Immunopathology of ocular sarcoidosis

Abstract

Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.

Ocular sarcoidosis: clinical experience and recent pathogenetic and therapeutic advancements

“…Although the etiology of sarcoidosis is unknown, a better understanding of the pathogenetic mechanisms underlying its onset is clearly important for the development of a more rational and effective therapeutic approach. The basic mechanism that triggers and maintains the inflammatory state is an interaction between lymphocytes and macrophages within the granulomatous areas, with the compartmentalization of T-cells expressing the helper (Th) phenotype [43]. Immunologically, sarcoidosis is characterized by an exaggerated Th type 1 (Th1) immune response to a so far unknown antigen(s) (Fig.…”

Immunology of Extrapulmonary Sarcoid Lesions

“…We have therefore taken advantage of a large panel of MAbs and histochemical techniques to document the development of sarcoid granuloma within the conjunctival mucosa. 56 The following parameters have been taken into account: presence of macrophages stained for nonspecific esterase (alpha-naphthyl acetate esterase [ANAE]), and morphologic characterization of the surrounding inflammatory cells; presence of lymphocytes stained with MAbs specific T or B markers; and presence of lymphoid follicles, detected by MAbs specific for follicular dendritic cells and B lymphocytes.…”

“…In both cases a preponderant amount of lymphocytes characterized by the helper-related phenotype (Leu3+, not shown) surrounds the macrophagic aggregates. (Reproduced with permission from Angi et al56 )…”