Is sarcoidosis an autoimmune disease?: Report of four cases and review of the literature

Abstract

Summary Four cases of sarcoidosis coexisting with connective tissue diseases are described: three cases of sarcoidosis coexisting with PSS, and one case of sarcoidosis coexisting with SLE. Reports of sarcoidosis combined with uncommon connective tissue diseases have been rare in the literature. The topic immunoregulation is briefly reviewed. A complexed system of both positive and negative regulatory factors are responsible for generating and maintaining an optimum immune response. The cell types that participate in modulating this system are T lymphocytes, B lymphocytes, and macrophages. Recent work has shown that these major groups of cells can be further divided into functional subclasses such as the helper T-cell and the suppressor T-cell. Interaction between these cell types and the other cellular constituents of the immune response is carried out by means of humoral factors and direct cell-to-cell contact. Deranged immunoregulation has been shown to play a major role in the pathogenesis of several disease states, including the autoimmune disease of New Zealand mice, human SLE, agammaglobulinemia, and the immuno-deficiencies of multiple myeloma, Hodgkin disease, and disseminated fungal infections. The role of defective immunoregulation in the animal model, New Zealand mice, is reviewed. The pathogenesis of this disease is most likely due to defective suppressor T-cell function. Augmenting suppressor function, by administering a humoral suppressor factor, has resulted in the disappearance of the manifestations of the disease. Evidence in support of the contention that sarcoidosis shares a similar defect of suppressor cell function with New Zealand mice, SLE, and possibly PSS is presented and includes: (1) A marked similarity in the features and abnormalities of the immune system between these diseases such as (A) A hyperactivity of the humoral immune system; (B) A defect in several parameters of cell-mediated immune function; (C) A loss of tolerance to self-antigens with the appearance of auto-antibodies and the development of the manifestations of cell-mediated hypersensitivity. Antilymphocyte antibodies, most likely directed towards T-cells, can also be demonstrated in SLE and sarcoidosis; (D) a depression of antibody dependent cell-mediated cytotoxicity in SLE and sarcoidosis. An increase in null cells in both diseases can also be shown; and (E) Similar alterations of circulating monocytes most likely representing activation of these cells. Possibilities for the etiology and pathogenesis of the deranged immunoregulation proposed for these diseases are discussed. A complicated interplay of both genetic and viral factors are likely to be involved in the causation of New Zealand mice disease, SLE, and sarcoidosis that are ultimately expressed through alteration of the intricate immunoregulatory system. The immunologic features and abnormalities of these disease states are a manifestation of this defect. The potential therapeutic implications of these findings are discussed. The ability to manipulate various aspects of the immunoregulatory system, such as augmenting suppressor function, may be applicable to both SLE and sarcoidosis and could be prerequisite for ultimate therapeutic intervention.