case 1). (A) Oral mucosa and tongue at the initial visit. (B) Oral mucosa and tongue after thymectomy.

FIGURE 2

Imaging and histological findings in thymus gland from patient with Good syndrome (GS) (Case 1). (A) Computed tomography findings demonstrating mediastinal abnormality and mass in the anterior mediastinum (yellow circle). (B) Thymus gland specimen was stained with hematoxylin and eosin (HE). Scale bar, 50 μm.

FIGURE 3

Lymphocyte subsets in the buccal mucosa from patients with GS and OLP. (A) Buccal mucosa specimens from representative patients with GS and OLP were stained with HE (a and j) and anti-CD3 (b, c, k, and l), anti-CD20 (d, e, m, and n), anti-CD4 (f, g, o, and p), and anti-CD8 (h, i, q, and r) monoclonal antibodies. Counterstaining with Mayer hematoxylin was subsequently performed. Scale bars, 100 μm. (B) Number of CD3, CD20, CD4, and CD8⁺ cells per HPF were counted in 1-mm² sections from 5 different areas from patients with GS (n = 2) and OLP (n = 15). GS = Good syndrome, HPF = high-power field, OLP = oral lichen planus.

FIGURE 4

Distribution of T helper cytokines in the buccal mucosa from patients with GS and OLP. Immunostaining with anti-IFN-γ (a, b, i, and j), anti-IL-4 (c, d, k, and l), anti-IL-10 (e, f, m, and n), and anti-IL-17 (g, h, o, and p) monoclonal antibodies in buccal mucosa of representative patients with GS and OLP. Counterstaining with Mayer's hematoxylin (blue). Scale bars, 100 μm. (B) Number of IFN-γ, IL-4, IL-10, and IL17⁺ cells per HPF were counted in 1-mm² sections from five different areas from patients with GS (n = 2) and OLP (n = 15). GS = Good syndrome, HPF = high-power field, IFN = interferon, IL = interleukin, OLP = oral lichen planus.