Mechanisms of Hypergammaglobulinemia in Pulmonary Sarcoidosis

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Abstract
Pulmonary sarcoidosis is a disorder in which local granuloma formation is perpetuated by activated lung T lymphocytes. The present study suggests that lung T lymphocytes may also play a critical role in modulating local production of antibodies in this disorder. In untreated patients with pulmonary sarcoidosis, the numbers of IgG- and IgM-secreting cells per 103 lung lymphocytes are markedly increased compared with those in normal individuals (P < 0.001 and P < 0.01, respectively); the numbers of IgA-secreting cells in lavage fluid of these patients are not increased (P > 0.2). In contrast to lungs, the numbers of IgG-, IgM-, and IgA-secreting cells in blood of patients with this disorder are similar to those in normal individuals (P > 0.2, each comparison). In patients with pulmonary sarcoidosis, there is a direct correlation between the percentage of bronchoalveolar cells that are T lymphocytes and the percentage of bronchoalveolar cells that secrete IgG (r = 0.79; P < 0.001); in normal individuals there is no such relationship (P > 0.2). When purified sarcoid lung T cells from patients with high proportions of T lymphocytes in their lavage fluid were co-cultured with blood mononuclear cells from normal individuals (without added antigens or mitogens), the B lymphocytes in these normal mononuclear cell suspensions were induced to differentiate into immunoglobulin-secreting cells (P < 0.01). In contrast, blood T lymphocytes from these same patients and lung T lymphocytes from sarcoidosis patients with low proportions of T lymphocytes in their lavage fluid did not stimulate normal B cells to produce immunoglobulin (P > 0.2, all comparisons). These findings suggest that in pulmonary sarcoidosis (a) the lung is an important site of immunoglobulin production; (b) activated lung T lymphocytes play an important role in modulating this local production of antibody, and thus are likely to modulate the polyclonal hyperglobulinemia observed in these individuals.