Nonviable Autologous Bronchoalveolar Lavage Cell Preparations Induce Intradermal Epithelioid Cell Granulomas in Sarcoidosis Patients

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Abstract
Intracutaneous injection of sarcoidosis patients with Kveim-Siltzbach antigen (KSAg), a particulate suspension of granulomatous sarcoidal spleen, induces an influx of T-helper lymphocytes and monocyte-macrophages followed by epithelioid cell granuloma formation. In the lung, similar granulomas form from an alveolitis of similar mononuclear cells, which may harbor a Kveim-like granulomagenic factor. To assess this possibility, preparations of nonviable autologous bronchoalveolar lavage cells (NABC) and KSAg were injected intracutaneously at different sites and biopsied at 4 to 5 wk. Of 22 sarcoidosis patients, nine (41%) developed typical granulomas at the NABC site, while all developed granulomas at the KSAg site. Responders to NABC had more recent onset of symptoms than nonresponders (3.2 versus 23.7 months, p less than 0.01), but did not have significantly higher percentages of lavage lymphocytes or more rosetting of lymphocytes about alveolar macrophages. None of 11 normal volunteers developed granulomas in response to NABC. Epithelioid cell granulomas at NABC and KSAg sites were similar by hematoxylin-eosin staining and by biotin-avidin-peroxidase immunohistochemical staining with monoclonal antibodies Leu-1, Leu-14, Leu-2a, Leu-3a, anti-interleukin-2 receptor, and polyclonal antibodies against lysozyme and alpha 1-anti-chymotrypsin. Symptomatic onset of sarcoidosis is associated with an autologous lavage cell factor that induces intradermal epithelioid cell granulomas that are immunophenotypically similar to Kveim-induced granulomas.