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Sarcoidosis is a disease of unknown etiology characterized by granuloma formation in tissues and anergy to delayed hypersensitivity. In 34 sarcoidosis patients and 16 normal persons, T cells from peripheral blood were quantitated and their functional capacity assessed by sheep red blood cell (SRBC) rosette assay and mitogen response, respectively. Effect of Kveim-Siltzbach suspension (KSS) on rosette formation and its ability to induce blast formation were also examined. Normal spleen cell suspension (NSS) was used as control. The results show that 84% of patients had suppressed T-cell numbers, while 79% had suppression of both active (rosettes formed immediately on incubation with SRBC) and total (rosettes formed after a 1-hr incubation on ice) T cells. Mean active was 30% in sarcoidosis patients vs 44% in controls, while mean total was 48% in sarcoidosis patients vs 64% in controls, while mean total was 48% in sarcoidosis patients vs 64% in control subjects. Suppressed mitogen response to phytohemagglutinin was seen in only 34% of patients and of this number, 90% had decreased T-cell numbers (active and total), suggesting that T-cell suppression does not necessarily reflect functional abnormality in these cells; however, the reverse is true. KSS caused no blastogenesis or change in rosette formation when incubated with lymphocytes from sarcoid patients (KSS active 36%; total 48%: NSS active 34%; total 48%). Either the cells are insensitive to KSS stimulation or sensitive cells have migrated to sites of granuloma formation.

Among 80 Black patients with sarcoidosis, 11 families were identified as containing multiple cases. Monogenic modes of inheritance were reasonably excluded by informal inspection of pedigree patterns and by poor fit of corrected ratios within sibships to the expected ratio for all sibships at risk. The observed familial distribution conforms in several respects to properties that are descriptive of multigenic traits. Additionally, heritability based only on female probands was estimated to be between 60% and 70%. A larger sample size should permit analysis of additional multigenic properties.

Pulmonary granulomata of sarcoidosis are composed primarily of mononuclear phagocytic cells that are probably derived from blood monocytes. To evaluate the concept that recruitment of blood monocytes to the sarcoid lung is mediated by chemoattractants produced by immune effector cells within the lung, we obtained mononuclear cells from lung and blood of six patients with active pulmonary sarcoidosis, six normal subjects, and six patients with active idiopathic pulmonary fibrosis and studied their ability to secrete a chemotactic factor for monocytes. Lung T lymphocytes from all sarcoidosis patients, but not from normal subjects or patients with idiopathic pulmonary fibrosis, spontaneously secreted such a mediator. Lung T lymphocytes from patients with sarcoidosis secreted more monocyte chemotactic factor than did blood T lymphocytes from the same patients. The accumulation of monocytes in the lung in patients with pulmonary sarcoidosis may be mediated by local production of monocyte chemotactic factor by lung T lymphocytes.

Cellular and immunoglobulin components of bronchoalveolar fluid recovered by bronchoscopic lavage were evaluated in 32 control patients, 10 normal volunteers, and 60 patients with the following interstitial lung diseases: idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, eosinophilic granuloma, sarcoidosis, and hypersensitivity pneumonitis. The percentage of lymphocytes distinguished two general disease categories: those with increased lymphocytes (sarcoidosis and hypersensitivity pneumonitis); and those with normal lymphocytes (idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, and eosinophilic granuloma). Patients in all five disease categories had elevated IgG levels and percentages of neutrophils compared with control patients, with the highest proportion of neutrophils found in idiopathic pulmonary fibrosis. Immunoglobulin levels also helped distinguish among patient groups, in that patients with hypersensitivity pneumonitis had lavage IgG/albumin ratios greater than 1, whereas patients with sarcoidosis had ratios less than 1; and with infrequent exceptions, the finding of IgM in lavage fluid was limited to patients with hypersensitivity pneumonitis.

Alpha 1 antitrypsin levels measured by the trypsin inhibitory capacity method were increased in a group of 23 patients with active sarcoidosis not under treatment when compared with a group of 17 patients, with inactive sarcoidosis, or age and sex matched healthy controls. Twelve of these patients and two of the control subjects were also studied by the radial immunodiffusion method and cellulose acetate serum electrophoresis methods for measuring a 1 antitrypsin. Obstruction of larger airways was present in 10 of 40 sarcoidosis patients, while the remainder had either a restrictive or normal pattern. In eight patients, measurement of diffusing capacity and a closer assessment for airways obstruction was obtained with measurements of specific airway conductance, thoracic gas volumes, and static and dynamic lung compliance at several respiratory frequencies. Disease of smaller airways was present in six patients as determined by frequency dependence of their dynamic lung compliance. Since three were nonsmokers, airways obstruction was thought to be due to mechanical effects of granulomas. a 1 antitrypsin levels may be another useful determinant of disease activity and may be used to supplement other clinical and laboratory indices of activity.

In Washington, DC, 105 black patients. who had biopsy specimens which confirmed sarcoidosis, were studied clinically. Of these, 16% were asymptomatic while the remainder had a variety of respiratory, constitutional, and other manifestations in agreement with the classical concept of the disease. Twenty-nine patients were in the roentgenographic category of hilar lymphadenopathy bilaterally with or without parenchymal lung infiltration. Seventy-eight patients were anergic to skin-test antigens. Of 33 patients who were Kveim tested, only seven had abnormal biopsy specimens. Patient selection for treatment was based on disease severity. Of the original 105 patients, 64 were observed for five years. The majority improved, but five died. Prognosis was related to both roentgenographic categorization of disease as well as to clinical manifestations.