The Omenn's syndrome: Histological, immunohistochemical and ultrastructural evidence for a partial T cell deficiency evolving in an abnormal proliferation of T lymphocytes and S-100+/T-6+ Langerhans-like cells

Abstract

A 7 month old female infant was affected by a rapidly fatal familial disease highly reminiscent of Omenn's syndrome. She presented with widespread eczematous lesions, hepatosplenomegaly, superficial lymphadenopathy, peripheral blood lymphocytosis, eosinophilia and hyper-IgE. An axillary lymph node was involved by a marked proliferation of T-3 +/T-10-- lymphocytes admixed with S-100+/T-6+/Leu-3a+/Ia + reticular cells which lacked typical LC granules; cell suspension study revealed that 90%-96% of the lymph node cells were T-11+/T-3+ lymphocytes characterized by low expression of Leu-3a and T-8 antigens and by high expression of Ia antigens (52%). Peripheral blood T lymphocytes exhibited a similar distribution of surface phenotypes. The patient died of interstitial pneumonia and an autopsy was performed. The thymus was markedly atrophic and completely devoid of lymphocytes. The peri-arteriolar lymphoid sheets of the spleen were poorly developed and were mainly composed of T-8+ lymphocytes. The mediastinal nodes were rudimentary and were populated by T-3+/T-10+ lymphocytes with low expression of Leu-3a and T-8 antigens. Our results raise the possibility that Omenn's syndrome is a peculiar primary immunodeficiency in which, despite early thymic involution, some abnormal T lymphocytes still develop in the peripheral lymphoid organs. Antigenic triggering of these cells might result in prominent proliferations of T lymphocytes and Langerhans-like cells which lead to the clinical manifestation of the disease.

Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome).

“…Omenn's syndrome is a genetic disorder with recessive autosomal inheritance (1)(2)(3)(4)(5)(6)(7)(8)(9), characterized by lymphocytic infiltration ofthe skin, gut, liver, and spleen, leading to erythroderma and protracted diarrhea with failure to thrive. Blood T lymphocyte and eosinophil numbers are high, but there is marked lymphocyte depletion in the thymus and lymphoid tissues (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

“…Blood T lymphocyte and eosinophil numbers are high, but there is marked lymphocyte depletion in the thymus and lymphoid tissues (1)(2)(3)(4)(5)(6)(7)(8)(9). The syndrome is clearly due to an intrinsic defect of the lymphocyte lineage since it is curable by bone marrow transplantation (22).…”

“…Omenn's syndrome or combined immunodeficiency with hypereosinophilia is characterized by the early occurrence of diffuse erythroderma, hepatosplenomegaly, protracted diarrhea, and failure to thrive (1)(2)(3)(4)(5)(6)(7)(8). A large number ofpoorly functional T cells and eosinophils are present in the blood and infiltrate the skin, gut, liver, and spleen (5)(6)(7)(8).…”

“…A large number ofpoorly functional T cells and eosinophils are present in the blood and infiltrate the skin, gut, liver, and spleen (5)(6)(7)(8). In contrast, the lymph nodes and thymus are profoundly depleted of lymphocytes.…”

“…In contrast, the lymph nodes and thymus are profoundly depleted of lymphocytes. As the lesions are very similar to those observed in graft-versus-host disease (GVHD)' (5)(6)(7)(8) it has been proposed that GVHD is causal, but this has not been substantiated by the detection of foreign T lymphocytes (5)(6)(7)(8)(9). The autosomal recessive inherited nature of the syndrome strongly suggests that it is a primary immunodeficiency (1).…”